Geneva, Switzerland — March 10, 2008 — Anavex Life Sciences Corp. (“ANAVEX”) (OTCBB: AVXL) today announced that ANAVEX 7-1037 has demonstrated its ability to significantly delay the growth of cancerous tumors in patient-derived xenografts during advanced pre-clinical studies. The human tumor xenografts were developed in ANAVEX labs using a sample taken from a person suffering from clear cell sarcoma. Clear cell sarcoma is a rare type of melanoma (skin cancer) that is difficult to treat.
In comparative pre-clinical studies, ANAVEX 7-1037 reduced tumor growth by 69% with minimal side effects. Significantly, Dacarbazine, a currently available chemotherapy drug used to treat melanoma and other types of cancer, was found to be completely inactive in the same tests. ANAVEX 7-1037 is the company’s lead drug candidate for the treatment of a number of cancers, including that of the breast, colon, prostate and melanoma. It exhibits a high safety profile and disease-modifying potential.
“These results further confirm the potent, anti-cancer activity and chemotherapeutic potential of ANAVEX 7-1037, even in cancers that are difficult to treat,” said Dr. Kontzalis, Chief Executive Officer for ANAVEX. “We remain committed to developing first-class, cancer-fighting therapeutics based on our SIGMACEPTOR™ Discovery Platform, which utilizes a new class of receptor molecules known as sigma ligands to influence the origin or development of a disease.”
ANAVEX 7-1037 More Effective in Pre-Clinical Studies
During pre-clinical studies, ANAVEX 7-1037 was administered directly into the abdominal cavity of immune-deficient mice at four different dose levels (100, 70, 40 and 10mg/kg). The mice had been inoculated subcutaneously with cancerous human cells on a “five days on, two days off” schedule. ANAVEX 7-1037 was administered beginning when tumors in advanced-stage subcutaneous mice models reached approximately 250 cubic millimeters in size (day 22 post inoculation). Administration of ANAVEX 7-1037 was stopped when tumors of the control group had grown to approximately 1,000 cubic millimeters (day 33 post inoculation).
Dacarbazine was used as a control drug and was administered for five consecutive days at a dose of 80 mg/kg. Each group consisted of at least seven animals, which is equal to 14 tumors or two tumors per mouse.
Under the experimental conditions tested, the control drug Dacarbazine did not show any measurable activity against this patient-derived xenograft. In contrast, ANAVEX 7-1037 exhibited significant activity at dosage levels of 100 mg/kg. A deltaT/deltaC score of 31% was demonstrated, where T is equal to the animals treated with ANAVEX 7-1037 and C is equal to the untreated control group, meaning that tumor growth volume was reduced by 69% more in the ANAVEX 7-1037 group than in the control group. The 31% score achieved with ANAVEX 7-1037 is far better (lower) than the 42% deltaT/deltaC score standard set by the U.S. National Cancer Institute (NCI) to characterize a compound as a potent anti-cancer drug. These noteworthy results were achieved after ANAVEX 7-1037 had been administered seven times at a statistically significant level (post inoculation day of cancer cells, or p.i.d.=33, tumor size, or p<=0.001) when compared to the tumors of the untreated control mice. The 70 mg/kg dose of ANAVEX 7-1037 showed an effect on the tumors that was quite close to the NCI criterion of the 42% limit, again with the best deltaT/deltaC values (p.i.d.=33, deltaT/deltaC=45%, p=0.003) after the seventh dose of ANAVEX 7-1037 was administered. The remaining doses that were administered (at 40 and 10 mg/kg) showed a dose-dependent effect on the tumors but with no significant importance. No significant weight loss was recorded during the period of the experiment.
ANAVEX continues to conduct experiments in xenografts with a focus on melanoma and other tumors that in-vitro methodology (i.e. screening of potential candidate compounds for toxicity and efficacy using various cancer cell cultures) has suggested would respond better to the agent.
ANAVEX 7-1037 has been previously reported to exhibit high affinity for sigma-1 (nanomolar) receptors and moderate (micromolar) affinity for sigma-2 receptors and sodium channels. In addition, ANAVEX 7-1037 has been shown to induce selective apoptosis (programmed cell death) in HCT116 colon cancer cells in vitro, as detailed in a press release dated December 11, 2007.
These features of ANAVEX 7-1037 have made it one of the company’s lead compounds in its efforts to develop pioneering, new anti-cancer drugs for the treatment of solid tumors. ANAVEX 7-1037 has so far been tested in vitro against more than 20 human cancer cell lines representing different types of cancer – it has demonstrated significant in vitro tumor-growth-delaying activity against most of them, as represented by the GI50 (i.e. 50% of the dose required for tumor growth inhibition) of the compound. As such, ANAVEX 7-1037 has been advanced for testing against additional xenografts in order to further establish and confirm its potential as a potent anti-cancer drug.
ANAVEX 7-1037 is being studied for activity against a rare type of melanoma called clear cell sarcoma. Tests are performed by ANAVEX on xenografts developed directly from a sample that was surgically removed from a patient (primary/patient-derived xenografts) suffering from the disease. The patient had been treated with Dacarbazine. This study was implemented as a first step in ANAVEX’s efforts to test the activity of the compound against melanoma, as the in-vitro results suggested that the compound may be selective against certain cancer types (such as melanoma, colon, breast and prostate).
Drugs that act on the underlying cause of the disease and/or slow/reverse the progression of the disease, which have a novel mode of action that could fulfill some of the most urgent medical needs like efficacy, drug resistance, side effects, administration and affordability, are needed and have significant market potential. ANAVEX is developing drug candidates demonstrating these properties.
About Sigma Receptors
Sigma receptors are a unique family of proteins, present mainly in the central nervous system (CNS) but also in various peripheral tissues. The receptors are classified into two subtypes: the sigma-1 and sigma-2. These subtypes are distinguishable pharmacologically, functionally and by molecular size. Sigma-1 receptors have been cloned and shown to be distinct from any known receptor class.
Both sigma receptor subtypes are highly expressed in tumor cell lines from various tissues. These include neuroblastomas, glioma, melanoma and carcinoma cell lines of breast, prostate and lung. Interestingly, sigma receptors are more highly expressed in rapidly proliferating cells and are down-regulated when cells become inactive. Their high density in various tumor cell types, and particularly in proliferating cells, makes sigma receptors a potential target for diagnostic imaging as well as therapeutic agents. Recent data suggests that sigma-2 receptor agonists induce cell death in various tumor cell lines including prostate and breast carcinoma, with features consistent with apoptosis. Sigma-2 receptor agonists are reported to induce apoptosis by a novel mechanism, exhibiting similar potency in tumors with wild-type or mutant p53 gene, unlike other agents such as DNA-damaging agents. The mechanism of sigma-2 receptor-mediated apoptosis differs from that of agents that trigger DNA damage, based on observations with inhibitors of caspases. The involvement of distinct apoptotic pathways is further supported by the ability of sigma agonists to potentiate the cytotoxicity of DNA-damaging antineoplastics in various tumor cell lines.
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (www.anavex.com) is an emerging biopharmaceutical company engaged in the discovery and development of novel drug targets for the treatment of cancer and neurological diseases. The company’s proprietary SIGMACEPTOR™ Discovery Platform involves the rational drug design of compounds that fulfill specific criteria based on unmet market needs and new scientific advances. Selected drug candidates demonstrate high, non-exclusive affinity for sigma receptors, which are involved in the modulation of multiple cellular biochemical signaling pathways.
ANAVEX’s SIGMACEPTOR™-N program involves the development of novel and original drug candidates, targeting neurological and neurodegenerative diseases (Alzheimer’s disease, epilepsy, depression, etc.). The company’s lead drug candidates exhibit high, non-exclusive affinity for sigma receptors with strong evidence for anti-amnesic, neuroprotective, anti-apoptotic, anti-oxidative, anti-inflammatory, anti-convulsive, anti-depressant and anxiolytic properties.
ANAVEX 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 such as colon, prostate, breast and lung.
This press release contains forward-looking statements for Anavex Life Sciences Corp. that involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors. Among other things, there can be no assurance that any of the Company’s development efforts relating to its product candidate, Anavex 7-1037, will be successful, or such product candidate will be successfully commercialized or that Anavex 7-1037 will have the potential to treat melanoma, colon cancer or other types of human cancer or that Anavex 7-1037 will provide clinically relevant advantages over other competitive compounds in development or that sigma ligands will have the potential to be a new class of drugs to treat colon cancer or other types of human cancer. Other risks that affect forward-looking information contained in this press release include the high degree of risk associated with drug development, results of further research and development, the impact of competition and of technological advances and other risks detailed to Anavex’s SEC filings. Other than as required by federal securities laws, we undertake no obligation to publicly update or revise any of our forward-looking statements, whether as a result of changed circumstances, new information, future events, or for any other reason occurring after the date of this news release.
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