• Alzheimer’s disease – In 2014, an estimated 5.2 million Americans are suffering from Alzheimer’s disease. The Alzheimer’s Association® reports that by 2025, 7.1 million Americans will be afflicted by the disease, a 40 percent increase from currently affected patients. Medications on the market today treat only the symptoms of AD and do not have the ability to stop its onset or its progression. There is an urgent and unmet need for both a disease modifying cure for Alzheimer’s disease as well as for better symptomatic treatments.
   

• Depression – Depression is a major cause of morbidity worldwide according to the World Health Organization (WHO). Pharmaceutical treatment for depression is dominated by blockbuster brands, with the leading nine brands accounting for approximately 75% of total sales. However, the dominance of the leading brands is waning, largely due to the effects of patent expiration and generic competition. Our market research leads us to believe that the worldwide market for pharmaceutical treatment of depression exceeds $11 billion annually.
   

• Epilepsy – Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or synchronous neuronal activity in the brain. According to the Centers for Disease Control and Prevention, epilepsy affects 2.2 million Americans. Today, epilepsy is often controlled, but not cured, with medication that is categorized as older traditional anti-epileptic drugs and second generation anti-epileptic drugs. Because epilepsy afflicts sufferers in different ways, there is a need for drugs used in combination with both traditional anti-epileptic drugs and second generation anti-epileptic drugs. Decision Resources, one of the world’s leading research and advisory firms for pharmaceutical and healthcare issues, finds that the epilepsy market will increase from $2.9 billion in 2011 to nearly $3.7 billion in 2016.
   

• Neuropathic Pain – We define neuralgia, or neuropathic pain, as pain that is not related to activation of pain receptor cells in any part of the body. Neuralgia is more difficult to treat than some other types of pain because it does not respond well to normal pain medications. Special medications have become more specific to neuralgia and typically fall under the category of membrane stabilizing drugs or antidepressants. Our market research leads us to believe the worldwide market for pharmaceutical treatment of neuropathic pain exceeds $5 billion annually.
   

• Malignant Melanoma – Predominantly a skin cancer, malignant melanoma can also occur in melanocytes found in the bowel and the eye. Malignant melanoma accounts for 75% of all deaths associated with skin cancer. The treatment includes surgical removal of the tumor, adjuvant treatment, chemo and immunotherapy, or radiation therapy. According to IMS Health the worldwide malignant melanoma market is expected to grow from about $900 million in 2012 to $4.4 billion by 2022.
   

• Prostate Cancer – Specific to men, prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. The cancer cells may metastasize from the prostate to other parts of the body, particularly the bones and lymph nodes. Drug therapeutics for prostate cancer are expected to increase from $8.1 billion in 2012 to nearly $18.6 billion in 2017 according to BCC Research.
   

• Pancreatic Cancer – Pancreatic cancer is a malignant neoplasm of the pancreas. In the United States approximately 45,000 new cases of pancreatic cancer will be diagnosed this year and approximately 38,000 patients will die as a result of their cancer. Our market research leads us to believe that the market for the pharmaceutical treatment of pancreatic cancer will exceed $1.2 billion by 2015.
  
  
   
• 

   

  Christopher U. Missling, MS, PhD, MBA

   

  Dr. Missling, President and CEO of Anavex, has over 20 years of healthcare industry experience within large pharmaceutical companies, the biotech industry and investment banking. Prior to joining Anavex, he served as the Chief Financial Officer of Curis and ImmunoGen. In addition, at Aventis (now Sanofi), Dr. Missling worked as head of financial planning on all aspects of financial strategy and M&A. His career experience also includes working as an investment banker in the healthcare practice at Deutsche Bank, serving pharmaceutical, biotech, and diagnostic companies, as well as serving as the head of healthcare investment banking at Brimberg & Co. in New York. Dr. Missling has an MS and PhD from the University of Munich in Chemistry and an MBA from Northwestern University Kellogg School of Management.

  Tasos Zografidis, MS, PhD

  Dr. Zografidis, the Vice President Clinical Operations of Anavex, has over 25 years of experience in the pharmaceutical and healthcare industry, including 12 years at Wyeth (now Pfizer) in clinical project management and prior to joining Anavex most recently served as clinical and pharmaceutical consultant. He has been involved in more than a dozen clinical trials and has co-authored numerous publications. At Wyeth, Dr. Zografidis spearheaded population pharmacokinetics analysis and its implementation in the clinical setting and positively differentiated compounds. His work resulted in increased sales and he received several clinical awards for his accomplishments. Dr. Zografidis first joined Wyeth in 1998 as a Product Manager. During his tenure until 2010, he had increased responsibility as Medical Liaison for the transplantation, haemophilia and oncology divisions where he was instrumental in driving sales in assigned European territories.

  Bernd Metzner, PhD

  Bernd Metzner, PhD, a director of Anavex, is currently Chief Financial Officer of the Doehler Group, a global producer and provider of technology-based natural ingredients for the food and beverage industry with sales activities in more than 130 countries. Previously, he was Chief Administration Officer and member of the Board of Management of Bayer Schering Pharma AG, the pharmaceutical division of $100+ billion market cap company Bayer AG. In this position, Dr. Metzner had worldwide financial responsibility for the Bayer Pharma Group. During his almost 10-years with Bayer AG, Dr. Metzner also held several senior international management positions in the corporate finance organization of Bayer AG, including Chief Financial Officer of Bayer S.p.A. Italy and heading the coordination of the successful spin-off of Lanxess, a specialty chemicals group. Dr. Metzner started his career at the law firm Flick Gocke Schaumburg and has a degree in business administration from the University of Siegen. After obtaining his doctorate, he became a chartered accountant.

  Elliot Favus, MD

  Elliot Favus, MD, a director of Anavex, is Chief Executive Officer of Favus Institutional Research, a healthcare research firm serving institutional investors. He has been a healthcare equity research analyst on Wall Street since 2006, starting at Lazard Capital Markets and subsequently at Och-Ziff Capital Management Group. Prior to working on Wall Street, Dr. Favus was an Instructor in medicine at Mount Sinai School of Medicine in New York. He attended the University of Michigan (BA, 1996), the University of Chicago Pritzker School of Medicine (MD, 2001) and the NYU-Bellevue Hospital Internal Medicine Residency Program (2004). He is board-certified in Internal Medicine (2004) and has 10 years of basic science laboratory experience working on human genetics projects at Harvard Medical School, the University of Chicago and the University of Pittsburgh.

  Tom Skarpelos

  Mr. Skarpelos, a director of Anavex, is a self-employed investor with 17 years of experience working with private and public companies. For the past 10 years, he has been focused on biotechnology companies involved in drug discovery and drug development projects.Mr. Skarpelos was engaged as a consultant to Anavex Life Sciences for one year effective August 2, 2010. His experience has led to relationships with researchers at academic institutes in Europe and North America. Mr. Skarpelos is a founder of Anavex Life Sciences, and is its largest shareholder.

  Steffen Thomas, PhD

  Steffen Thomas, PhD, a director of Anavex, has over 15 years of experience as a European patent attorney and is currently practicing at Epping Hermann Fischer, a major intellectual property law firm in Europe. Previously, he worked for Japan-based Takeda Pharmaceutical Company, the largest pharmaceutical company in Asia and a top firm worldwide, as an in-house patent attorney. Prior to that, he worked for Nycomed Pharma, acquired by Takeda in 2011 for approximately USD $10 billion.  Dr. Thomas’ legal practice covers drafting of patent applications, prosecuting patent applications before national and international patent offices, defending and challenging patents in opposition, appeal, and nullity proceedings, enforcing patents before the infringement courts, and preparing opinions on patentability and infringement in the technical field of chemistry.  Dr. Thomas has particular expertise in small molecule pharmaceuticals.  He holds MS and PhD degrees in Chemistry from the University of Munich.

  Abraham Fisher, PhD

  A member of the Scientific Advisory Board, Dr. Fisher has nearly 40 years of experience in drug design and discovery.  He has taken lead compounds including AF102B (EVOXAC®, cevimeline HCl) from concept to approval.  AF102B is the first muscarinic agonist approved for sale in the U.S. (2000) and in Japan (2001) to treat dry mouth in patients with Sjoergen’s Syndrome. Dr. Fisher is also the inventor of AF710B (renamed ANAVEX 3-71).  Dr. Fisher is co-founding Chairman and President of the Alzheimer’s and Parkinson’s Diseases Conference,is on the scientific review board of the Alzheimer’s Drug Discovery Foundation and is a reviewer of the Alzheimer’s Association.  He is named on 21 patents worldwide, is the author of numerous peer-reviewed papers and academic book chapters and is associate editor of Current Alzheimer Research.  He also serves on the editorial board of Neurodegenerative Diseases and was on the editorial boards of CNS Drug Reviews, Japanese Journal of Pharmacology and Drug Development Research.  Currently Dr. Fisher is a visiting professor at the Department of Neurobiology at the Weizmann Institute in Israel.  Previously he was senior scientist at the Israel Institute for Biological Research (IIBR) and held faculty appointments as adjunct professor in the Departments of Pharmacology and Psychiatry, Southern Illinois University and in the School of Medi­cine, Department of Molecular and Cellular Pharmacology, University of Miami.

  Norman Relkin, MD, PhD

  A member of the Scientific Advisory Board, Dr. Relkin is an internationally recognized expert on Alzheimer’s disease and related disorders. An American Board of Psychiatry and Neurology-certified neurologist, he graduated from Yale and earned MD and PhD degrees from New York’s Albert Einstein College of Medicine. Dr. Relkin is an Associate Professor of Neurology at the Weill Cornell Medical College and Founding Director of the Weill Cornell Memory Disorders Program. He has 20+ years of clinical trials experience, serving as principal investigator in over 20 therapeutic studies, including multi-center trials he designed. Over the past decade, Dr. Relkin pioneered the study of naturally occurring human antibodies for the treatment of Alzheimer’s. He led all three clinical trial phases of Intravenous Immunoglobulin as a potential Alzheimer’s treatment, including the pivotal National Institutes of Health (NIH) and Baxter co-sponsored study carried out at 45 sites (US and Canada). The author of numerous publications on neurodegenerative and traumatic disorders of the brain during the past 25 years, Dr. Relkin sits on editorial boards for three scientific journals. Additionally, he has been a reviewer for NIH and funding agencies in Europe and Australia, and has been a long-standing member of the Weill Cornell Institutional Review Board. In 2012, he was elected to the Board of Directors of The American Federation for Aging Research.

  Michael Gold, MD

  A member of the Scientific Advisory Board, Dr. Gold has over 20 years of experience in the clinical development of Alzheimer’s and other central nervous system (CNS) drugs, and currently serves as Vice President of the CNS practice at UCB, Inc., a global biopharmaceutical company. His background also includes leadership roles with GlaxoSmithKline (GSK), Johnson & Johnson (J&J) and Bristol-Myers Squibb (BMS). At GSK, Dr. Gold was responsible for the late-stage CNS and pain portfolio. He also led several clinical Phase II and Phase III Alzheimer’s disease-related project teams. At J&J, Dr. Gold served as the Compound Development Team Leader for Galantamine, an Alzheimer’s drug, culminating in FDA approval of Galantamine CR (Razadyne® ER). Prior to joining UCB, Dr. Gold served as the Chief Medical Officer of Allon Therapeutics, where he led a large pan-US and European clinical study for a neurodegenerative disease. Before joining the pharmaceutical industry, Dr. Gold was an Assistant Professor at the University of South Florida (USF) College of Medicine Department of Neurology and Director of the USF Memory Disorders Clinic. During this time, he was the Principal Investigator for several clinical trials for Alzheimer’s disease. He has also authored multiple publications related to Alzheimer’s and dementia. Dr. Gold also holds an academic appointment as an adjunct assistant professor in the Department of Medicine at the University of North Carolina at Chapel Hill.

  John Harrison, PhD

  A member of the Scientific Advisory Board, Dr. Harrison is an internationally acknowledged specialist for design of human clinical outcome measurement in Alzheimer’s disease and other cognitive impairments. Dr. Harrison has successfully integrated cognitive testing into drug development programs for many pharmaceutical and biotechnology companies including eight of the current ‘Fortune’ top 10 pharmaceutical companies. He is Honorary Senior Lecturer in the Department of Medicine at Imperial College in London, focusing on investigating cognitive change that may show disease progression in Alzheimer’s and other related indications. Dr. Harrison is a member of the American Psychological Association, holds Chartered Psychologist status with the British Psychological Society and Chartered Scientist status with the UK Science Council. He has authored/co-authored more than 60 books and scientific articles and has been invited as a specialist for cognitive tests at many international meetings, including the European Task Force for Alzheimer’s disease and American Alzheimer’s Association roundtable events. Dr. Harrison’s background also includes prior positions as Head of Neuropsychology at CeNeS Pharmaceuticals, Principal Consultant at CPC Pharma Services, and Principal Scientist at CogState Ltd. In addition to his current academic appointment, he is principal consultant at Metis Cognition Ltd and holds a PhD in neuroscience from the University of London.

  Ottavio Arancio, MD, PhD

  A member of the Scientific Advisory Board, Dr. Arancio is a cellular neurobiologist who has pioneered the field of mechanisms of synaptic dysfunction in Alzheimer’s disease. He is Associate Professor of Pathology and Cell Biology at the Columbia University Medical Center and The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University. Over the last 10 years, Dr. Arancio has raised more than $25 million in grant funding and published more than 100 peer-reviewed scientific papers. Dr Arancio’s honors include the “G. Moruzzi Fellowship” (Georgetown University), the “Anna Villa Rusconi Foundation Prize” (Italy), the “INSERM Poste vert Fellowship” (France), the Edward N. and Della L. Thome Memorial Foundation Award (2010), the Margaret Cahn Research Award (2008), the American Health Assistance Foundation Centennial Award (2007) and the Zenith Award (2007). He also founded Citta Pharmaceuticals, a biotech company for development of small molecules to treat Alzheimer’s disease.

  Tangui Nicolas Maurice, Ph.D.

  A member of the Scientific Advisory Board, Dr. Maurice has spent 15 years in the field of neurosciences, including behavioral and molecular neuropharmacology, sigma receptors, neuropeptides, neurosteroids, neurotrophic factors, normal/pathological aging models for Alzheimer’s and related disorders, and behavioral phenotyping of rodent models. Dr. Maurice is a researcher at the Institut national de la sante et de la recherche medicale (INSERM) U710 at Montpellier. He has also held research positions at the Centre National de la Recherche Scientifique (CNRS), INSERM U336, the department of neuropsychopharmacology and hospital pharmacy at Meijo University (Nagoya, Japan), and Jouveinal Research Institute (Fresnes, France).

  Jeffrey Cummings, MD

  A clinical expert on the Anavex Scientific Advisory Board, Dr. Jeffrey Cummings is Professor of Neurotherapeutics and Drug Development in the Neurological Institute, Cleveland Clinic. He is Director of the Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada and Cleveland, Ohio. Dr. Jeffrey Cummings graduated magna cum laude from the University of Wyoming, Laramie and obtained his MD degree (with thesis) from the University of Washington, Seattle. He completed internship at Hartford Hospital in Hartford, Connecticut and did his Neurology residency at Boston University, Boston, Massachusetts. Dr. Cummings was formerly the Augustus S. Rose Professor of Neurology and Professor of Psychiatry and Biobehavioral Sciences at the David Geffen School of Medicine at UCLA, Los Angeles, California, USA. He was the Director of the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA and Director of the Deane F. Johnson Center for Neurotherapeutics at UCLA. Dr. Cummings has expertise in neuropsychiatric assessment, outcomes in clinical trials, clinical trial design and analysis, and global clinical trials. He is a frequent consultant to industry. Dr. Cummings has authored more than 500 peer-reviewed papers and 30 books on Alzheimer’s disease, neuropsychiatry, and clinical trials. Dr. Cummings’ interests embrace the neuropsychiatry of neurologic disorders, biomarkers for neurodegenerative diseases, and clinical trials and drug development for neurologic diseases.

  Paul Aisen, MD

  A clinical expert on the Anavex Scientific Advisory Board, Dr. Aisen is a leading clinician and researcher in Alzheimer’s disease clinical trials and is on the faculty of the University of California, San Diego (UCSD) School of Medicine’s Department of Neurosciences. His primary research interests focus on the development of new strategies for the treatment of Alzheimer’s disease. Since 2007, Dr. Aisen has been Director of the Alzheimer’s Disease Cooperative Study, a consortium funded by the National Institute on Aging (NIA) to develop assessment instruments and conduct clinical trials. Dr. Aisen is Associate Editor of Alzheimer’s Research and Therapy, a major international peer-reviewed journal, and sits on the editorial board of BMC Medicine. He has published more than 180 peer-reviewed papers.

  Corinne Lasmézas, DVM, PhD

  A member of the Scientific Advisory Board, Professor at The Scripps Research Institute for the past 10 years and frequent TED Speaker, Dr. Lasmézas is an internationally recognized expert in the field of neurodegenerative diseases with a focus now on studying the mechanisms of neurodegeneration.  Since her appointment at Scripps in 2005, Dr. Lasmézas has focused on how misfolded proteins lead to neuronal dysfunction and loss in diseases including Alzheimer’s, Parkinson’s and prion diseases. Additionally, Dr. Lasmézas is a reviewer for national and private funding agencies worldwide, including the US National Institutes of Health (NIH) and the UK Medical Research Council, and an advisor for the US Food and Drug Administration (FDA), the US Environmental Protection Agency (EPA) and the US Department of Agriculture (USDA).  She has published more than 60 original scientific papers.  Earlier in her career, Dr. Lasmézas’ research provided the first experimental evidence that the prion disease “mad cow disease” had been transmitted to humans, causing variant Creutzfeldt-Jakob disease.  This fatal disease belongs to the same group of age-related neurodegenerative diseases as Alzheimer and Parkinson’s diseases, caused by aggregates of misfolded proteins.  At the peak of the mad cow crisis, Dr. Lasmézas became an advisor to the World Health Organization (WHO) as well as several governmental and public health committees.  Dr. Lasmézas holds a PhD in Neurosciences from the University Pierre & Marie Curie in Paris and obtained her Doctorate of Veterinary Medicine and Diploma of Aeronautic and Space Medicine from the University of Toulouse, France.

  Jacqueline French, MD, FAAN

  A member of the Scientific Advisory Board, professor in the Department of Neurology at New York University (NYU), Co-Director of Epilepsy Research and Clinical Trials at NYU’s Comprehensive Epilepsy Center and Director of the Epilepsy Study Consortium, Dr. French is an award-winning, internationally recognized expert on epilepsy, new therapeutic interventions and clinical trial methodology.  She plays an ongoing leadership role in the area of development of new therapeutics for epilepsy, including co-directing a bi-annual symposium on trial design and its implications and holds positions on committees of the American Academy of Neurology (AAN), where she has also co-authored several AAN clinical practice guidelines.  Broadly published, including numerous research articles, editorials and chapters, her writings have been featured in respected publications including The New England Journal of Medicine, Neuron, Neuro Image, Epilepsy Currents and Lancet Neurology.  She has also edited two books on epilepsy and is an in-demand global speaker on antiepileptic drug therapeutics and related topics.  Previously, Dr. French was Assistant Dean for Clinical Trials at the University of Pennsylvania, a recent President of the American Epilepsy Society, Secretary of the American Society of Experimental Neurotherapeutics, and worked with the US Food and Drug Administration (FDA) developing new trial designs for the approval of antiepileptic drugs.  Dr. French trained in Neurology at Mount Sinai Hospital (New York), and did her fellowship training in EEG and epilepsy at Mount Sinai Hospital and Yale University.  She was the recipient of the Epilepsy Foundation’s 2013 Hero of Epilepsy Award, honoring her longtime contributions to epilepsy research and clinical trials, alongside her significant impact on the epilepsy community.

   

   

ANAVEX PLUS shows a highly encouraging synergistic effect in Alzheimer’s disease models, producing up to 80% greater reversal of memory loss and neuroprotection when used in combination, versus when the drugs were administered individually.

The drug combination candidate might have a lower clinical trial risk because donepezil (Aricept®) is already FDA approved and on the market.

ANAVEX PLUS also represents a compelling commercial opportunity because donepezil (Aricept®) is now generic. A patent application filed for the combination would, if granted, provide protection until 2033.

Additional Study Data

Results  from a computer simulation model of Alzheimer’s presented at the CNS Summit 2013 (November 2013) confirmed the significant synergy previously seen between ANAVEX 2-73 and donepezil (Aricept®) in a pre-clinical model.

The findings in a humanized calibrated realistic cortical network computer model of Alzheimer’s disease predict that combining ANAVEX 2-73 with low dose (5mg) donepezil (Aricept®) will show up to 7 points improvement in Alzheimer’s Disease Assessment Scale–Cognitive (“ADAS-Cog”) at 12 weeks and up to 5.5 points at 26 weeks in mild-to-moderate Alzheimer’s patients, respectively.

These improvements might suggest the effects will likely be clinically detectable and meaningful.

Human clinical trials

Anavex initiated a Phase 2a trial with ANAVEX 2-73 and ANAVEX PLUS in Q4 2014.

Thereafter, the Company plans to initiate a potentially pivotal six-month Phase 2 trial with ANAVEX PLUS. This trial is expected to include up to 300 mild-to-moderate Alzheimer’s patients.

Clinical trials are conducted by third-party organizations, not by Anavex directly. Trial participants are selected independently of the company to avoid undue influence.

Note: Individuals seeking information about participating in a clinical trial should contact his/her doctor.

Patent application

Anavex has filed a patent application for the ANAVEX PLUS combination of donepezil (Aricept®) and ANAVEX 2-73. If granted, patent protection for ANAVEX PLUS will be in place until at least 2033.

 

ANAVEX 2-73 is an orally available drug candidate developed to potentially modify Alzheimer’s disease rather than temporarily address its symptoms. It has a clean Phase 1 data profile and shows reversal of memory loss (anti-amnesic properties) and neuroprotection in several models of Alzheimer’s disease.

 

Successful Phase 1 Clinical Trial

A Phase 1 single ascending dose human clinical trial of ANAVEX 2-73 was successfully completed in healthy human volunteers. It was a randomized, placebo-controlled study. Healthy male volunteers aged 18 to 55 received single, ascending oral doses over the course of the trial. The trial objectives were to define the maximum tolerated dose, assess pharmacokinetics (PK), clinical and lab safety.

Results:

• Dosing from 1-60 mg.
• Maximum tolerated dose 55-60 mg; above the equivalent dose shown to have positive effects in mouse models of Alzheimer’s disease.
• Well tolerated below the 55-60 mg dose with only mild adverse events in some volunteers.
• Observed adverse events at doses above the maximum tolerated single dose included headache and dizziness, which were moderate in severity and reversible. These side effects are often seen with drugs that target central nervous system (CNS) conditions, including Alzheimer’s disease.
• No significant changes in blood safety measurements.
• No changes in ECG.
• Favorable PK profile.
  • Rapid absorption into blood.
  • Dose proportional kinetics.

The trial was conducted in Germany by ABX-CRO in collaboration with the Technical University of Dresden. ABX-CRO and the Technical University of Dresden are well regarded for their experience with clinical trials and CNS compounds.