Axonyx Expands Scope of Phenserine Beta Amyloid Clinical Trial in Alzheimer's Disease; Sub-Study To Include Brain Scans To Measure Disease Progression.

Business Editors

NEW YORK--(BUSINESS WIRE)--Dec. 19, 2003

Axonyx Inc. (NASDAQ:AXYX) today announced that as a result of the high-level scientific input during the recently held symposium "Alzheimer's Disease: Modification and Measurement", as well as the guidance received from the Axonyx Steering Committee that oversees the ongoing clinical trials with Phenserine, the company will now broaden its ongoing Phenserine Phase IIB clinical study and include a sub-study that will use brain scans of Alzheimer's disease (AD) patients to assess disease progression. The ongoing Phase IIB clinical study is designed to evaluate Phenserine's ability to lower the levels of the beta-amyloid precursor protein (B-APP) and Amyloid beta (AB) in the plasma and cerebrospinal fluid of mild-to-moderate AD patients. A reduction of these protein levels may result in the slowing of the progression of AD. Phenserine, a dual acetylcholinesterase and B-APP inhibitor, has previously been shown to be safe and efficacious in improving the memory of mild-to-moderate AD patients in a 12-week study. Phenserine is currently also in a Phase III clinical trial designed to confirm these memory improvement effects in mild-to-moderate AD patients. The progress of the Phase III study is on target for completion by the end of 2004.

Axonyx intends to add a sub-study to its Phenserine Phase IIB AB clinical study by including Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) brain scans to assess the potential effect of Phenserine on certain brain structures and metabolism that are known to be involved in AD. The invasive nature associated with the ongoing Phase IIB study has led to a recent slowing of the rate of patient recruitment and advantage will be taken of this to have the remaining patients also participate in the brain scan sub-study. The sub-study protocol will be finalized and suitable clinical sites will be engaged to participate as soon as possible. In addition, as the exact extent to which Phenserine will effect the levels of AB in the cerebrospinal fluid of individual AD patients is unknown, the Axonyx Steering Committee has advocated a blinded data review to be undertaken in February 2004 that will serve to confirm the initial statistical assumptions that were made for the main Phase IIB AB trial. The result of this analysis may or may not require additional patients to be recruited.

The presence and accumulation of toxic beta-amyloid in the brains of AD patients are considered by many experts to be key pathological events in the causation as well as the progression of AD. PET can detect and potentially quantify the accumulation of AB, including its consequent metabolic effects on glucose metabolism. Alzheimer's disease brain pathology is also associated with typical structural changes in the brain that include the formation of amyloid plaques, neurofibrillary tangles and finally the death of nerve cells that are necessary for normal memory and cognitive function. These so-called morphological changes can lead to very subtle shrinkage, known as atrophy, of the relevant brain areas that can be detected by high resolution MRI. Recent advances in both PET and MRI have led to highly specific and sensitive techniques that may detect the effect of Phenserine treatment on the brains of AD patients.

Due to the time required to set up and gain the necessary approvals for this sub-study, as well as the potential need for additional patients, Axonyx recognizes that these decisions will have an effect on the timeline of the study and it is anticipated that the results will now not be available before the end of 2004. However, Axonyx believes that this is an important study for Alzheimer's patients and Phenserine and every effort should be made to examine Phenserine's unique dual mechanism of action that has been shown to improve memory and may potentially modify AD progression as well. Phenserine's ability to reduce the levels of AB through its effects on B-APP may also result in detectable changes in brain structures and metabolism that are believed to be involved in AD.

"We are very encouraged by the advances made by various scanning techniques that correlate brain structures and metabolism to Alzheimer's disease" stated Professor Bengt Winblad, Professor of the Department of Geriatric Medicine at the Karolinska Institute and Chief Physician at the Huddinge Hospital in Stockholm, Sweden. "The data on Phenserine's potential ability to modify AD progression may translate into important findings related to brain structures and metabolism in patients," Professor Winblad added.

"Axonyx is committed to validating in the Alzheimer's patient the overwhelming preclinical data that has shown a reduction in the levels of beta amyloid," stated Gosse B. Bruinsma MD, President and COO. "We feel that the urgent need for a treatment that could slow the disease progression warrants every effort to detect and quantify Phenserine's ability to do this by using these latest brain imaging technologies."

The Axonyx Steering Committee oversees Phase IIb and Phase III clinical trials with Phenserine for Alzheimer's disease (AD). Professor Bengt Winblad serves as Chairman of the committee, Professor Ezio Giacobini of the University of Geneva, Switzerland and Professor Dr. Lutz Frolich of the University of Heidelberg, Germany are also members. The Steering Committee monitors the conduct and progress of the Phase IIb beta-amyloid trial, as well as the potentially pivotal Phase III clinical trial that will evaluate the safety and efficacy of Phenserine treatment in mild-to-moderate AD patients.

About Axonyx

Axonyx Inc. is a U.S.-based biopharmaceutical company engaged in the acquisition and development of proprietary pharmaceutical compounds and new technologies useful in the diagnosis and treatment of Alzheimer's disease, human memory disorders and prion-based illnesses such as Mad Cow disease. Its leading Alzheimer's disease drug candidate is Phenserine, a dual action acetylcholinesterase and beta amyloid precursor protein (B-APP) inhibitor, and currently in Phase IIB and Phase III clinical trials. A previously completed Phase II trial showed that Phenserine was well tolerated and effective in improving the memory of mild-to-moderate AD patients.

The ongoing Phase IIB clinical study is designed to evaluate Phenserine's ability to lower the levels of the beta-amyloid precursor protein (B-APP) and Amyloid beta (A-B) in the plasma and cerebrospinal fluid of mild-to-moderate AD patients. The presence of toxic beta-amyloid in the brains of AD patients is considered by many experts to be a key pathological event in the causation as well as the progression of AD. A reduction of these levels may be able to slow the progression of AD.

This press release may contain forward-looking statements or predictions. These statements represent our judgment to date, and are subject to risks and uncertainties that could materially affect the Company including those risks and uncertainties described in the documents Axonyx files from time to time with the SEC, specifically Axonyx's annual report on Form 10-K. Axonyx cannot assure that the Phase IIB and/or the Phase III clinical trial, or others, if any, with Phenserine will prove successful, that the safety and efficacy profile of Phenserine exhibited in the previous small Phase II trial will remain the same in the Phase IIB and Phase III clinical trials, or future clinical trials, if any, that the preclinical results related to the regulation of beta-APP will be substantiated by the Phenserine Phase IIB clinical trial and that Phenserine will be able to slow the progression of Alzheimer's disease, that the Phase IIB clinical trial data will differentiate Phenserine from the currently marketed drugs, that the efficacy results of the Phase III trial will prove pivotal, that the efficacy data from the Phase IIB clinical trial will be able to be used in the Phase III trial efficacy data, that Axonyx will obtain the necessary financing to complete the Phase III Phenserine trials, that the Company's development work on Phenserine will support an NDA filing, that the results of the Phase III trials will allow Phenserine to be approved by the FDA, that the FDA will grant marketing approval for Phenserine, that if Phenserine is approved by the FDA, it will prove competitive in the market, and that Axonyx will obtain licensing or corporate partnership agreements that will enable acceleration of the development of and optimize marketing opportunities for, Phenserine, or that Axonyx will be able to advance any other potential memory enhancing compound toward IND status. Axonyx undertakes no obligation to publicly release the result of any revisions to such forward-looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.