AVANIR's Anthrax Antibodies Have Unique Mechanism of Action and Bind to Atypical Domains of the Toxin



   Antibodies May Provide New Option to Vaccines and Antibiotics for
           the Prevention and Treatment of Anthrax Exposure

SAN DIEGO--(BUSINESS WIRE)--Dec. 2, 2003-- AVANIR Pharmaceuticals (AMEX: AVN) presented positive new data on its panel of human antibodies against the key toxin of the Class A biowarfare agent anthrax at the IBC Antibody Engineering Meeting being held this week in San Diego. Two of AVANIR's most potent anthrax antibodies, AVP 21D9 and AVP 22G12, appear unique both in mechanism of action and in terms of the binding site on the anthrax toxin.

AVP 21D9 and AVP 22G12 completely inhibit toxin complex assembly, and do so by attaching to distinct domains of the toxin. The antibodies bind to the anthrax toxin with a very high affinity, in the picomolar range. Additionally, these are two of AVANIR's most potent anthrax toxin neutralizing antibodies, exhibiting neutralizing potency in the stoichiometric range. Also notable in terms of potency, a third antibody, AVP 1C6, inhibits the anthrax toxins through a mechanism that involves the blockade of host cell receptor recognition, a more commonly used approach.

"AVP 21D9 and AVP 22G12 disrupt the assembly of the anthrax toxin, rendering it incapable of entering cells," noted Dr. Angray Kang, AVANIR's associate director of Antibody Technology. "To our knowledge, no other companies working in this area have demonstrated that their antibodies neutralize anthrax toxins by targeting this step. In addition to antibodies with this unique mechanism, we also have antibodies that are very potent but have mechanisms of action similar to the approach being developed by other companies. We feel this wide array of choices is advantageous and is due to the prolific nature of our Xenerex(TM) antibody technology."

Two posters at the 14th IBC Antibody Engineering Meeting: "Characterization of a Panel of Potent Anthrax Toxin Neutralizing Human Monoclonal Antibodies from Immunized Donors Derived by Xenerex(TM) Technology" and "Human Monoclonal Antibodies from Immunized Donors Derived by Xenerex(TM) Technology are Protective against Anthrax Lethal Toxin In Vivo" presented by Dr. Fei Wang and Dr. Ritsuko Sawada-Hirai respectively, illustrate the potency and the molecular mechanism by which these antibodies inactivate the anthrax toxins.

About AVP 21D9

AVP 21D9 is one of a panel of human monoclonal antibodies discovered and developed by AVANIR Pharmaceuticals using its Xenerex(TM) technology. Preclinical research to date demonstrates that a single dose of AVP 21D9 completely protects rats subsequently challenged with a lethal dose of recombinant anthrax toxins one week later. AVP 21D9 is a potent inhibitor of protective antigen (PA) transition to the PA multimer.

Anthrax fatalities are caused by the irreversible effects of the toxins produced by the spore-forming bacteria, Bacillus anthracis, once it enters the body. Protective antigen is a component of the anthrax toxins that plays a pivotal role in providing a portal for lethal factor (LF) and edema factor (EF) to enter into the intracellular compartment and exert a lethal effect. By neutralizing PA, AVP 21D9 effectively prevents the anthrax LF and EF toxins from entering the cells.

With AVP 21D9, AVANIR has bridged the gap between antibiotic use and conventional vaccination. In contrast to the anthrax vaccine, the protection afforded by a single dose of AVP 21D9 would be immediate. In contrast to antibiotics, AVP 21D9 acts against the key gateway component, PA, of the anthrax toxin. Although speculative, AVP 21D9 may also play a role in the prevention and treatment of infections by antibiotic-resistant strains of anthrax. Therefore, AVP 21D9 could potentially be utilized in multiple scenarios, augmenting vaccination and/or antibiotic therapy or in a stand-alone prophylaxis or therapeutic modality.

AVP 21D9 is currently in preclinical development for use as a prophylactic and therapeutic drug to treat anthrax infections. AVP 21D9 will be further evaluated in rabbits and nonhuman primates studies using B. anthracis spore challenges. Ultimately AVANIR plans to file an Investigational New Drug application seeking clearance from the U.S. Food and Drug Administration (FDA) to begin clinical trials to evaluate the safety, tolerability, and pharmacology of AVP 21D9 in healthy human subjects.

Current Anthrax Antidotes

Currently, two options are available for the prevention or treatment of anthrax exposure, a vaccine and antibiotics. Both approaches have limitations. The current anthrax vaccine may take several weeks following the first doses before immunity is established, and requires multiple injections over a period of eighteen months, in addition to an annual booster injection, to maintain its putative protective effect. This may be adequate for "preparedness" in the armed forces, or for first line responders, but is of limited use to the civilian population. Alternatively, antibiotics, the standard treatment of anthrax infection, are effective in killing anthrax bacteria, but are usually only effective when given immediately after exposure or upon suspicion of exposure to anthrax. Antibiotics are of limited use once the anthrax toxins are released. Moreover the natural emergence or deliberate release of antibiotic-resistant strains of anthrax is an ongoing concern.

About the Company

AVANIR Pharmaceuticals is a drug discovery and development company focused on the development of treatments for central nervous system disorders and inflammatory diseases. The company's first commercialized FDA-approved product, Abreva(R), is marketed in North America by GlaxoSmithKline and is the leading over-the-counter product for the treatment of cold sores. The company's lead product candidate, Neurodex(TM), is in Phase III clinical development for pseudobulbar affect and in Phase II clinical development for neuropathic pain. An internally developed small molecule, AVP 13358, is in a Phase I clinical trial for the treatment of allergy and asthma. Using its proprietary Xenerex(TM) technology, AVANIR also develops human monoclonal antibodies for infectious diseases and other therapeutic applications. Further information about AVANIR can be found at www.avanir.com.

Except for the historical information presented herein, matters discussed in this press release contain forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Statements that are not historical facts, including statements that are preceded by, followed by, or that include such words as "estimate," "anticipate," "believe," "plan" or "expect" or similar statements are forward-looking statements. Risks and uncertainties for AVANIR Pharmaceuticals include risks associated with product discovery and development as well as risks shown in AVANIR's most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q and from time-to-time in other publicly available information regarding the company. Copies of such information are available from AVANIR upon request. Such publicly available information sets forth many risks and uncertainties related to AVANIR's business and technology. The Xenerex(TM) monoclonal antibody technology competes with several technologies used by large pharmaceutical and biotechnology companies and is subject to a number of uncertainties, including risks associated with the success of clinical trials, the progress of research and product development programs, the regulatory approval process, competitive products and future capital requirements. There can be no assurance that such development efforts will succeed, that such products will receive required regulatory clearance, or that even if such regulatory clearance were received, that such products would ultimately achieve commercial success. The company disclaims any intent or obligations to update these forward-looking statements.

CONTACT: AVANIR Pharmaceuticals, San Diego
Investor Relations:
Patrice Saxon, 858-622-5202
psaxon@avanir.com

SOURCE: AVANIR Pharmaceuticals