AVANIR Anthrax Antibody Effective at Neutralizing Key Anthrax Toxin in Live Animal Model

SAN DIEGO, Apr 30, 2003 /PRNewswire-FirstCall via COMTEX/ -- AVANIR Pharmaceuticals (Amex: AVN) presented in vivo animal data on its fully human antibody against the key toxin of the Class A biowarfare agent anthrax at a national symposium in Maryland today. The data showed that one molecule of the antibody, AVP-8C1, is capable of neutralizing more than two anthrax toxin molecules in rat models. This ratio shows exceptional potency and is the first example of an antibody's potency against a toxin at this very high or "sub-stoichiometric" level.

The presentation, "Anthrax Vaccination: A Source for a Panel of Potent Fully Human Monoclonal Antibodies using Xenerex(TM) Technology" was given at the 9th National Symposium -- Basic Aspects of Vaccines by Dr. Phillip Morrow, a co-inventor of AVANIR's Xenerex technology. Through the use of its Xenerex technology, AVANIR has discovered and developed a human monoclonal antibody that provides immediate post-exposure neutralization and immediate immunity in rats exposed to a lethal dose of recombinant anthrax toxins.

The antibody, AVP-8C1, binds to and neutralizes the protective antigen (PA). PA 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 the intracellular compartment and have a lethal effect. AVANIR's preclinical research to date demonstrates that a single dose of AVP-8C1 completely protects rats subsequently exposed to a lethal dose of recombinant anthrax toxins.

"The potency this antibody exhibits is extremely high," said Dr. Morrow. "We are very encouraged by this data, and plan to develop this antibody for use as a prophylactic and therapeutic drug to prevent and treat anthrax infections. Although speculative, AVP-8C1 may also play a role in the prevention and treatment of infections by antibiotic-resistant strains of anthrax."

"The data from this antibody demonstrates that our Xenerex technology, a proprietary technology developed by AVANIR, is well suited to generating human antibodies that may be useful for the treatment of important infectious diseases," said Gerald J. Yakatan, President and CEO of AVANIR Pharmaceuticals. "And because of the relative potency of antibodies such as AVP-8C1, significant advantages in the cost of producing the product are possible."

AVANIR Pharmaceuticals is developing AVP-8C1 for use as a prophylactic and therapeutic drug to prevent and treat anthrax infections. Grants from the U.S. Department of Defense administered through CCAT -- Center for Commercialization of Advanced Technology, have already been awarded to facilitate the Company's early antibody development efforts. AVANIR plans to work with Federal Authorities and the federal grant programs available under recently implemented biodefense initiatives to fund the required testing and eventual production of an antibody product. AVANIR is also in discussions with potential partner companies capable of antibody production in an effort to file an Investigational New Drug application seeking to begin clinical trials to evaluate the safety, tolerability, and pharmacology of AVP-8C1 in healthy human subjects.

There are three types of anthrax exposure: cutaneous, gastrointestinal and inhalational, of which the latter form is the most lethal. 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 annual boosters, to maintain its presumed protective effect. Antibiotics, the standard treatment of anthrax infection, are effective in killing anthrax bacteria, but have limited use once the anthrax toxins are released. The natural emergence or deliberate release of antibiotic-resistant strains of anthrax is an ongoing public concern.

In AVP-8C1, AVANIR Pharmaceuticals has exploited a third mechanism of defense against anthrax infections. In contrast to the anthrax vaccine, the protection afforded by a single dose of AVP-8C1 would be immediate. In contrast to antibiotics, AVP-8C1 acts against the key gateway component PA of the anthrax. By neutralizing this molecule the LF and EF toxins are denied entry into cells. AVP-8C1 can be envisaged in multiple scenarios, augmenting vaccination, as a stand alone prophylaxis, or synergistic in combination with antibiotics. The discovery and development of antibodies to the toxins of anthrax can meet significant unmet medical needs by providing protection from exposure to anthrax as well as extending the treatment window for those who are infected with anthrax.

The Development Process

AVP-8C1 is currently in preclinical development for use as a prophylactic and therapeutic drug to prevent and treat anthrax infections. Under the Bioterrorism Act of 2002, the FDA gave guidance on the evidence required to demonstrate the efficacy of new drug and biological products used to counter biological agents, when traditional efficacy studies in humans are not feasible. According to the guidelines, successful studies in relevant animal models will be considered sufficient to establish efficacy for licensure and marketing approval. AVP-8C1 is effective in preventing the lethal effects of anthrax toxins in the rat model. AVP-8C1 will be further evaluated in rabbits and nonhuman primates using Bacillus anthracis spore challenge. According to the guidelines, human clinical trials will be required to establish safety, tolerability, and pharmacology, but not efficacy.

About the Company

AVANIR Pharmaceuticals, based in San Diego, is a drug discovery and development company with a commercialized FDA-approved product (Abreva(R)) and products in clinical development for the treatment of pseudobulbar affect (Phase III), neuropathic pain (Phase II), and allergy and asthma (Phase I). AVANIR is engaged in small molecule research to develop treatments for central nervous system disorders and inflammatory diseases. Through the use of its 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.

SOURCE AVANIR Pharmaceuticals

Vince Heald, Media of Beck Ellman Heald, +1-858-453-9600, vheald@behmedia.com, for AVANIR Pharmaceuticals; or Patrice Saxon, Investor Relations of AVANIR Pharmaceuticals, +1-858-622-5202, psaxon@avanir.com