Tanox, Inc. Reports Positive Results From Phase 2 Clinical Trial Of TNX-355, An Entry Inhibitor To Treat HIV

HOUSTON, Oct. 26 /PRNewswire-FirstCall/ -- Tanox, Inc. today reported positive Phase 2 clinical results of its novel HIV drug candidate, TNX-355. The 24-week results of the study show that TNX-355 at the 10 mg/kg dose, when given in combination with optimized background therapy (OBT), produced a considerably greater reduction in viral load in HIV-infected patients than did placebo in combination with OBT. TNX-355 was well tolerated, with no serious adverse events related to the drug. The study met its primary endpoint with TNX-355 plus OBT demonstrating a statistically significant reduction in viral load -- the level of HIV in the bloodstream -- compared to placebo plus OBT at Week 24.

Treatment with the 10 mg/kg dose of TNX-355 resulted in a viral-load reduction of 1.16 log10, compared with a 0.20 log10 reduction in the placebo group, representing a 0.96 log10 greater reduction (p<0.001) in viral load in the last observation carried forward analysis.

The reduction was maintained even with the more conservative method of analysis in which patients without a Week 24 value had their baseline value assigned instead of carrying the last observation forward. In this analysis, treatment with the 10 mg/kg dose of TNX-355 resulted in a viral-load reduction of 1.19 log10, compared with a 0.32 log10 reduction in the placebo group, representing a 0.87 log10 greater reduction (p=0.002) in viral load.

The mean maximum viral-load reduction from baseline during the 24-week period in the 10 mg/kg dose arm was 1.97 log10 (p=0.002).

"This trial demonstrates the antiviral activity of TNX-355 in highly treatment-experienced patients, who often have few therapeutic options," said Dr. Jeffrey Nadler, professor of Medicine and director of Clinical Research, Division of Infectious and Tropical Diseases at the University of South Florida in Tampa and an investigator in the Phase 2 clinical trial of TNX-355. "The study results support the strategy of blocking HIV entry. Perhaps most encouraging, because of TNX-355's novel mechanism of action, we may have a powerful new weapon against multi-drug resistant HIV."

Treatment with the 15 mg/kg dose of TNX-355 resulted in a viral-load reduction of 0.95 log10, compared with a 0.20 log10 reduction in the placebo group (p=0.003), representing a 0.75 log10 greater reduction in viral load in the last observation carried forward analysis.

The Phase 2 clinical trial was designed to compare the effects of two doses of TNX-355 -- 10 mg/kg and 15 mg/kg -- to that of a placebo. All study patients received OBT (a standard-of-care regimen). Patients were randomized 1:1:1 to receive 10 mg/kg, 15 mg/kg or placebo every two weeks. Patients in the 10 mg/kg dose received a loading dose of 10 mg/kg every week for eight weeks. The primary endpoint was the mean change from baseline in HIV RNA at Week 24.

Secondary Endpoints

Key secondary endpoints included: the proportion of subjects achieving a viral-load reduction of at least 0.5 log10; the proportion of subjects achieving a viral-load reduction of at least 1.0 log10; and the mean change in CD4+ cell count from baseline.

In the 10 mg/kg dose arm, 56 percent of patients achieved a viral-load decrease of at least 0.5 log10 at Week 24, demonstrating the durability of the reduction. In addition, 44 percent of patients had a viral-load decrease of at least 1.0 log10 at Week 24.

"These data reveal that TNX-355 provides significant virologic benefit," said Nancy Chang, Ph.D., president and CEO of Tanox. "TNX-355 has the potential to provide considerable advantages over the current standard-of-care for HIV patients, and we look forward to working with the FDA on next steps toward bringing this therapy to a growing number of patients who have limited treatment alternatives."

A mean CD4+ cell count increase was observed in all arms of the study, but was not significantly different between the treatment groups and placebo. Both doses of TNX-355 were safe and well tolerated, with no severe adverse events or laboratory abnormalities related to the drug. No infusion-site reactions were reported.

TNX-355, Viral Entry Inhibitors, and Trial Overview

TNX-355 is a humanized monoclonal antibody and part of an emerging class of HIV therapies known as viral-entry inhibitors. These compounds prevent HIV from breaching immune system cells by inhibiting the virus' ability to utilize key receptors necessary for entry. Entry inhibition is a promising new strategy for HIV therapy. Entry can be blocked by several unique mechanisms. Some agents target viral proteins; however, the virus readily mutates to develop resistance. Other entry inhibitors target certain co-receptors such as CCR5 or CXCR4. The virus may thwart the co-receptor inhibition strategy by adapting the ability to use either or both co-receptors to gain entry into target cells.

TNX-355, which is administered intravenously, is distinct from other entry inhibitors in that it "coats" the CD4+ cell receptors, the primary target of HIV infection. Since TNX-355 blocks HIV entry at a step prior to the co- receptor interaction, the drug candidate is "co-receptor tropism independent," with the ability to block both CCR5 and CXCR4 virus -- a major advantage. The blockade presented by TNX-355 also does not depend on targeting mutation-prone viral proteins.

All 82 patients in the TNX-355 Phase 2 clinical trial were tripled-class treatment-experienced HIV-1-positive patients who had viral loads of greater than or equal to 10,000 copies/mL, with CD4+ cell counts of at least 50 cells/mL, and were failing or had recently failed highly active antiretroviral therapy (HAART) at the time of study entry.

Continued Development

The Phase 2 trial is ongoing with a planned continuation to 48 weeks. Additional data from the trial was submitted in an abstract to the 45th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), scheduled for Dec. 16-19, 2005 in Washington, D.C.

Following an end-of-Phase 2 meeting with the FDA, Tanox's intention is to move forward with a planned Phase 3 study of the drug in 2006 and evaluate partnership opportunities.

"TNX-355 has the potential to empower clinicians and patients with a new tool to fight increasingly drug-resistant strains of HIV, and help patients better control the virus," said Dr. Stanley Lewis, Tanox medical director for TNX-355. "Add to that the minimal side effects, and we believe TNX-355 could benefit not only treatment-experienced patients, but potentially patients unable to tolerate their current therapies, those suffering from treatment- limiting co-morbidities or who harbor drug-resistant virus."

Investor Conference Call

Tanox will host a conference call for investors today at 10 a.m., EDT. To participate in the conference call, U.S. callers should dial 866-277-1182. International access is available by calling 617-597-5359. The call pass code is 12005931. Live audio of the call will be webcast on the Internet. The webcast can be accessed from the Tanox Web site at http://www.tanox.com in the Investor Relations section. An audio replay of the webcast will be available beginning at 11 a.m., EDT, Oct. 26 through 11 a.m., EDT, Nov. 2, 2005. Access phone numbers for the replay are: 888-286-8010 (U.S.) and 617-801-6888 (international); conference pass code 84512229.

About HIV/AIDS

Since first reported in the United States in 1981, HIV has become a pandemic. A member of the Retroviridae family, the Human Immunodeficiency Virus (HIV) harms the body's immune system by attacking the cells that defend the body against illness, and can lead to AIDS as viral infection grows. More than 40 million people worldwide are currently living with HIV or AIDS, and 95 percent of the infected population lives in the developing world. Sales of HIV medications worldwide totaled more than $5.7 billion in 2003, including $3.8 billion in U.S. sales.

About Tanox, Inc.

Tanox is a biotechnology company specializing in the discovery and development of biotherapeutics based on monoclonal antibody technology. The company develops innovative therapeutic agents for the treatment of immune- mediated diseases, inflammation, infectious disease and cancer. Tanox's first-approved drug, Xolair(R) (omalizumab), is the first anti-immunoglobulin E (anti-IgE) antibody to be brought to market. Xolair was developed in collaboration with Genentech, Inc. and Novartis Pharma AG and was approved for marketing in the United States for adult and adolescent patients with moderate-to-severe, confirmed allergic asthma. Tanox is based in Houston, Texas and maintains a manufacturing facility in San Diego, California. Additional corporate information is available at http://www.tanox.com .

This news release contains forward-looking statements regarding the potential for TNX-355 as a treatment for HIV-1-infected patients. These statements are based on Tanox's current beliefs and expectations, and are subject to risks and uncertainties that could cause actual results to differ materially. The absence of safety concerns after 24 weeks of treatment in 82 patients does not ensure that safety issues will not be identified after extended treatment or in larger-scale clinical trials. The therapeutic potential of TNX-355 as a treatment for HIV-1-infected patients is subject to the risks inherent in drug development. Success in early stage clinical trials does not ensure that later-stage or larger-scale clinical trials will be successful, and the results achieved in later stage trials may not be sufficient to meet applicable regulatory standards. Problems or delays may arise during clinical trials or in the course of developing, testing or manufacturing drugs. For more detailed information on the risks and uncertainties associated with Tanox's drug development and other activities, see Tanox's periodic reports filed with the Securities and Exchange Commission.

Photo: NewsCom: http://www.newscom.com/cgi-bin/prnh/20050207/TNOXLOGOPRN Photo Desk photodesk@prnewswire.comTanox, Inc.

CONTACT: Steve Sievert of Tanox, Inc., +1-713-578-4211, orssievert@tanox.com

Web site: http://www.tanox.com/