Oxxon Therapeutics Reports Positive Preliminary Phase IIa Data with Chronic Hepatitis B Therapeutic Vaccine.

BOSTON -- PrimeBoost disease specific immunotherapy presented at the American Association for the Study of Liver Diseases Annual Meeting

Oxxon Therapeutics, Inc. announced today that data would be presented at the 56th Annual Meeting of The American Association for the Study of Liver Diseases (AASLD) on Monday November 14th in a plenary session. Oxxon will present positive interim data from a Phase IIa, 52-week study of its novel therapeutic vaccine comprising a PrimeBoost immunotherapeutic approach in patients with chronic hepatitis B. The study, which was conducted in two parts, found the therapy was safe and generally well tolerated. Overall, these data show that at 14 weeks, Oxxon's PrimeBoost immunotherapy alone elicited hepatitis B antigen loss in 9/40 (23%) of patients as compared to only 1/11 (9%) of those who received lamivudine alone. In addition, no patient receiving lamivudine had seroconverted by week 14 whereas 5/40 (13%) of patients having received immunotherapeutic alone had done so. This seroconversion rate was sustained to at least week 26 - longer-term follow up continues.

"Hepatitis B remains a major clinical challenge, with an urgent need for new approaches to clear the virus. Many patients do not respond to current treatments and antiviral resistance continues to be a challenge with long-term antiviral therapies," said Dr. Gill Pearce, Senior Director, Clinical Development at Oxxon Therapeutics and one of the study authors. "These results suggest that Oxxon's PrimeBoost immunotherapy offers the potential to be the first well tolerated immunotherapeutic treatment for this devastating disease and support the continued development of this product."

The hepatitis therapy under investigation uses Oxxon's heterologous PrimeBoost strategy aimed at generating an immunological response against hepatitis B-specific antigens. The therapy employs a DNA plasmid based vector containing hepatitis B antigens that is designed to prime the immune system. Subsequently, this initial response is then "boosted" using a Modified Vaccinia virus Ankara (MVA) based vector, which codes for the same hepatitis B specific antigens as the DNA prime.

Oxxon's presentation is scheduled for 5:45 on Monday, November 14th at the Moscone West Convention Center where AASLD is being held.

The Study Design and Interim Results:

This Phase IIa study was designed to evaluate safety, immunogenicity, and anti-viral efficacy of the immunotherapy in HBeAg+, antigen positive, chronic hepatitis B patients. Seventy-three HBeAg+ chronic hepatitis B patients were recruited for the entire study. The DNA and MVA viral vectors used express HBs and pre-S2 genes of the ayw strain of hepatitis B.

The study was conducted in two phases, initially to evaluate the optimal dosage, followed by the immunogenic and clinical activity. During the dose escalation phase, patients received two "priming" doses of DNA (either 2 x 1 mg or 2 x 2 mg) followed by two "boosting" doses of MVA (from 5 x 10(7) pfu to 5 x 10(8) pfu). In the first phase of the study, three dose regimens were assessed in 19 patients. All three dose regimens were found to be well tolerated and the highest dose regimen was therefore taken forward into the second phase.

During the efficacy phase, 54 patients were randomized to receive either immunotherapy alone, immunotherapy plus lamivudine, or lamivudine alone. Those randomized to receive immunotherapy (either with or without lamivudine) received two priming doses of DNA (2 x 2 mg) followed by two boosting doses of MVA (5 x 10(8) pfu). In both phases of the study, each immunization was given three weeks apart. Those randomized to receive lamivudine in combination with immunotherapy were given a four week run in treatment with lamivudine prior to any immunization followed by a further 10 weeks of lamivudine therapy (100mg/ day). Those randomized to receive lamivudine alone received 14 weeks treatment with lamivudine (100mg/ day).

Fourteen weeks after receiving the first immunization, high levels of HBeAg clearance and seroconversion were observed as shown below:

Oxxon
                            Oxxon         Immunotherapeutic Lamivudine
                       Immunotherapeutic   plus lamivudine     alone

                            (N=40)             (N=22)         (N=11)
--------------------- ------------------ ------------------ ----------
HBeAg loss                 9 (23%)            3 (14%)         1 (9%)
--------------------- ------------------ ------------------ ----------
Seroconversion             5 (13%)               0              0
--------------------- ------------------ ------------------ ----------

By week 26, HBeAg loss was reported in 29% of those that received immunotherapy alone and 14% had seroconverted, whereas in the lamivudine alone arm, none had lost HBeAg or serconverted at this timepoint. The difference in HBeAg loss between these two groups at week 26 was statistically significant (p = 0.049 by Chi-squared test).

The current study will continue to assess all patients out to 52 weeks, with final data expected first quarter 2006.

The trial was conducted at 11 outpatient study centers in Poland and Serbia & Montenegro. The principal investigators in the study were: W. Halota of Nicolaus Copernicus University, Bydgoszcz, Poland; D. Delic of Clinical Centre of Serbia, Belgrade, Serbia; D. Prokopowicz of Medical University of Bialystok, Poland; J. Kuydowicz of Bieganski Hospital, Lodz, Poland; J. Cianciara of Institute of Infectious and Parasitic Diseases, Warsaw, Poland; T. Mach of University Hospital, Krakow, Poland; R. Modrzewska of Medical University of Lublin, Poland; M. Fabri of Clinical Centre, Novi Sad, Serbia; D. Tomic of Clinical Centre of Serbia, Belgrade, Serbia; A. Horban of Warsaw Medical University, Warsaw, Poland; W. Kryczka of Principal Hospital, Kielce, Poland; and R. Anderson and G. Pearce of Oxxon Therapeutics.

About Oxxon Therapeutics:

Oxxon Therapeutics, Inc. (Oxxon) is advancing the next generation of innovative immunotherapeutics to treat patients with chronic infectious diseases and cancer. To date the Company has built a pipeline through its proprietary PrimeBoost platform, an approach that allows rapid development of products to selectively stimulate and enhance a potent cellular response. The Company has development programs in hepatitis, melanoma and HIV, two of which are in Phase II clinical trials. In addition, the Company is leveraging its enabling platform through partnerships with companies and academic collaborations.

For more information, please visit www.oxti.com