Updated CDX-110 Data in Glioblastoma Multiforme Presented at 44th Annual ASCO Annual Meeting

Business Wire, June 2, 2008

Survival and Time-to-Progression Reported From Open-Label Phase II Studies

CHICAGO -- AVANT Immunotherapeutics (Nasdaq: AVAN) and Pfizer, Inc. (NYSE: PFE) today announced the presentation of new data from two Phase 2 studies at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) for CDX-110, an investigational immunotherapeutic vaccine that targets the tumor-specific molecule epidermal growth factor receptor variant III (EGFRvIII). CDX-110 was generally well-tolerated with primary toxicity reported as local injection site reactions.

Included in the presentation were updated data from the Phase 2 ACTIVATE trial (n=21) and the continuation study, ACT II (n=23) of CDX-110 in patients with newly diagnosed EGFRvIII-positive glioblastoma multiforme (GBM).

* In the ACTIVATE study, median survival time was 26 months (95% CI: 21.6, infinity) and median time-to-progression (TTP) was 14.2 months. Median survival in a historical matched cohort was 15.2 months (17/17) (95% CI: 13.9, 20.5).(p=0.0001) with median time to progression of 7.13 months (p=0,0001). No significant adverse events were seen in this study.

* Preliminary results from the ACT II study currently estimate median overall survival to be 33.1 months, although the median has not yet been reached. The survival of a matched historical control group was 14.3 months (95% CI: 13.0, 16.2) and a subgroup treated with temozolomide (TMZ) of 15.2 months (95% CI: 13.9, 20.5 p=0.0078). Overall TTP was 16.6 months (95% CI: 10.8, infinity) compared with 6.4 months for the historical control group (95% CI: 5.0, 14.1). In this study, primary toxicity was reported as local injection site reactions.

"Vaccination with CDX-110 together with standard of care temozolomide in patients with glioblastoma multiforme increased time to progression and overall survival compared with a matched historical control group in these Phase 2 studies," said John Sampson, M.D., Associate Professor of Neurosurgery at Duke University Medical Center, who presented the data. "This is encouraging news for patients with this specific type of brain tumor, who are currently facing very limited treatment options. This treatment is being further studied in a randomized Phase 2b/3 trial to confirm these results."

Study design

The ACTIVATE trial studied CDX-110 vaccine in 21 patients with newly-diagnosed EGFRvIII-expressing GBM who had undergone surgical (gross-total) resection followed by conformal radiation therapy with concurrent oral temozolomide (75 mg/m2 per day) without tumor progression. CDX-110 mixed with granulocyte-macrophage colony stimulating factor (GM-CSF) (142 mcg) was administered intradermally. Sixteen patients received CDX-110 at two week intervals for three doses, while five patients received saline in a blinded fashion for the first three vaccinations. Thereafter, all patients received monthly CDX-110 injections mixed with GM-CSF until tumor progression. Safety was assessed through evaluation of adverse events, complete physical and neurological exams, and routine clinical laboratory studies. The ACT II study enrolled a total of 23 patients. The patient population and treatment scheme were similar to ACTIVATE, except that no early placebo was given and two dose schedules of maintenance temozolomide were studied (13 patients received 200 mg/m2 daily times five every 28 days, while 10 received 100 mg/m2 daily times 21 days every 28 days for a maximum of 12 cycles). Monthly CDX-110 vaccination mixed with GM-CSF was given on day 21 of each cycle until tumor progression. Safety was assessed in a similar fashion to ACTIVATE.

About EGFR vIII

EGFRvIII is a mutated form of epidermal growth factor receptor (EGFR) that is only expressed in cancer cells and not in normal tissue and is a transforming oncogene that can directly contribute to cancer cell growth, as it does in about 40 percent of GBM tumors.

AVANT is currently enrolling the Phase 2b portion of a Phase 2b/3 clinical trial called ACT III, which is evaluating CDX-110 in 90 patients at over 20 cancer centers across North America. The Phase 3 portion will not open until data is available from Phase 2b and pending further discussions with FDA.

About CDX-110

CDX-110 is an investigational immunotherapy that targets the tumor specific molecule EGFRvIII, a functional variant of the epidermal growth factor receptor (EGFR), which is a protein that has been well validated as a target for cancer therapy. This particular variant, EGFRvIII, was discovered in a collaborative effort between Bert Vogelstein, M.D. and Albert Wong, M.D. at Johns Hopkins University and Darell Bigner, M.D., at Duke University. Application of this discovery toward the development of the CDX-110 vaccine was further advanced by Dr. John Sampson, M.D. and his colleagues at the Duke University Brain Tumor Center in collaboration with Amy Heimberger, M.D. at the M.D. Anderson Cancer Center. Unlike EGFR, EGFRvIII is not present in normal tissues, suggesting this target will enable the development of a tumor-specific therapy for cancer patients. Furthermore, EGFRvIII is a transforming oncogene that can directly contribute to cancer cell growth. While originally discovered in GBM, the most common and aggressive form of brain cancer, the expression of EGFRvIII has also been observed in various tumors such as breast, ovarian, metastatic prostate, colorectal, and head & neck cancers. Celldex owns the rights to EGFRvIII vaccines and is pursuing the development of CDX-110 for GBM therapy, as well as in other cancers through additional clinical studies.