Advaxis Evaluates Higher Dose and Repeat Cycles of ADXS-HPV in Phase 1/2 Cervical Cancer Trial

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PRINCETON, N.J., June 16, 2014 (GLOBE NEWSWIRE) -- Advaxis, Inc. (Nasdaq:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, announced that the Georgia Regents University (GRU) Cancer Center has received Institutional Review Board (IRB) approval to initiate a Phase 1/2 trial evaluating higher doses and repeat cycles of ADXS-HPV in patients with recurrent cervical cancer. The trial will be conducted at GRU under the direction of Dr. Samir Khleif, Director, GRU Cancer Center. ADXS-HPV is Advaxis's lead Lm-LLO cancer immunotherapy product candidate, designed to target HPV-associated cancers.

This Phase 1/2 study is designed to evaluate the safety, efficacy and immunological effect of the highest-tolerated dose of ADXS-HPV administered in repeat cycles of treatment to patients with cervical cancer whose disease recurred after receiving one prior cytotoxic treatment regimen. Advaxis's earlier Phase 2 clinical study in 110 women with recurrent cervical cancer had already demonstrated that a single cycle (3 doses) of ADXS-HPV at a dose of 1x109 colony forming units (CFU) is well-tolerated with complete and partial tumor responses as well as an apparent survival benefit. Building on this data, among the purposes of this study is to evaluate the effect of repeat cycles of treatment (multiple doses) of ADXS-HPV at higher doses.

Higher doses, equivalent to 1x1010 CFU, along with multiple cycles of treatment have been administered to pet dogs with naturally occurring canine osteosarcoma and preliminary results from the on-going clinical trial show statistically significant overall survival with only minor side effects. In addition, laboratory experiments clearly show improved activity against cancer when ADXS-HPV is given at higher doses and in repeat cycles of treatment. Advaxis believes that repeat cycles of treatment at higher doses may further improve the positive clinical benefits already observed in its prior Phase 2 study.

Dr. Robert Petit, Chief Scientific Officer of Advaxis, commented, "We have already seen safety and efficacy data from a single cycle of ADXS-HPV at the low dose of 1x109 CFU. We hope to improve on the clinical outcomes seen in our Phase 2 trial by using a higher dose and repeat cycles of treatment. This high-dose Phase 1/2 clinical study will run in parallel with our planned pivotal Phase 3 registration program for ADXS-HPV in patients with cervical cancer."

Dr. Petit further stated, "The 100-1000 fold greater attenuation of the Advaxis vector coupled with the higher secretion of the tumor antigen per CFU, should pair together to significantly amplify signaling of the immune system and result in a greater number of cancer fighting Tcells. Recurrent cervical cancer is a fatal disease and is resistant to treatment. These women deserve the strongest treatment effect we can generate, in an attempt to prolong their survival."

The final results from Advaxis's prior Phase 2 study were recently reported at the 2014 American Society of Clinical Oncology Annual Meeting, and showed that 22% (24/109) of the patients were long-term survivors (>18 months). 18% (16/91) of patients were alive for more than 24 months. In this Phase 2 study, 32% (35/109) of patient were alive at 12-months and a tumor response rate was observed in 11% (including complete responses and partial responses) of patients with a median duration of response of 9.5 months. A disease control rate (>three months) was observed in 38% (42/109) of patients. These results were achieved with the lowest dose of ADXS-HPV that was tested in Phase 1, and at this dose 68% of the patients did not report any ADXS-HPV related effects. The remainder patients experienced only low grade (1-2) transient effects the day of dosing. 1 patient had a grade 3 fever that responded to treatment with acetaminophen (Tylenol).

About the Phase 1/2 High-Dose Trial

This Phase 1/2 study will advance in two phases, starting with the highest ADXS-HPV dose and reducing the dose only if dose limited toxicities(DLT) occur in a specified number of patients. All patients will be divided into cohorts of three each. The phase 1 portion of the study will enroll 3 to 12 patients based on observed adverse events and/or observation of DLT within the dose cohorts. The phase 2 portion of the study will enroll 31 patients to have sufficient power to detect a 1.5-month increase in progression free survival (PFS). In addition to PFS and tumor response, the study will measure immunological effects in the blood, specifically on peripheral blood mononuclear cells (PBMCs) and serum for the presence of specific activated Tcells and for cytokines, chemokines and other potential markers. Exploratory studies will be to assess biomarkers, gene expression, and the potentially the immunologic tumor microenvironment for infiltration of cancer fighting Tcells and the reduction of tumor protecting Tregs and MDSCs.

About Dr. Samir N. Khleif

Dr. Khleif is Director of the GRU Cancer Center and former Chief of the National Cancer Institute's (NCI) Cancer Vaccine Section, medical oncology consultant with the National Naval Medical Center, and Professor of Medicine at the Uniformed Services University of the Health Sciences. His research group designed some of the first cancer vaccine clinical trials targeting specific genetic changes in cancer cells, studying ways to enlist the immune system's cooperation with cancer treatment, both by bolstering its ability to attack cancer cells and inhibiting its faulty interference with cancer treatment. During his tenure at the NCI, Dr. Khleif served as the Director General and Chief Executive Officer of the King Hussein Cancer Center and then of the King Hussein Institute for Biotechnology and Cancer, appointed by the Secretary of the Department of Health and Human Services through an agreement between the United States Government and the Kingdom of Jordan. He has also served as a Special Assistant to the FDA Commissioner, leading oncology efforts to make drug discovery and development more efficient, innovative, and cost effective.

About GRU Cancer Center

The GRU Cancer Center in Augusta, Ga., provides cancer care as a cooperative organization for Georgia Regents University. The Cancer Center's patients-first model is built on a foundation of teamwork and synergy between the research and clinical facilities. The GRU Cancer Center, which is working toward NCI designation, includes a 167,000-square-foot research building, opened in 2006, and a clinical facility that opened in 2010. Together, they provide state-of-the-art research and treatment, including several first-in-human protocols. The major investments the university and its health system have made in cancer in recent years make it fertile ground to produce the next big advancement in cancer research and clinical care.

About Advaxis, Inc.

Advaxis is a clinical-stage biotechnology company developing multiple cancer immunotherapies based on its proprietary platform intended to redirect the immune system to kill cancer. The Advaxis technology, using bioengineered live attenuated bacteria, is the only known cancer immunotherapy shown in preclinical studies to neutralize Tregs and MSDCs, that protect the tumor microenvironment from immunologic attack and contribute to tumor growth. Advaxis's lead immunotherapy, ADXS-HPV, targets human papillomavirus (HPV)-associated cancers and is in clinical trials for three indications: Phase 2 in invasive cervical cancer, Phase 1/2 in head and neck cancer, and Phase 1/2 in anal cancer. The FDA has granted Advaxis orphan drug status for each of these three indications. The Company plans to initiate a registrational clinical program for cervical cancer in 2014 and has established licensing partners in India and Asia for commercialization in those regions.

Advaxis's second immunotherapy candidate in clinical testing will be ADXS-PSA, which is being developed to address prostate cancer. Advaxis is planning to file an IND with the FDA and initiate a Phase 1 clinical study with ADXS-PSA in 2014. Advaxis is also developing ADXS-cHER2, to target the HER2 receptor, which is overexpressed in certain solid-tumor cancers, including pediatric bone cancer (or osteosarcoma), breast cancer, and gastric cancer. Advaxis is developing ADXS-cHER2 for both human and animal-health, and has seen promising results in canine osteosarcoma, which is considered a model for human bone cancer. Advaxis is pursuing a clinical program in pediatric osteosarcoma and has licensed ADXS-cHER2 and three other immunotherapy constructs to a major animal-health company. Advaxis is planning to file an IND for ADXS-cHER2 in HER2 overexpressing cancers.

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Forward-Looking Statements

This news release contains forward-looking statements, including, but not limited to: statements regarding Advaxis's ability to develop the next generation of cancer immunotherapies; the safety and efficacy of Advaxis's proprietary immunotherapy, ADXS-HPV; whether higher doses and multiple treatment cycles of ADXS-HPV can further improve clinical outcomes and quality of life; Advaxis moving forward with a registration program in recurrent cervical cancer; the collaborative efforts of Advaxis's licensing partners; the initiation or a registration clinical trial program for cervical cancer in 2014; Advaxis's development of ADXS-cHER2 for both human and animal health and its pursuit of a clinical program in pediatric osteosarcoma. These forward-looking statements are subject to a number of risks, including the risk factors set forth from time to time in Advaxis's SEC filings, including but not limited to its report on Form 10-K for the fiscal year ended October 31, 2013, which is available at Advaxis undertakes no obligation to publicly release the result of any revision to these forward-looking statements, which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events, except as required by law. You are cautioned not to place undue reliance on any forward-looking statements.

CONTACT: Advaxis Contact: Lisa Caperelli Senior Director of Investor Relations and Corporate Communications Advaxis, Inc. 215.206.1822 Media Contact: Tiberend Strategic Advisors, Inc. Amy S. Wheeler 646.362.5750