NewCo News: Advaxis Uses Listeria Bug to Launch Attack on Cancer Cells

Advaxis Inc. reported positive preliminary results from a Phase II trial of its human papillomavirus (HPV) immunotherapy product, ADXS-HPV, at the American Society of Clinical Oncology meeting in Chicago this week.

In the ongoing trial at 22 sites in India, 109 patients with late-stage disease received ADXS-HPV with and without cisplatin. Survival at nine months was 31 percent, with four complete responses and seven partial responses.

Fifty-six percent of patients achieved disease control, defined as complete response, partial response or stable disease. Thirty-six percent experienced a Grade 1-2 adverse event, but only 0.9 percent suffered a Grade 3 serious adverse event.

A safer and less toxic form of cancer treatment is the goal behind the Princeton, N.J.-based company's development program.

Patients with cancer have come to expect that cancer treatment will be harsh and dangerous due to the necessity of using potent drugs to stop the out-of-control growth of the cancer cells. Advaxis is working on a new type of immunotherapy based on a common food poisoning bug.

Advaxis, founded in 2002, is engineering the common foodborne pathogen, Listeriamonocytogenes, to carry a modified antigen payload designed to train the immune system to seek and destroy cancer cells with the same vigor that it attacks its familiar enemy, Listeria.

Listeriosis is a foodborne illness that can be serious, resulting in several hundred deaths in the U.S. each year. The pathogen is present and common in the food supply. It is most dangerous to people with compromised immune systems, such as pregnant women or HIV patients. That is due to an elaborate immune response "hardwired" into the genome, according to Advaxis.

"We take advantage of that very well-developed and elaborate immune response by bioengineering the Listeria," Advaxis CEO Tom Moore told BioWorld Today.

Two important changes are made to the Listeria bug to transform it into a cancer therapy. First, it is attenuated to make it safe to inject into the body. Second, it is engineered to secrete a fusion protein consisting of listeriolysin (Lm-LLO) and a target antigen of interest. Lm-LLO stimulates a powerful immune response that is then redirected to the target antigen.

"Before, we've come in with a variety of poisons or radiation to try to kill the cancer, hopefully just before we kill the patient," Moore said. "Immunotherapy works to turn on the body's own immune system to attack cancer."

Cancer immunotherapy is becoming one of the hottest trends in biotech. Provenge (sipuleucel-T, Dendreon Inc.) for prostate cancer and Yervoy (ipilimumab, Bristol-Meyers Squibb Co.) for melanoma, have become early successes in the field, showing that biotherapeutics can train the immune system to seek and destroy tumor cells.

Advaxis is developing three Listeria-based cancer therapies: ADXS-HPV for cervical and other cancers; ADXS-PSA for prostate cancer; and ADXS-HER2 for HER2-overexpressing cancers and canine osteosarcoma.

ADXS-HPV is Advaxis's most advanced product. It successfully completed a Phase I trial and is being evaluated in several Phase II trials. Two of those focus on patients with metastasized, progressive cervical cancer that has not responded to previous treatment. One is being carried out in India, one in the U.S. Another trial focuses on locally advanced cervical cancer.
 

A fourth, UK-based Phase I/II trial will evaluate ADXS-HPV in patients with head and neck cancer with endpoints of safety, dose escalation and immunology.

Historically, the expected survival for that cohort â?? those previously treated with radiation and/or chemotherapy, with subsequent relapse â?? is only 5 percent, according to Advaxis. It is hoping to exceed that number by a wide margin in the ongoing trial.

The U.S.-based Phase II trial of ADXS-HPV will evaluate safety and efficacy in patients with cervical intraepithelial neoplasia Grades 2 and 3 (CIN 2/3) by CIN remission using loop electrosurgical excision procedure.

Advaxis completed the first three dose cohorts in that trial, finding that 52 percent of CIN2/3 lesions regressed to CIN 1 or normal in the treatment arm, with no serious adverse events. "We've totally eliminated all of the cervical cancer in three patients," Moore said, pointing out that unlike typical cancer therapies, Advaxis' immunotherapies have potential to work better over time, as they retrain the immune system. "The immune system is often damaged because of previous exposure to cancer treatment."

Because the Listeria system is a platform technology, it can be used to create a virtually unlimited number and variety of drugs. Advaxis has a large number of potential candidates, and once it demonstrates that the basic platform is effective, the company will take those drugs through the proof-of-concept phase and license them out.

The company recently announced a research collaboration with the Karolinska Institutet in Stockholm, Sweden, to develop immunotherapies for allergic diseases.

Over the past three and a half years, Advaxis has raised about $29 million in the form of equity offerings, convertible debt and other financing instruments, through 11 different raises. "The technology is pretty compelling," Moore said.



 BioWorld Today - Jun. 06, 2012