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
BioWorld Today - Jun. 06, 2012
