It's really quite simple, local and very targeted.
"We inject the surface tumor with a therapeutic agent and then administer electric pulses through a generator that create temporary pores in the membrane of cells in the selected tissue, dramatically increasing the uptake of the agent for its cancer-killing benefits," Punit Dhillon, CEO of OncoSec Medical (OTC:ONCS), says in an interview with BioTuesdays.com.
"We've seen an over 4,000-fold increase in the uptake of the agent, and when the electric pulses are stopped, the pores close, and the agent is trapped in the cell allowing it to perform its intended functions."
As a result of this targeted approach, he says the amount of drug needed to induce cell death is substantially lower than the dose required in traditional chemotherapy. And the reduced amount of a locally delivered drug diminishes or eliminates the harmful side effects commonly associated with traditional chemotherapy, which is delivered systemically.
"While the concept is simple on the surface, there's a lot going on at the cellular level," he adds.
Known as electroporation, the OncoSec Medical System (OMS) platform has two approaches: OMS ElectroImmunotherapy and OMS ElectroChemotherapy. While using different anti-cancer drugs, both techniques have shown selective destruction of cancerous cells and tumors in early-and late-stage trials, while sparing healthy normal tissue in the treated areas.
Mr. Dhillon contends the technology is designed to "address the drawbacks of conventional therapies by being tissue sparing; providing potential functional, cosmetic and quality of life benefits; being less invasive and reducing side effects; and potentially reducing both treatment and post-treatment costs."
Electroporation Enhances Therapeutic Potency
The "ElectroOncology" concept traces its roots to Inovio Pharmaceuticals where Mr. Dhillon led an employee spin-out of the technology, existing clinical data and IP to create OncoSec in March 2011.
According to Mr. Dhillon, Inovio had invested a significant amount of funds and effort in the development of the technology before it was acquired by OncoSec. "And we have been able to leverage this experience by quickly progressing into Phase 2 clinical trials for our electroimmunotherapy program as well as partnering discussions for our electrochemotherapy program."
OMS ElectroChemotherapy is a targeted ablation therapy, which utilizes the OMS to locally deliver bleomycin, an approved anti-cancer drug, to the tumor. The therapy preferentially kills targeted cancer cells while sparing surrounding normal healthy tissue.
OMS ElectroChemotherapy had been tested in over 400 patients in 13 countries and at more than 50 clinical sites before Inovio discontinued the program in a corporate restructuring. "Through the asset acquisition, we accumulated a significant database of clinical data in a variety of tumor types," Mr. Dhillon says.
The therapy has been developed up to Phase 3 clinical trials in the U.S. for the treatment of recurrent head and neck cancer and in Phase 1/2 for the treatment of recurrent breast cancer. In addition, Phase IV pre-marketing studies to support the commercialization of OMS in Europe were also performed for the treatment of primary and recurrent head and neck cancers and cutaneous skin cancers.
Mr. Dhillon says that in previous clinical studies with melanoma and non-melanoma skin cancer patients, OMS ElectroChemotherapy achieved objective response rates of 99% and complete response rates of 89%.
"Given that there are over two million new cases of non-melanoma skin cancers diagnosed each year in the U.S., the therapy provides an effective and cost efficient alternative to surgery, without the removal of healthy tissue, which minimizes disfigurement and functional loss," he contends.
Moreover, the incidence of non-melanoma skin cancer is rapidly rising in young adults because of increased sun exposure.
Since acquiring the assets a year ago, the company has been working to compile and analyze data from the Phase III and IV studies carried out in the U.S. and Europe.
Treatment of Head and Neck Cancer
The Phase IV head and neck cancer results, carried out in Europe, will be presented at a medical conference in Poland to take place April 18 to 21. An interim analysis of two randomized Phase III trials, comparing OMS ElectroChemotherapy with surgery in recurrent head and neck cancer, will be presented at a medical conference in Toronto to take place July 21 to 25.
"With this data, we expect to finalize our clinical development plan and move forward with commercializing the OMS ElectroChemotherapy platform with a partner, either regionally or globally," Mr. Dhillon says. He figures the therapy has a conservative market potential of more than $1 billion a year to treat various solid tumors and hopes to announce a partnership later this year.
OncoSec's corporate focus is skin cancer, but the technology can be applied to other solid tumors of the head and neck, breast, liver and pancreas. One in five Americans will develop skin cancer in his or her lifetime. In the case of melanoma, there were an estimated 123,000 new cases in 2011, resulting in some 10,000 deaths.
OMS ElectroImmunotherapy uses electroporation and a DNA cytokine called interleukin-12 (DNA IL-12), which is known to prompt the body's innate and adaptive immune systems to seek out and kill cancer cells.
In an earlier Phase I melanoma study with 24 patients in the U.S., the therapy was shown to be safe and effective. Some 53% of patients demonstrated a partial response rate, with 100% clearance of distant, untreated tumors in 16% of patients.
U.S. Phase I Melanoma Trial; Patient A - Complete Response
The study also determined there were no increased levels of IL-12 or interferon-gamma in blood serum, "which is important in showing that the therapy has no toxicity issues," Mr. Dhillon says.
"Results from our Phase 1 study demonstrated that DNA IL-12 and electroporation has the potential to establish a new standard of care for the treatment of late-stage metastatic melanoma," he adds.
Last month, OncoSec began dosing patients in two Phase 2 trials of late-stage metastatic melanoma and Merkel cell carcinoma. A third Phase IIclinical trial in cutaneous T-cell lymphoma is scheduled to start in April. A total of 67 patients will be enrolled in the three studies.
CTCL and MCC are rare forms of skin cancer. CTCL is very aggressive and late-stage disease can be lethal, while MCC is three times more deadly than melanoma.
OncoSec expects to release interim data from the three trials in the fourth quarter of this year. If the final data, which are due in 2013, are successful, the company plans to file an Investigational New Drug Application with the FDA in 2013 to begin a pivotal trial in one or more of the skin cancer indications.
Mr. Dhillon says DNA IL-12 and electroporation are comparable to or exceed response rates of other approaches to melanoma, including Bristol-Myers' Yervoy and Genentech's Zelboraf, which were both approved last year.
He says Yervoy has not shown much improvement in response rates, compared with earlier treatments using interferon and Dacarbazine. While it has increased survival by eight to ten months, it also exhibits severe side effects. Response rates for Zelboraf exceed Yervoy, he notes, but the drug is limited to a certain patient population. Patients also can develop resistance to the drug, and when they discontinue treatment, melanoma reoccurs.
"With DNA IL-12, we have not seen any signs of drug resistance, and with a low dose, we hope to demonstrate a better safety profile than other products currently available," Mr. Dhillon says. "Our less invasive treatments are designed to give patients with life-threatening cancers the ability to have a higher quality of life."