[Editor's note: The author has made some changes to the end of the article and the conclusion since original publication.]
The problem with cancer treatment that makes it truly a scourge is differentiating cancer cells from healthy cells. The immune system can't do it and doesn't attack tumors as it does any other pathogenic disease. Standard cancer treatments can't do it, as chemotherapy that is designed to stop cell division and shrink tumors also stops division of healthy cells, making people very sick. Radiation certainly doesn't do it, as radiation indiscriminately kills healthy cells along with cancer cells.
But advances have been made, and they largely have to do with "tagging" cancer cells in some way -- usually by having them absorb something external, something the body or administered medications can recognize, lock on to, and destroy. There are basically three ways to do this. One is to prime the immune system with tumor antigen in vitro and re-administer, hoping immune cells have picked up cancer markers and will now attack in vivo. Another is to reprogram a virus to infiltrate cancer cells and either attack them or mark them with new genetic material so they can be attacked. The third, which I would like to focus on here, is to open cancer cell membranes via a process called electroporation, or creating pores through administering electric current. Direct electric current creates these pores in the cell membrane, and from there the cells can be destroyed directly or else markers can be taken up by the cancer cells, which are then targeted for destruction.
Electroporation as a method of cancer treatment is being pursued all over the globe by universities, private institutions, and biotech companies alike. A combing of active electroporation clinical trials on clinicaltrials.gov yields a list of 10 initiatives in several different countries. The criteria for "active clinical trial" applied here is that the trial is either about to recruit, actively recruiting, or post-recruitment and gathering data, and has been updated by the sponsors within the last 12 months. All other trials are not included here.
Of these 10, four are sponsored by small university or private medical institutions, which rarely go beyond Phase II without being picked up by a corporation, as Phase III costs are too expensive for non-corporate entities to shoulder. Six are sponsored or co-sponsored by small to midsize biotech companies, including Bioalliance Pharma, a company on the French exchange; OncoSec (OTCQB:ONCS); Scancell (a London company); Inovio (INO); and Angiodynamics (ANGO). First I will give a rundown of these trials by sponsor, and follow up each with an investment analysis where appropriate.
Non-Corporate Electroporation Trials
The four non corporate-sponsored cancer electroporation trials currently active are sponsored by Sloan Kettering in Manhattan, Mary Crowley Medical Research Center in Dallas, VU University in the Netherlands, and the Clinical Research Office of the Endourological Society (CROES) also in the Netherlands. Three of the four are Phase I trials, the last Phase II. Any are equally likely to be picked up by a corporate sponsor if and when Phase II results show promise, so though they are not investable yet, success means they eventually will be. Also, success will have implications for and affect tradable companies pursuing a similar course to cancer treatment.
The first Phase I to be completed will be VU University's, estimated for July 2013. Currently recruiting with a quota of 10, this one is indirectly related to Angiodynamics as VU will be using ANGO's Nanoknife technology -- FDA approved for the general ablation of soft tissue by electroporation, but not specifically as a cancer treatment. VU will be using Nanoknife to ablate malignant liver tumors. Success in this trial will be good news for ANGO investors. This use of electroporation is more direct than using it to tag cancer cells, in that the electroporation is strong and continuous until apoptosis, or programmed cell death. If a cell membrane remains open for long enough, the cell commits suicide. The advantage of electroporation in this instance is that only the cells that are given a DC current die, as opposed to radiation-treated tumors or tumors that are heated or frozen in which cases the radiation, heating, or freezing can easily affect healthy cells, especially in sensitive places like the liver.
On the heels of VU University is Sloan Kettering with an electroporation Phase I melanoma trial estimated for completion in October 2013, recruiting with an enrollment target of nine. The goal of this trial is to get immune system dendritic cells to express melanoma antigens and then attack melanoma after being injected subcutaneously. The way Sloan Kettering is doing this is to have the dendritic cells take up the antigen genes in vitro via electroporation, and then re-inject the mix back into the patient, and test for a systemic immune response.
Third is Mary Crowley, with a large Phase I trial with an enrollment target of 50 patients estimated to be complete in December 2016, though it will probably be converted into a Phase II trial at some point considering its size. This one is targeting solid tumors by electroporation to take up a combination of immune enhancing factors that, separately, have shown ability to enhance immune response but have never been tested together. Bringing up the rear is CROES, testing ANGO's Nanoknife in a large 200-patient Phase II trial for ablation of prostate cancer by electroporation. Data will be collected for three years after the last treatment, and completion is only estimated for 2019. Phase IIs have been transformed directly into Phase IIIs in the past, so if interim data starts coming in positive, the trial may be expanded to Phase III numbers and ANGO could reap the benefits of Nanoknife success sooner than one would think.
This leaves six active trials remaining. The closest to completion is OncoSec's Phase II for merkel cell carcinoma, scheduled for December 2013 according to clinicaltrials.gov. As the company closest to completing a Phase II trial, OncoSec is way ahead of the pack and December will be a big month for ONCS shareholders. OncoSec's approach is to electroporate cutaneous tumors with genes that produce an immune system protein called interleukin 12 (IL-12). The genes infiltrate the electorporated cancer cells, which then start producing the IL-12 and the immune system targets and attacks. In a previous Phase I trial on melanoma, interim results on 13 patients showed a complete response in five out of 13 patients, and six more with a partial response for a very impressive 11/13 or 85% overall response to treatment, and 39% complete response rate. OncoSec is also conducting a phase II for cutaneous lymphoma using the same treatment scheduled for completion in 2015.
OncoSec has zero debt on its balance sheet and an accumulated deficit of less than $10 million in over two years of operation. With a market cap of only $33 million, that puts ONCS in the very risky illiquid micro-cap region. But positive Phase II results along the lines of the Phase I could easily change that, depending on who's paying attention.
Bioalliance in France will be next in line with results coming in around March 2014. This Phase I/II is fairly straightforward in that it is testing the effect of a drug called plasmid encoding antiangiogenic metargidin peptide (plasmid AMEP), which inhibits cancer cell growth like a targeted form of chemotherapy. It will be administered in this 36 patient trial via intramuscular electroporation. This is not designed to induce a systemic immune response against cancer, but rather to kill locally.
March 2014 will be a big month for two more companies, Angiodynamics and Inovio. ANGO has the advantage of "subcontracting" its clinical trials to other entities that are testing out Nanoknife on different cancers. As we've seen, VU University in the Netherlands is testing Nanoknife electroporation on liver cancer, and CROES on a large 200-patient prostate cancer trial. ANGO is directly sponsoring a smaller 14-patient Phase I prostate cancer trial with Nanoknife estimated to be complete in March 2014.
ANGO has been breaking even for several years as a company licensing Nanoknife and other technologies, but it has not yet succeeded in pulling away. The stock is once again testing its $10 support zone, so if you want to bet on Nanoknife cancer success in March, now would be a good time to take a long position. The only caution is that the company has recently taken up significant debt at 40% market cap suddenly this year after being relatively debt free, so if these upcoming Nanoknife trials fail, it could spell trouble for ANGO.
As for Inovio, this company is further along the pipeline in Phase II with a goal of 148 patients, going after an electroporation delivered cervical cancer vaccine. This trial is quite large for a Phase II cancer trial and success could mean big things for INO. But keep in mind that its electroporation system has failed in the past with head and neck cancer, previous Phase III trials that were suspended.
The positives are that Inovio has zero debt. On the negative side, it has an accumulated deficit of over $230 million and a history of failure. Nevertheless, March 2014 could be a big month for the company. Finally, Scancell, a company on the London exchange, is conducting a Phase I/II study on melanoma which looks especially promising. Plasmid DNA called SCIB1 is being electroporated intramuscularly into melanoma tumors to stimulate T-cells to attack. This phase II trial includes 30 patients who took different doses of the immunotherapy drug. According to a December Scancell press release:
One patient in the 4mg dose group had a long history of metastatic disease and multiple tumour lesions present at the start of treatment (including several in her lungs), all of which decreased in size or disappeared completely following six months of treatment with SCIB1 except for one abdominal tumour nodule which increased in size and which will be resected. This "differential response" pattern is typical of immunotherapeutic agents and is the first signal that SCIB1 may be having an impact on the course of the disease as well as inducing an immune response.
The most investable companies pursuing electroporation cancer treatments in my opinion are OncoSec, AngioDynamics, and Scancell. OncoSec because of its very positive Phase I results and imminent Phase II for merkel cell cancer, zero debt, and high upside. Angiodynamics because of its consistent break-even stable finances and current testing of support, the fact that Nanoknife is already selling and approved for some uses, and its upcoming Phase II results for prostate cancer less than a year away. Scancell has some very impressive results so far and is seeking a buyer when phase II is complete by the end of this year. Given its impressive results for SCIB1, it may be picked up by a big player. If that happens, shares could skyrocket. Inovio is also an option, though past failure with head and neck cancer advises caution there.