New means of drug administration often escape the attention of investors in the biotech arena as they may seem to be irrelevant, expensive or inferior to existing methods. Additionally, they are simply unproven and would require years of clinicals before safety and efficacy are proven to regulatory agencies and physicians. An emerging means of administering a chemotherapy agent, ElectroChemotherapy is a novel use of a tried and true technology termed electroporation. In electroporation, an electrical current is applied across two electrodes, which stimulates the cells within a certain area (often expressed in cubic centimeters) between the two electrodes. Irreversible electroporation is a type of ablation in which enough current is applied for an extended period of time killing the cells, most notably cancer cells which are typically easier to kill while the healthy normal cells are more able to recover. The same concept applies via cytotoxic agents (chemotherapy) and radiation treatments in which the faster growing cancer cells are more susceptible to many of these treatments while the healthier cells can more readily resist and recover from exposure of the cancer treatments.
A more modern approach to using electroporation, however, is a reversible electroporation technique in which a current is temporarily applied to cancer tumors which increases the porosity of the cell's membranes and allows pre-injected chemotherapy or immunotherapy agents to readily permeate the cancer cells. The applied current is then removed, and the cell membranes pores close back up trapping the agents inside the targeted cells. This has the multiple benefits of increasing efficacy, reducing systemic exposure as the cytotoxic agents are mostly trapped within the targeted cells and reducing costs as much less of the agent is required than via the traditional approach in which the drug is "diluted" in the patient's bloodstream. Although the concept sounds fairly simple, it is a fairly under the radar technology that has had a great deal of success in the last decade but will likely gain more investor attention in the coming months as additional clinical data becomes available and publicly-traded companies are identified with some level of knowledge, experience and even clinicals underway for this now-budding treatment option for cancer patients.
The list of small pharma that have solid experience with electroporation technology for fighting cancers is a short one. Even shorter is the list of publicly-traded companies with experience in the field. Following is a brief summary of the latter followed by excerpts from various sources revealing the use of the therapy over the last decade. In many of these cases the trials are performed on very small scales and/or by universities both in the U.S. and abroad. Although the trials may not have been run for any type of regulatory approvals or via the necessary controlled parameters, they do help to legitimize the electroporation approach to fighting cancer. They can also help give investors some knowledge and insight into the technology and allow them to make educated investment decisions on the platform and associated companies. Each of these companies appears to be relevant and could have solid returns for investors if the technology begins showing clinical success due to the large marketing potential with many forms of cancers potentially targeted with the novel chemotherapy drug administration.
Companies Leading the Charge Against Cancer via Electroporation
Inovio Pharmaceuticals (INO) has been on the forefront of the electroporation administration of both chemotherapy agents and immunotherapy agents for the fight against cancer. It has licensed its technology to several entities including The University of Southampton (UK), Tripep AS, The HIV Vaccine Trials Network (HVTN), The University of Pennsylvania, The National Institute of Allergy and Infectious Diseases, The Path Malaria Vaccine Initiative, The U.S. Army and The National Cancer Institute. It stands to be a huge player in the technology in the upcoming years as its platform could become more proven and have data from either of these entities to support additional licensing or sales to other pharmaceuticals. A development-Phase company, investors should note that the company's most advanced candidates are in Phase II clinicals. Although hopeful in many of their drugs, the downside for the company is also great as a failed trial not only means a likely drug failure, but all the time and money invested in the treatment would have been a loss as well.
Merck (MRK) is developing its Plasmid V930 Phase I candidate for treating breast, ovarian, non-small cell lung and colorectal cancers. The vaccine is being delivered by Inovio s electroporation MedPulser DNA Delivery System to deliver the therapeutic DNA vaccine into muscle tissue to enhance the expression of HER2 and CEA antigens and increase the body's immune response to cells with these overexpressions. Merck has already paid Inovio a $2 million royalty payment for its IND filing in 2005 and could be paying them additionally as the trials for the vaccine progress. This kind of licensing is key to Inovio's success as it provides the company with solid revenue while minimizing the risks associated with development costs and setbacks should any occur. A solid investment bet due to its diverse and successful pipeline, the $132 billion company doesn't likely represent huge upside for investors solely due to possible success in the electroporation application. However, investors wanting safer exposure to possible future successes in the novel treatment could consider this company.
OncoSec Medical (OTCQB:ONCS) has put its future on the line utilizing electroporation as a means to administer both chemotherapy and immunotherapy agents in its fight against cancer. It licensed its electroporation technology also from Inovio with an agreement announced on March 2011. The company's entire pipeline is based on using the technology aptly renamed by OncoSec as OMS ElectroImmunotherapy and OMS ElectroChemotherapy. The company has done very well since obtaining the technology with Phase III data for its OMS ElectroChemotherapy for Head and Neck Cancer expected to be presented on July 22-24. It has a catalyst-filled 2012 ahead of it via its ElectroImmunotherapy platform with Phase II interim data for metastatic melanoma, Phase II interim data for Merkel cell carcinoma and enrollment initiation for a Phase II trial for the treatment of cutaneous T-cell lymphoma by the end of the year. With the smallest market cap of the three at $23 million, the upside is greater here with real or perceived success in any of these catalysts. However, its financials are weak compared to Merck and Inovio with its entire future potentially on the line through this year's catalysts. Success or failure would either prove to be huge share price movers, although in opposite directions. OncoSec is hedging its bets by having the two different types of agents in clinicals with its ElectroImmunotherapy approach using interleukin-12 (IL-12) and its ElectroChemotherapy approach currently utilizing bleomycin as agents of choice. Adding to its potential is the large numbers of other agents that may be substituted for either of these approaches giving a virtually unlimited number of cancers it could target with a host of immunotherapy and chemotherapy agents.
Harvard Bioscience (HBIO) is a scientific instrumentation company that stands to gain from increased popularity of electroporation use for many indications including cancer. In 2004 they launched their BTX MOS 96 well electroporation system. They expanded their product line via a licensing agreement with Cellectis in 2010 granting them worldwide use of Cyto Pulse electroporation-based instruments. The instrumentation already has widespread use in genetics with in vivo, in ovo and in vitro gene delivery, electrocell fusion and nuclear transfer cloning. Increasing use of the platform for chemotherapy and immunotherapy agent transfer into cancer cells' interiors will only add to the company's bottom line as the technology progresses. Additional clinical success over time would certainly benefit the company while clinical failures would only mean fewer additional units sold while still having revenue gained already in hand. Fisher Scientific (TMO) is currently one of the marketers of the BTX systems and would also benefit from the technology's increased usage. However, the investment upside here would be minimal for this $19.4 billion behemoth. A couple of the BTX units may be viewed on Fisher's website and indicate the profitability and cost effectiveness of the technology if the BTX unit is a comparable price to the ones used in clinicals with price tags here of only about $13K.
Legitimizing the Technology for Fighting Cancers - Brief Excerpts for Investor Due Diligence
Following are some excerpts for investor research purpose. As indicated earlier, the technology seems fairly straight-forward, but many investors may not be familiar with it. The entities performing the following trials range from universities to public and privately-held companies. The summaries presented are merely examples of earlier work in this emerging field and are given to partially validate the technology and give investors additional knowledge on applications of the electroporation platform. The agents utilized range from chemotherapy to immunotherapy agents administered via electroporation.
- Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy Objective responses were obtained in 233 (85.3%) of the 273 evaluable tumours that were treated with ECT. Clinical complete responses were achieved in 154 (56.4%) tumours, and partial responses were observed in 79 (28.9%) tumours. The application of electric pulses to the patients was safe and well tolerated. An instantaneous contraction of the underlying muscles was noticed. Minimal adverse side-effects were observed.
- Treatment of hepatocellular carcinoma in a rat model using electrochemotherapy. Dose response data were obtained for both electric field intensity and Bleomycin (Bleomycin is currently the agent of choice also for OncoSec's ElectroChemotherapy trials) Complete response rates for animals treated with electrochemotherapy ranged from 26.67% to 93.33 and were durable. In contrast, tumours that received no treatment, pulses only or drug only responded minimally. This supports the feasibility of using a ECT as a modality for treating hepatocellular carcinoma.
- A cost-effectiveness analysis was carried out on ECT using the Cliniporator vs. other techniques ECT is cost-effective with an incremental cost effectiveness ratio (ICER) of €1,571.53 to achieve a further additional response. Radiotherapy and interferon-alpha are the least effective strategies. A combination of hyperthermia, chemotherapy, radiotherapy, and interferon-alpha treatment are dominated by ECT (more costly and less effective). Isolated limb perfusion is the most effective treatment, but is very costly (€18,530.47) because of the use of antiblastic drugs (TNFα), with an ICER of €92,717.29…. After sensitivity analysis, the study results confirm the favorable cost-effectiveness ratio of ECT with the Cliniporator and justify its wider use.
- Efficient Responses in a Murine Renal Tumor Model by Electroloading Dendritic Cells With Whole-Tumor Lysate. Mice treated with electroloaded DCs had a 50% reduction in lung metastases compared with control mice that received no DCs or DCs loaded with liver lysate.