Editors' Note: This article covers a stock trading at less than $1 per share and/or with less than a $100 million market cap. Please be aware of the risks associated with these stocks.
With recent news of an upcoming clinical trial, CEL-SCI Corporation (NYSEMKT:CVM) proves to be one of the best bets on the fast track of immunotherapy, drugs using the body's own natural defenses to fight disease. Its latest win is approval from the US Navy to begin a dose escalation Phase I study using Multikine, the company's proprietary version of small proteins that regulate immune response and inflammation, in men and women suffering from both HIV and human papilloma virus (HPV) that have developed unsightly and potentially dangerous warts around the anus. HPV is particularly insidious because of the lack of overt symptomology, making it the commonest of sexually-transmitted diseases.
Just last fall, CEL-SCI signed a Cooperative Research and Development Agreement (CRADA) with the Naval Medical Center in San Diego, CA, a center of excellence in HIV and AIDS care with more than 30 clinical trials done to date, for a human study pursuant to approval from the Navy's Institutional Review Board (IRB) consisting of a body of experts that sanction clinical trials. This has been achieved, allowing immediate patient enrollment. Along with peri-anal warts, Multikine's effect on anal intraepithelial dysplasia, a forerunner to anal cancer, will be measured. The study will not take long with results expected this year.
Initial patients will be treated and observed for six weeks; if side effects are not severe, additional subjects will be added at a higher dose. CEL-SCI plans to leverage the clinical trial design of a Phase I study done at the University of Maryland in cervical dysplasia in those co-infected with HIV and HPV, where administration of Multikine resulted in lesion reduction and the elimination of some HPV strains, of which up to150 exist with varying degrees of cancer potential. Importantly, CEL-SCI is not required to relinquish patent rights, does not owe money to the Navy and stands to exclusively license any new technology, if developed.
When safety is shown, effectiveness in eradicating anal warts with Multikine may be explored to see whether the drug works by jump-starting the immune system to halt HPV from evolving into cancer. A known 40 of the universe of HPV strains can easily spread through direct skin contact during sex, be it vaginal, anal or oral, and left untreated, infection develops into cancer in 5% of cases worldwide. Virtually all cervical cancers are caused by HPV infection. The strong correlation between anal warts and anal cancer aside, men and women also infected with HIV/HPV increase their risk of anal cancer substantially due to a compromised immune system.
According the Center for Disease Control (CDC), prevalence of Americans with HPV is 79 million with an annual incidence of another 14 million. It is estimated that nearly every sexually-active person will acquire one form of HPV in their lifetime. The incidence of anogenital warts and cervical cancer are 360,000 and 10,300, respectively. Medicine views peri-anal warts as a harbinger of cancer, thus a high level of interest in Multikine as a potent immune system compound to suppress HPV persists among researchers and practitioners alike.
With the Navy on board, CEL-SCI now pursues three indications for Multikine, making it a true technology platform where information from any one set of trials can further knowledge of mechanisms of action and potentially hasten time to commercialization. The company got a big boost when internationally-renowned contract research organization, or CRO, Ergomed signed on as a co-developer of clinical trials in HIV/HPV infected women with cervical dysplasia last October. Within two weeks, Ergomed then agreed to help fund studies of co-infected individuals with peri-anal warts. CEL-SCI is now in a position to move more rapidly with enrollment in these studies, in addition to receiving Ergomed's aid with its landmark Phase III trial using Multikine in head and neck cancer. Ergomed's total commitment is approximately $16 million to be repaid from future potential sales of Multikine, quite a statement of belief in the ultimate success of the drug.
CEL-SCI seeks to make its Phase III trials in primary head and neck cancer, its most advanced study, the largest in the world with expected enrollment of almost 900 patients in 100 sites in 20 countries, including the US. The latest to grant approval is Serbia, bringing the total to 11 countries so far, with Ergomed about to initiate clinical efforts there within weeks. Head and neck cancer is aggressive, affecting 600,000 people globally per year; 92% of cases present outside of the US, most of them with Stage III disease and a solid reason for CEL-SCI to conduct trials in territories outsides of the US. Multikine would become the first anti-cancer agent using immunotherapy as a first-line defense before surgery, radiation and chemotherapy and with the speed that countries are allowing studies to begin, it appears that regulatory bodies everywhere acknowledge Multikine as holding the potential to address a serious unmet medical need where no other exists. CEL-SCI's shares were hurt badly when the company had to replace a prior CRO running its Phase III Multikine trial for head and neck cancer, and the fact that Ergomed is rapidly filling clinical trial patient slots should be seen as a bullish sign for CEL-SCI.
Central to CEL-SCI's success in gaining quick clinical trial approval for head and neck cancer was a highly favorable development last November when an Independent Data Monitoring Committee (IDMC) comprised of scientific experts analyzing safety data from the company's Phase III concluded that Multikine's lack of adverse side effects warranted continuing with the current study design, spurring an escalation in efforts to expand pivotal trials to more sites.
Immunotherapy in cancer, using the body's own cells to fight disease, is a promising area of scientific research. Simply put, the immune system of cancer patients has been tricked by the disease not to see cancer cells, allowing tumor growth to escape the immune system's attention. Multikine changes that by making the tumor visible to the immune system. And since Multikine is given before radiation and chemotherapy, the patient's immune system is still relatively healthy and therefore able to destroy cancer cells when recognized. Early efforts explored interleukin-2 stimulation on metastatic melanoma and renal cancer, with an astounding 50% of subjects experiencing complete tumor regression and 80% remaining cancer-free after 20 years; it was later concluded that immunotherapy administered systemically may constitute a highly effective treatment like no other. Currently, immunotherapy is coupled with other traditional methods but Multikine, if effective in head and neck cancer, would present a brand new opportunity to oncologists.
CEL-SCI is a pioneer in clinical connections between HPV and head and neck cancer. HPV infects epithelial cells, tissue that lines skin and body cavities like the throat, genital area and anus. HPV does not enter the bloodstream so an infection in one part of the body would not be transferable unless direct contact is made. Education intended to prevent intercourse-induced STDs has most likely led to oral means of sexual satisfaction with participants hoping to avoid HIV and other serious intimacy-related infections, but may be contributing to the rise in oropharyngeal cancer, a subgroup of head and neck cancer; indeed, the US is now seeing a rapid increase in head and neck cancer in younger people due to HPV infection. Researchers estimate that by 2020, oropharyngeal cancer will outpace cervical cancer caused by HPV.
Investment in micro-capitalization companies, those under $100 million trading under $1.00 per share, carry unique risks that typically consist of low volume and sparse news flow. CEL-SCI mitigates these risks with an average three-month trading volume of over 1.5 million shares, and by diligently informing investors of company developments. Attention will now be focused on CEL-SCI's new set of Phase III trials with Multikine in head and neck cancer, with an eye toward more rapid patient enrollment than in the past. Whether the new trials can produce similar results to earlier ones is a major risk to buying this stock, but if the company proves successful, a large return is possible.
CEL-SCI has been successful in raising funds since last October, with an estimated $22 million added to the balance sheet under a very conservative burn rate. Reassuring results from past Multikine trials, no history of regulatory trouble, two positive endorsements from the IDMC and the fact that all of the diseases that CEL-SCI treats represent unmet medical needs should act as a modifier for the company's potential perils. Competition in the form of Gardasil, a vaccine by Merck & Co. (NYSE:MRK) recommended for early teenagers to prevent HPV is the only viable therapeutic solution to date and found to be effective in only one-tenth of the virus' strains.
Undertaking two new clinical trials in different indications, as well as conducting the largest study in head and neck cancer with accelerated enrollment aided by its new development partner, CEL-SCI has the potential to stir up the medical community with Multikine as a cancer immunotherapy directed to reduce tumor recurrence and increase survival as well as provide an innovative treatment for HIV/HPV infection and address their associations with cancer. Catalysts for news flow have been constant, keeping investors interested in this company intent on transforming the face of cancer therapy as Multikine moves closer to market.