<><><><><>
 
History image

 

History

CEL-SCI's story is one of vision, persistence, and survival in the face of overwhelming odds. Despite downturns in the biotech sector, lack of funding, and a lengthy clinical trial process associated with the development of its investigational therapy for advanced primary head and neck cancer, CEL-SCI is finally approaching the end game! Our lead investigational immunotherapy, Multikine (Leukocyte Interleukin, Injection), has been tested in Phase I and II clinical trials, and is now enrolling patients for a global Phase III trial. Multikine (Leukocyte Interleukin, Injection) is the full name of this investigational therapy, which, for simplicity, is referred to in the remainder of this page as Multikine*.

The story began at the Max Plank Institute in Germany in the late 1970s, with science and research supporting the theory that the immune system could fight cancer. Maximilian de Clara, the Company's founder, believed strongly that the immune system played an important role in fighting this disease, but he lacked the technology to turn his idea into a product. A visionary and successful entrepreneur, Maximilian was not easily discouraged. He funded the early Multikine research at the Max Plank Institute in 1978, founded CEL-SCI around the idea of Multikine in 1983, took the Company public soon thereafter and located it at the office of the Company's patent attorney in the Washington, D.C area.

Dr. Dudley Dumonde, the renowned scientist who coined the term "cytokine" (Multikine contains a mixture of cytokines), conducted the first clinical trials for CEL-SCI between 1985 and 1988 in England. Until 1992, CEL-SCI was cash poor and struggling to survive. The technology necessary to manufacture Multikine as a biological drug product on a sufficient scale suitable for conducting widespread studies in humans (and ultimately to support commercialization if regulatory approval were secured) only became available in 1993. It was then that CEL-SCI committed to the full commercial development of Multikine. Professional management and scientific personnel were hired, a research laboratory was built and a small pilot plant manufacturing facility was constructed.

We firmly believed that for a potential immunotherapeutic agent to have a greater likelihood of activating an anti-tumor immune response, it had to be administered first-line, before the administration of traditional therapies (such as chemotherapy, surgery and radiation) when the immune system may be more intact. This caused us to aggressively pursue research and development of this investigational therapy to support a potential first-line indication for advanced primary head and neck cancer. The strategy was controversial because physicians had to be convinced to assess first-line use of the investigational Multikine therapy, which meant using an experimental drug, Multikine, before using any other proven therapies. Then, multiple and lengthy clinical trials had to be conducted, as is the case for any new medicine, but which naturally prolonged the product development cycle. CEL-SCI persisted with its belief, despite the delays and additional complexities.

From 1994 to 2000, CEL-SCI completed a series of Phase I and Phase II clinical trials (in humans) with Multikine. In 2001, a lengthy and costly manufacturing process validation was completed, which provided a high level of scientific assurance that CEL-SCI could reliably and reproducibly manufacture a product that could meet necessary requirements and specifications. Completion of the manufacturing process validation for the investigational Multikine therapy was a very important achievement for CEL-SCI for two reasons: not only was it a necessary, long-term step prior to being able to produce the product for commercial distribution (if it were approved for marketing, e.g., by the FDA), but it also helped minimize our business risk and enhanced our ability to compete successfully in the marketplace if this investigational therapy ultimately were to be approved.

Unfortunately, the following year saw the collapse of the biotech sector, sending CEL-SCI back into survival mode as funding dried up sector-wide. CEL-SCI soldiered on and spent the next few years publishing an extensive body of data from Multikine studies in peer reviewed scientific journals. Representative of the published data were the following publications:

  o Findings suggesting that Multikine has the potential to enhance the effectiveness of chemotherapy and radiation in the "Laryngoscope" journal (2003).  
       
  o A presentation of Multikine Phase II data at the annual "American Society of Clinical Oncology" meeting (2004).  
       
  o Multikine's mechanism of action and immunological data from animal studies (Chirigos et al Immunopharm. and Immunotox. 1995) and in human studies (Timar et al JCO 2005).  
       
  o A follow-up report from the final Phase II study in patients, in which Multikine was reported to have an approximate 33% increase in overall survival at 3.5 years after surgery over the overall survival which could be gleaned from review of 55 peer-reviewed publications, in the same patient population, published between 1987 and 2007. These data were presented and published in the "Oral Oncology" (2007).  

No definitive conclusions can be drawn from these data about the safety or efficacy profile of this investigational therapy, and further research is required and the global Phase III study is ongoing in an effort to confirm these results.

Things began to improve again in August of 2005, when Canada became the first country to clear Multikine to enter Phase III trials. The US followed in January 2007 and enabled this investigational therapy to enter a Phase III clinical trial. In addition, the FDA designated Multikine as an orphan drug in 2007 for the orphan population of neoadjuvant treatment of patients with squamous cell carcinoma of the head and neck. This was a great achievement because the status qualified CEL-SCI for a number of very significant incentives, including:

  o Seven years marketing exclusivity from the date Multikine is approved or licensed.  
       
  o Possibility that approval time for Multikine could be expedited or accelerated.  
       
  o The opportunity to apply for an Orphan Grant, providing up to $350,000 per year for up to 3 years.
 
       
  o Tax incentives of up to 50% of clinical investigation costs associated with Multikine's development.
 

In August 2006, CEL-SCI raised $8.3 million and followed that up with another $15 million in equity capital in April 2007.  In August 2007 CEL-SCI announced a deal with a real estate investment group to build a 73,000 square foot manufacturing facility for Multikine. In October 2008, CEL-SCI took possession of the new facility. 

The financial crisis of 2008 and 2009 hit CEL-SCI very hard and led to significant delays in finishing the validation of the manufacturing facility and the start-up of the Phase III clinical trial. However, management pulled together, continued forward without salaries and funded CEL-SCI with its own money through these difficult times. The second half of 2009 brought significant improvement and allowed CEL-SCI to raise significant monies. This marked the first time ever that CEL-SCI was properly financed to do its work. With these funds in hand CEL-SCI prepared its global Phase III clinical trial for Multikine. CEL-SCI hired an experienced Clinical Research Organization to run this global study. However, in April 2013 CEL-SCI had to transfer the management of its Phase III trial for Multikine in the treatment of head and neck cancer to two new CROs because, among other things, the prior CRO, which was hired at the Study initiation, did not achieve the rate of patient enrollment in our study assumed by our contract, and the CRO had a high internal rate of turnover among their personnel which negatively affected the conduct of our Phase III trial. CEL-SCI believes that the new CRO team is now effectively managing the Phase III trial. Full enrollment in the Phase III study is anticipated to occur by the end of 2015.

Significant opportunities presented themselves in late 2013 which allowed CEL-SCI to pursue additional indications for Multikine. CEL-SCI signed a CRADA (Collaborative Research and Development Agreement) with the U.S. Navy for the treatment of HIV/HPV co-infected patients with anal warts. This collaboration could turn out to be very significant for us in the future.

Under the CRADA, the U.S. Navy is funding a clinical study to evaluate the safety and clinical impact of Multikine as a treatment for peri-anal warts and assess the effect on anal intraepithelial dysplasia (AIN) in HIV/HPV co-infected patients who are eligible for medical care from the Naval Medical Center San Diego. CEL-SCI is contributing Multikine, will retain all rights to any currently owned technology and will have the right to exclusively license any new technology developed from the collaboration.

Anal and genital warts are commonly associated with the Human Papilloma Virus (HPV), the most common sexually transmitted disease. The U.S. Centers for Disease Control and Prevention (CDC) has named HPV the 4th largest health threat the U.S. will face in 2014. According to the CDC, about 360,000 people in the U.S. get genital warts each year. Persistent HPV infection in the anal region is thought to be responsible for up to 80% of anal cancers. HPV is an even more significant health problem in the HIV infected population as individuals are living longer as a result of greatly improved HIV medications, but are mostly unable to clear HPV due to their weakened immune system. Patients with anal warts who are co-infected with HIV/HPV have about a 30-fold increased risk of developing anal cancer because their compromised immune system.

Our new CRO Ergomed understood the importance of our collaboration with the U.S. Navy and signed two co-development agreements with CEL-SCI sharing the development expenses for HPV disease in HIV immune suppressed patients on a 50/50 basis, providing up to $6 million in funding for these trials. These new indications which are being explored may potentially allow us to more quickly bring Multikine to market as an immune therapy should it be proven safe and effective in treating these diseases. Ergomed is also contributing up to $10 million to the Multikine Phase III study in head and neck cancer. This money will be repaid in the form of royalties, up to a certain amount, from sales of Multikine once it is approved for commercial use.

Now that the Multikine pivotal Phase III trial is moving forward again, the Navy is moving forward with its separate Multikine study and CEL-SCI is armed with $34 million in new capital raised in late 2013 and early 2014, CEL-SCI is again able to focus on the execution of the Phase III study in order to be able to conclusively demonstrate to the FDA and other regulatory agencies that the investigational Multikine therapy could be beneficial for the use in the treatment of advanced primary head and neck cancer patients.

Biotech research and drug development is a long and arduous road. CEL-SCI has endured the biotech boom and bust cycles, and our committed team has persisted because of the strength of our belief in the promise of Multikine to change the way we treat cancer. We have never taken any shortcuts in our research or product development, nor have we given up major marketing rights or control of Multikine to licensees because we strongly believe in preserving the greatest value for CEL-SCI's shareholders. We are extremely excited about what we currently anticipate is the final phase of the clinical development of Multikine, and we hope to build a great company that will serve patients, doctors and shareholders alike.

 

* Multikine is the trademark that CEL-SCI has registered for this investigational therapy, and this proprietary name is subject to FDA review in connection with our future anticipated regulatory submission for approval. Multikine has not been licensed or approved for sale, barter or exchange by the FDA or any other regulatory agency. Similarly, its safety or efficacy has not been established for any use. Moreover, no definitive conclusions can be drawn from the early-phase, clinical-trials data summarized on this page or elsewhere on this website involving the investigational therapy Multikine (Leukocyte Interleukin, Injection). Further research is required, and early-phase clinical trial results must be confirmed in the well-controlled, Phase III clinical trial of this investigational therapy that is currently in progress.