History

CEL-SCI’s story is one of vision, persistence, and survival in the face of overwhelming odds. The story began at the Max Planck 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 the 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 1995 to 2004, CEL-SCI completed a series of Phase 1 and Phase 2 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 the 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 was 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. A representative of the published data were the following publications:

• Findings suggesting that Multikine has the potential to enhance the effectiveness of chemotherapy and radiation in the “Laryngoscope” journal (2003).
• A presentation of Multikine Phase 2 data at the annual “American Society of Clinical Oncology” meeting (2004).
• 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).
• A follow-up report from the final Phase 2 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 a 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 could be drawn from these data about the safety or efficacy profile of this investigational therapy, and further research was required. That is why the global pivotal Phase 3 study was needed.

The US cleared the Phase 3 trial in January 2007. 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:

• Seven years marketing exclusivity from the date Multikine is approved or licensed.
• The possibility that approval time for Multikine could be expedited or accelerated.

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. This was deemed to be necessary based on consultation with the FDA for eventual drug approval even though Multikine was still an experimental drug. 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 Phase 3 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 3 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 3 trial for Multikine in the treatment of head and neck cancer to two new CROs because, among other things, the prior CRO, was not enrolling patients as had been contracted.  The two new CROs achieved full study enrollment of 928 patients in September 2016, several years later than had been projected and agreed to with the first CRO.

In 2013 CEL-SCI filed an arbitration against Inventiv, the prior CRO.  This arbitration was funded by a litigation funding firm in 2015. In June 2018 the arbitrator ruled that Inventiv had materially breached the contract with CEL-SCI.

CEL-SCI continued to be almost exclusively focused on the execution and completion of the Phase 3 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. Now that we have seen excellent Phase 3 results in the treatment arm that receives surgery and radiation, but not chemoradiotherapy after surgery, we are extremely excited about filing for drug approval with the FDA, and 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 clinical trials data summarized on this page or elsewhere on this website involving the investigational therapy Multikine (Leukocyte Interleukin, Injection).