What is the investigational therapy Multikine® (Leukocyte Interleukin, Injection)?

INTRODUCTION TO INVESTIGATIONAL THERAPY MULTIKINE

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*. Multikine has not been licensed or approved by the FDA or by 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 this investigational therapy.

Multikine is an investigational immunotherapeutic agent being developed as a potential treatment for head and neck cancer, and cervical dysplasia or peri-anal warts in HIV/HPV (human immunodeficiency virus / and human papillomavirus) co-infected patients. The first indication we are pursuing for Multikine is an indication for neoadjuvant therapy in patients with squamous cell carcinoma of the head and neck, or SCCHN. In clinical studies conducted to date, and in our ongoing Phase III clinical trial, Multikine is administered prior to any other cancer therapy because it is generally accepted in the scientific community that this represents the period when the anti-tumor immune response still has the potential to be more fully activated. If it were to be approved for use following completion of our clinical development program, Multikine could be part of the next generation of cancer immunotherapy because:

• It is being developed as an off-the-shelf investigational therapy making large scale manufacturing at a reasonable cost possible;
• It is being developed with both active and passive immunity, which means that no external antigens are needed; and
•  It is being studied for administration prior to surgery, radiation and chemotherapy, when the immune system may be more intact and thus with greater potential to be activated.

Combination immunotherapy:

Combination immunotherapy may have the potential to most closely resemble the workings of the natural immune system in the sense that it could work on multiple fronts to potentially elicit or activate a response against cancer. Multikine investigational therapy has the potential to be a new type of immunotherapy. It is a defined mixture of cytokines (small proteins released by cells that have a specific effect on the interactions between cells). The cytokine mixture includes interleukins, interferons, chemokines, and colony stimulating factors; all of which are molecules which stimulate the body’s healthy immune response.  Multikine belongs to a new class of experimental immunotherapy called combination immunotherapy (i.e., it has both active and passive immune activity).

• Is thought to have the potential to cause a direct effect on tumor cells; and
• Is thought to have the potential to activate the immune system to produce an anti-tumor immune response.
• Multikine investigational therapy is a patented defined mixture of biologically active, natural cytokines, for which preliminary evidence from studies to date suggests the potential to simulate the body’s healthy immune response.
•  Cytokines are generally known to play a key role in regulating the body’s immune system.
• Multikine investigational therapy is not an autologous treatment, meaning it is not derived from and customized for the same patient. It is being developed and clinically studied as a ready-to-use, mass produced, off-the-shelf investigational therapy.
• Multikine is a patented defined mixture of 14 pro-inflammatory human cytokines. Many cytokines are approved for use in the treatment of cancer and are/have been used extensively.

Multikine investigational therapy is comprised of a mixture of cytokines; it is not one cell or one protein; it is a combination of molecules and proteins (interleukins, interferons, chemokines, and colony stimulating factors) derived from the stimulation in the culture of normal immune system cells.

• CEL-SCI is using this proven concept (cytokines in the treatment of cancer) to develop a more successful and less toxic cancer therapy by using the following concepts:

1. Multikine is administered locally, not systemically, in small supra physiological doses to avoid the serious toxicities previously seen with many cytokine treatments;
2. Multikine is administered while the immune system is still intact, with intent to improve the cure rate, while other cytokine treatment are generally used in recurrent cancer patients, and
3. Multikine combines cytokines in a manner similar to the way the body does it naturally as opposed to giving only one or two of them.

• Research at the US National Institutes of Health has shown that the cytokines in Multikine (shown in red in the table) are the ones that are required to reject any tumor
•  Injected for 3 weeks before any other cancer therapy around the tumor and near adjacent lymph nodes to stimulate the immune system to recognize the cancer cells and micro-metastases. Once the immune system is able to “see” the cancer, the still intact immune system does what it is meant to do – destroy the cancer.
• The goal is to kill the tumor micro metastases thought to be responsible for recurrence, thereby reducing cancer recurrence and increasing survival.

* 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 by the FDA or by 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.