Potential Indications of our Investigational Therapy Multikine® (Leukocyte Interleukin, Injection) to the Medical Community

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.

Potential first-line immunotherapy: Multikine is an investigational immunotherapeutic agent being developed as a potential therapeutic agent directed at utilizing the ability of the immune system to produce an anti-tumor immune response. The first indication we are pursuing for our Multikine product candidate is for the neoadjuvant therapy used as first-line treatment in newly diagnosed patients with advanced primary squamous cell carcinoma of the head and neck, or SCCHN. SCCHN is a type of head and neck cancer. In Phase I and Phase II clinical trials and in the recently completed Phase III clinical trial, Multikine was administered prior to any other cancer therapy because CEL-SCI believes that this is the period when there is a greater potential likelihood of activating an anti-tumor immune response. Once the patient has had surgery or has received radiation and/or chemotherapy, the immune system may become weakened and may be less able to mount an anti-tumor immune response.

Other immunotherapies have historically been administered later in cancer therapy (i.e., after radiation, chemotherapy, surgery). Many scientific leaders in the field think that immunotherapy should be used early in the disease process and a combination of therapies may be needed to overcome cancer.

Potential Implications of First-Line Treatment:

The current standard of care (SOC) first-line treatment regimen for advanced primary (i.e., not yet treated) head and neck cancer patients consists of surgical resection of the tumor and involved lymph nodes, followed by either radiotherapy alone or radiotherapy and concurrent chemotherapy as recommended by the NCCN Clinical Practice Guidelines in Oncology issued by the National Comprehensive Cancer Network based in part on the RTOG and EORTC studies in the same patient population (NEJM 2004). The recently completed Multikine Phase III trial tested the hypothesis that Multikine treatment, administered right after diagnosis and prior to the SOC treatment regimen, will improve overall survival as compared to SOC control, enhance the local/regional control of the disease and reduce the rate of disease progression in patients with SCCHN. Our Phase 3 results demonstrated that Multikine given before surgery and radiation produces a significant 5-year survival benefit. Globally about 210,000 patients p.a. could have the potential to benefit from this new finding.

Safety reports from Phase 1 and Phase 2 clinical trials (as reported by the clinical investigators): During the early investigational phase, in Phase I and Phase II clinical trials in over 220 subjects who received the investigational therapy Multikine in (daily) varying doses from 200 to 3200 IU as IL-2, no serious adverse events were reported as being expressly due to administration of this investigational therapy. The most frequently reported adverse events included pain at the injection site, local minor bleeding and edema at the injection site, diarrhea, headache, nausea, and constipation. No “abnormal” laboratory results were reported following Multikine treatment – other than those commonly seen by treating physicians in this patient population – regardless of the dose of Multikine administration. Similarly, in these early-phase clinical studies, in patients, there was no reported increased toxicity of follow-on treatments (as a result of Multikine administration). No complications following surgery (such as increased time for wound healing) were reported. The report from the Phase III study indicated no safety issues associated with Multikine administration.

Potential effect on recurrence of cancer: Tumor cells can persist after treatment with radiation, chemotherapy and surgery. The persistence of these cells is thought to be partly responsible for cancer recurrence. Multikine is injected around the tumor and in the vicinity of the local lymph nodes because these are the areas where metastases are believed to be most likely to develop and where the cancer may recur. We believe that the Multikine investigational treatment may enable the immune system to destroy those tumor cells before they can cause tumor recurrence. Other therapies have been approved for use in patients with recurrent/metastatic disease. These other therapies are not for the same patient population for which CEL-SCI’s Multikine is currently being developed.

Off the shelf product / does not need to be customized: The investigational Multikine therapy is mass-produced for clinical investigations under Good Manufacturing Practices and is being developed as a potential ready-to-use anti-cancer immunotherapy for advanced primary head and neck cancer. As opposed to certain cancer vaccines, Multikine does not need to be customized or developed from the patient’s own cancer, immune or other cells.

Multikine investigational therapy is developed and manufactured in a dedicated manufacturing facility

The facility is located outside Baltimore, Maryland, USA, a commercial size cGMP Drug Production facility dedicated to Multikine.
The facility includes a True Cold Fill (approx. +4°C) capability to avoid loss of biological activity during fill, and was constructed to meet US and European regulations.
The facility supplied Multikine investigational therapy for the Phase III study, and, subject to regulatory review and approval of CEL-SCI’s Biologic License Application , will supply Multikine for commercial sale – .

Early-phase data suggests Multikine potentially has combination immunotherapy activity: Multikine may have the potential to simultaneously present both active and passive properties to act against the cancer cells (Timar et al. Laryngoscope 2003 and JCO 2005). These combined activities would seem to suggest that the activity of Multikine potentially could closely resemble the activity imparted by a healthy person’s immune system, which can monitor for and take action against cancer cells.

One immunotherapy vs. a mixture of immunotherapies: The Multikine investigational therapy is a defined combination (mixture) of natural cytokines; each of its molecular components is present in similar proportions as would be seen if it were secreted directly by the cells of a person with a healthy immune system. Thus, we believe that we are delivering the right proportional combination of the immunotherapeutic cytokines to the patient.

Potential treatment in HIV/HPV co-infected patients: CEL-SCI conducted a Phase I study of Multikine in HIV/HPV co-infected men and women with peri-anal warts at the Naval Medical Center (San Diego) and at the University of California, San Francisco. The purpose of this study was to evaluate the safety and clinical impact of Multikine as a treatment on peri-anal warts and assess its effect on anal intraepithelial dysplasia (AIN) in HIV/HPV co-infected men and women.

CEL-SCI’s focus in HPV is not the development of an antiviral against HPV in the general population. Instead, it is the development of an immunotherapy to be used in patients who are immune suppressed by diseases such as HIV and are therefore less able or unable to control HPV infection and its resultant diseases. These patients have no viable treatment options available to them. HPV is also relevant to the head and neck cancer in the Phase III study since it is now known that some strains of HPV are associated with and may cause head and neck cancer. Multikine was shown to be able to kill, or eliminate, a number of strains of HPV (as determined by HPV-PCR) in a Phase I study of Multikine in HIV/HPV co-infected women with cervical dysplasia.

Potential role in multiple tumors to be explored in future R&D: Preliminary data from the ongoing clinical development program for the Multikine investigational therapy suggests that it may have a potential role in other cancers. Because the Multikine investigational therapy already has shown preliminary biological activity in very early-phase clinical studies in both cervical dysplasia/neoplasia and prostate cancer, CEL-SCI intends to pursue further R&D to investigate these potential roles in the future.

* 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 by any other regulatory agency. Similarly, its safety or efficacy has not been established for any use.