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. 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.

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 patients newly diagnosed with 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 ongoing Phase III clinical trial, Multikine was/is being 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.

To date, other immunotherapies have 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:

  o The current standard of care, or SOC, first-line treatment regimen for advanced primary 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 and as recommended by the RTOG and EORTC (NEJM 2004). The ongoing Phase III trial is testing the hypothesis that Multikine treatment, administered 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. Subject to the successful completion of CEL-SCI's global Phase III clinical trial that is currently in progress and FDA's review of our entire data set on this investigational therapy, if FDA were to conclude that the safety and efficacy of this investigational therapy is established, the early-phase clinical data is encouraging in that they suggest the potential that approximately 60-66% (2/3) of head and neck cancer patients who present with advanced primary disease could possibly be candidates for this investigational therapy if it were to be approved by FDA.  
       

Safety reports from Phase I and Phase II 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) doses of 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 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. 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 ongoing in an effort to confirm these results.  Potential conclusions could only be drawn if the initial observations in the early-phase studies relating to the potential adverse events associated with Multikine administration and its potential efficacy in treating head and neck cancer are confirmed in the well-controlled Multikine Phase III clinical study, CEL-SCI's Phase III efficacy study is completed successfully, and the FDA licenses the product following their review of all of the data related to Multikine submitted in CEL-SCI's license application. 

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.

Off the shelf product / does not need to be customized: The investigational Multikine therapy is mass-produced for clinical investigations under current 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

  o The facility is located outside Baltimore, Maryland, USA, a commercial size cGMP Drug Production facility dedicated to Multikine.  
       
  o The facility includes a True Cold Fill (approx. +4C) capability to avoid loss of biological activity during fill, and was constructed to meet US and European regulations.  
       
  o The facility supplies the Phase III study Multikine investigational therapy, and, subject to regulatory review of CEL-SCI's application, will supply subsequent commercial sale - following the marketing approval of Multikine. The current capacity is estimated to be about 20,000 treatments annually, while the  fully built-out capacity will be approximately 60,000 treatments annually from the same facility.  
       

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, if confirmed, 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.

If, following completion of the pivotal global, well-controlled Phase III clinical trial and submission and FDA review of CEL-SCI's Multikine marketing application, this investigational therapy were to be approved for marketing, CEL-SCI would intend for it to be readily available as an "off-the-shelf" injectable preparation.

On August 14, 2017, CEL-SCI announced that it has received a letter from the FDA stating that the clinical hold that had been imposed on the Company's Phase III cancer study with Multikine has been removed and that all clinical trial activities under this Investigational New Drug application, or IND, may resume.

Nine hundred twenty-eight (928) newly diagnosed head and neck cancer patients have been enrolled in this Phase III cancer study and all the patients who have completed treatment continue to be followed for protocol-specific outcomes in accordance with the Study Protocol. The study's primary endpoint is a 10% increase in overall survival for patients treated with the Multikine treatment regimen plus Standard of Care (SOC) versus those who receive SOC only. The determination if the study's primary end point has been met will occur when there are a total of 298 deaths in those two groups. Current SOC for this indication is surgery, followed by radiation therapy alone or followed by concurrent radio-chemotherapy.

In the spring of 2016, the IDMC recommended to us that new patient enrollment should stop in the Phase 3 study, but patients already on study should continue to be treated and followed. The IDMC informed CEL-SCI on December 13, 2016, that because the study was at that time on partial clinical hold imposed by FDA (on 26 September 2016), the IDMC has no formal recommendation regarding continuation of the trial at that time. Another IDMC meeting was held on February 6, 2017. Due to the fact that the study was still on partial clinical hold imposed by the FDA, the IDMC had no formal recommendation regarding continuation of the trial at that time. As noted above on August 14, 2017, CEL-SCI announced that it has received a letter from the FDA stating that the clinical hold that had been imposed on the Company's Phase III cancer study with Multikine has been removed and that all clinical trial activities under this Investigational New Drug application, or IND, may resume. As such, the Phase III study is resuming per the Study Protocol.

Potential treatment in HIV/HPV co-infected patients: CEL-SCI has an ongoing Phase I study of Multikine in HIV/HPV co-infected men and women with peri-anal warts being conducted at the University of California, San Francisco. The purpose of this study is to evaluate the safety and clinical impact of Multikine as a treatment of 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 and its resultant diseases. This group of patients has no viable treatment options available to them and there are, to CEL-SCI's knowledge, no competitors at the current time. HPV is also relevant to the head and neck cancer 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, HPV in a Phase I study of Multikine in HIV 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. 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.