VIENNA, Va.--(BUSINESS WIRE)--The following letter was sent by CEL-SCI Corporation (NYSE American: CVM) to its shareholders for the upcoming annual meeting:
Dear CEL-SCI Shareholders:
The enrollment of 928 patients in our Phase 3 clinical trial of Advanced Primary (just diagnosed and not yet treated) Head and Neck Cancer was completed in September of 2016. For the study to end we have to wait for 298 events (deaths) in the two main groups to show a survival benefit. Based on published survival data, we had already expected to have reached the 298 events. Instead, we had to extend the contracts with the Clinical Research Companies (CROs) running the Phase 3 study because we had not yet reached the required number of events in the study. While we do not like waiting, we also recognize that this may be a positive development for our Phase 3 study since Multikine may be the reason for not yet having reached 298 events. Let us explain to you why.
The primary objective of our Phase 3 study is to demonstrate that, by administering the Multikine treatment regimen prior to the current standard of care therapy (SOC), surgery followed by radiotherapy or followed by combined radiochemotherapy, we can achieve a 10% increase in overall survival of the Multikine treated head and neck cancer patients. In a much smaller uncontrolled Phase 2 study Multikine appeared to increase overall survival even more. If Multikine does increase overall survival in our well controlled Phase 3 study by 10%, it will likely take longer to reach 298 events.
Our ultimate goal is to show that Multikine, when given before surgery, radiation and chemotherapy have weakened the immune system, improves the cancer patients’ survival and confers clinical benefit. Should we be successful in reaching this goal, we hope to extend the use of Multikine to treat other cancers and maybe even other diseases.
Think of family and/or friends who have undergone cancer treatments. Usually the first treatments consist of surgery, radiation and chemotherapy, or any combination thereof. If these treatments “cured” the patient, the issue was resolved. However, if there is a recurrence of the tumor, more treatments follow, and the outcome is generally not good. Life may be extended for only a short time, with many horrible side effects along the way.
The most common misconception with respect to the use of Multikine is that it is in competition with all of the recently FDA approved immunotherapies (e.g., Keytruda, Opdivo, CAR-T) that have been in the news. However those treatments are NOT in competition with Multikine because they are not intended for use in the same head and neck cancer patient population we are targeting for Multikine. Multikine is given to advanced primary head and neck cancer patients who are newly diagnosed, before they receive their first SOC treatment, which is surgery. These other immunotherapies are indicated only for patients whose cancers have recurred following SOC, those patients with metastatic cancer, and patients where surgery is not an option.
Multikine is given in combination with SOC treatments that are called “intent to cure” because doctors expect that these first cancer treatments will cure a certain percentage of patients. Surgery, the first component of SOC, is usually performed within 3-4 weeks of diagnosis. A delay in an “intent to cure” SOC treatment is not permitted because that delay may lead to a patient’s death sooner than if treatment had not been delayed. Multikine also is not allowed to delay the surgery, hence Multikine is administered for only 3 weeks prior to surgery. The use of the previously mentioned cancer immunotherapies (e.g., Keytruda, Opdivo, CAR-T) in the same patient population being treated with Multikine would be both inappropriate and unethical because they are administered over many months, which would cause a delay in surgery. Further, the toxicities that may be associated with these other cancer immunotherapies may also preclude their use in patients who are potentially curable by the current SOC.
We chose to explore advanced primary head and neck cancer as a lead indication for Multikine for the following reasons:
- Advanced primary head and neck cancer makes up about 2/3 of the 650,000 head and neck cancer patients per year.
- On average, about half of these patients will die within 3 years; and there is only one standard of care for this disease.
- The last FDA approval for this indication was about 60 years ago. These patients have a clear unmet medical need.
If we are successful in significantly improving the overall survival for these patients, we will have made a great advance in the treatment of this cancer. However, as noted, we believe that Multikine may be a useful agent to add to therapies currently used to treat other cancers too.
Years ago, when we started developing Multikine cancer immunotherapy, the scientific community did not believe that the immune system could ever be used to fight cancer. Even when we initiated our Phase 3 clinical trial, the attitude was still very critical of cancer immunotherapy. Today cancer immunotherapy is thought to be the future of successful cancer treatments. Our premise all along was that the immune system is incredibly powerful. It needs to be activated in the right way to fight cancer before it is destroyed by surgery, radiation and/or chemotherapy. We believe we found a way to do so with the Multikine treatment regimen. That is the basic belief that guides us every day.
Our Phase 3 study in head and neck cancer has taken eight years. Throughout all of these years, due to the study design of the Phase 3 clinical trial, we had no clinical data to report while the trial was ongoing. That is akin to an eight year drought. However, we are now finally at the end of the study and investors are becoming interested again. Our valuation was a mere $20 million when we sent you a shareholder letter in July 2018. Now, in March 2019, it is approximately $90 million. We had many millions of dollars in warrant exercises providing the company over $12 million of cash in the past 10 months. We have a clean balance sheet with no debt. Several large and well known funds have returned to our stock. New investors in the US, Canada, and Europe are taking positions. We are on the right path. Of course, our success rests on the Phase 3 clinical trial data.
In the past 2 years, several successful Phase 3 cancer companies were sold for multi-billion dollars, most of them before FDA approval, and a few right afterwards. The most recent acquisition was by Eli Lilly who bought Loxo Oncology for about $8 billion. The key to that kind of a valuation lies in providing clinical benefit to cancer patients. Remember, the last FDA approval in this cancer was well over 50 years ago and, as far as we know, Multikine is the only drug being evaluated for use in treating advanced primary head and neck cancer.
In summary, we want to give you the details of when patients were enrolled and the survival assumptions for the SOC group in our Phase 3 study:
- Approximately 135 patients were enrolled in the study from 2011 to 2013, about 195 were enrolled in 2014, about 340 in 2015, and about 260 in 2016
- The last patient was enrolled in the study in September 2016
- The study protocol assumes an overall survival rate of about 55% at 3 (three) years for the SOC treatment group alone, but obviously the event rate in patients who have been in the study longer than 3 years will be higher
Some people have wondered if somehow the SOC treatment for advanced primary head and neck cancer has become more successful in increasing the overall survival of these patients during our eight year clinical trial. We have seen no evidence of this, and do not believe this to be the case. A recent scientific article on essentially the same patient population as treated in our Phase 3 study, during almost the same time as our Phase 3 study (European Journal of Otolaryngology (2017) 274:2567-2572 https://slideheaven.com/treatment-outcome-of-advance-staged-oral-cavity-cancer-concurrent-chemoradiother.html), appears to confirm our belief. The survival curves in this publication do not look different to us than did the survival curves from the published studies we used to design our Phase 3 clinical trial.
We have managed to undertake a massive cancer study of eight years, a huge feat for a small company. We have reached the point where we will soon have data that could prove our concept for an improved way of treating newly diagnosed cancer. We continue to believe that we will be successful.
Chief Executive Officer
This shareholder letter contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. When used in this press release, the words "intends," "believes," "anticipated," "plans" and "expects," and similar expressions, are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Factors that could cause or contribute to such differences include, an inability to duplicate the clinical results demonstrated in clinical studies, timely development of any potential products that can be shown to be safe and effective, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital and the risk factors set forth from time to time in CEL-SCI’s filings with the Securities and Exchange Commission, including but not limited to its report on Form 10-K for the year ended September 30, 2018. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.
* Multikine (Leukocyte Interleukin, Injection) is the trademark that CEL-SCI has registered for this investigational therapy, and this proprietary name is subject to FDA review in connection with the Company's 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 involving the investigational therapy Multikine. Further research is required, and early-phase clinical trial results must be confirmed in the Phase 3 clinical trial of this investigational therapy that is in progress.