Colorado Gold Rush, Alfredo Rodriguez

INTRODUCTION

On May 27, 2022, CEL-SCI announced the publication of ASCO 2022 abstracts that sketch in vivid color the outlines of the long-awaited full data, which is expected to soon be available on clinicaltrials.gov. 

When I delved into the brief paragraphs jammed full of acronyms and statistical terms which make up the abstracts, I could think of nothing other than “gold mines”: 

• The first gold mine is for Head & Neck cancer patients who could potentially see their tumor disappear after only 3 weeks of non-toxic treatment and extend their lives by so many as four additional years.

• The second gold mine is for investors who, having weathered CEL-SCI’s decades-long up-and-down journey, and the current market storm, survived to potentially thrive as the market eventually comes to the realization that what we are staring at today is a $150m market cap biotech, which is knocking on the doors of the FDA for approval of its Multikine drug with an amazing set of results which should provide a quantum leap in the treatment of solid tumor cancers.

• The third gold mine is the abstracts themselves, with lots of golden information. Allow me to begin drilling for it.

PRE-SELECTION METHOD

Let’s start with the at-first-glance-seemingly-less-significant abstract of the pre-selection method.

As a reminder, Multikine is a neoadjuvant treatment, i.e. it is used before Standard of Care and works well on patients receiving radiotherapy but not chemoradiotherapy. Therefore, it is necessary to develop a method to determine whether a patient should receive radiotherapy or chemoradiotherapy. With such a method in place, Multikine, without hesitation, can be administered to each radiotherapy patient. That being said, given the drug’s safety profile, there should be no significant health problems were Multikine to be accidentally given to a patient subsequently determined to need chemotherapy.

The method explained in the abstract is a filter that separates the low risk from the high risk, in line with the definition used in the Phrase 3 study. As a reminder, in the context of the Phase 3 study, high risk patients are defined as those with: positive surgical margins, 2 or more clinically positive nodes, or extra capsular nodal spread, perineural invasion, etc (any or all of the above).

The method achieves 91.8% accurate predictive value for the low-risk group demonstrating significant overall survival, which is high enough for practical application.

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TUMOR RESPONSE

From the results abstract, the tumor response rate data is summarized in the table below:

Several observations from this data:

• Among 212 patients who received Multikine, with and without CIZ (cyclophosphamide, indomethacin, and Zinc), followed by surgery and radiotherapy (low-risk patients), 34 demonstrated complete or partial tumor response. This represents 16% or 1 in about 6 patients.

• Among 317 patients who received Multikine, with and without CIZ, followed by surgery and chemo-radiotherapy (high-risk patients), or simply dropped out, 11 showed complete or partial tumor response. This represents 3.5% or 1 in about 30 patients.

• Among 394 patients who received Standard of Care only, i.e. surgery followed by either radiotherapy only or concurrent chemoradiotherapy, or simply dropped out, 0 had tumor response.

Several thoughts from these observations:

• Mutikine clearly shows a sizable response rate, 1 in every 6 patients, in the targeted low-risk population.

• Although not explicitly mentioned, there seems to be a complete response (tumor disappearance) for some of the patients, in line with Phase 2 results. This is absolutely mind-blowing given the short treatment period of only 3 weeks. Partial response could simply come from the fact that 3 weeks are too short (yet this is the required treatment protocol of the study) and by extending this 3 week period of treatment, partial response could become complete response.

• Complete response encompasses various terms related to quality of life and hence happiness. Patients could potentially avoid disfiguring surgery, i.e. without having their tongues, cheeks, etc. cut out. 

• Response rate in the targeted population of low-risk patients is nearly 5 times higher compared to high-risk patients. When the results were initially revealed in June of last year, the survival benefit in patients who received chemo-radiotherapy was not so good as for those receiving radiotherapy only. For this reason, chemotherapy was thought not to work well with Multikine. However, this data suggests a potentially different reality that the performance of Multikine might depend on the risk profile of the patients (low / high) rather than on the subsequent treatment (radiotherapy or chemoradiotherapy). High-risk patients have more established cancer tumors which may be harder to successfully attack.

• If the response rate of Multikine depends on the “maturity” of the tumor, then it will certainly be very interesting to use Multikine on patients with cancer stages less advanced than those in the Phase 3 study (Stage III / IVa). This will increase the total addressable market for Multikine.

RESPONSE & DEATH RATES

Not only was the response rate high, but additionally there was also a strong correlation between tumor response and death, as summarized in the table below:

In the targeted population highlighted in red, tumor responders had a 12.5% death rate, or more than 3 times lower compared to the 41.0% death rate from non-responders. In my understanding, this is the first time in cancer treatment history that one can see such a proven strong correlation (very low p-value) between tumor response and death rate. 

This newly proven correlation between tumor response and death rate confirms the robustness of the survival results, making the survival much more tangible, visible (seeing the tumor becoming smaller while, at the same time, knowing that the patient will live longer is absolutely fantastic). It also means a lot for the future of Multikine.

Imagine also how helpful Multikine’s impact on solid tumors in just three weeks could be for CEL-SCI (or its future Big Pharma owner) in terms of returns on investments in a variety of prospective trials for Multikine in other solid tumor cancers! Big Pharma’s record of Phase 3 study failures is not just obviously in front of us, but is significantly littered to our left and right. It is abysmal. Those Pharma studies were like mining for gold without drilling test holes. Now, what if!!!...What if Big Pharma had a three-week test to predetermine the much greater likelihood of a study’s success? CEL-SCI HAS such a test. It is called Multikine!

Through the application of Multikine, when one sees a tumor response, then the Phase 3 study will likely be a success in terms of survival. Otherwise, it will not. This will help CEL-SCI (or its future Big Pharma’s owner) significantly improve its return on investment, allowing quick and inexpensive tests before engaging in an expensive pivotal study.

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SURVIVAL

The abstract reminded us of the overall survival benefits that were disclosed last year, 4.9% at 3 years, 9.5% at 4 years and 14.2% at 5 years. This is an amazing result, showing a durable and increasing survival benefit over time.

Yet the newest piece of information, median overall survival duration is shockingly jaw-dropping : 46.5 MONTHS OR ALMOST 4 YEARS OF ADDITIONAL LIFE FOR TARGETED PATIENTS TAKING MULTIKINE WITHOUT ANY ADDITIONAL TOXICITY.

No one can contest that Keytruda is a BLOCKBUSTER drug, yet its first study results only added a couple of months of additional life along with a RISKY load of toxicity. On a comparable basis, Multikine is 20x better than the best-selling immunotherapy drug in terms of benefit and infinitely better in terms of the lack of side effect risks. Completely amazing!

THE GOLD MINE

“Genius is the gold in the mine; talent is the miner that works and brings it out”. Geert and his team saw genius in the potential of neoadjuvant immunotherapy and their dedicated work and talent is finally “outing” Multikine to the world at large. Nothing is certain in life, but the list of items pointing toward FDA approval is extremely robust:

• Head & Neck represents a severe unmet medical need with no new treatment in about 50 years

• 14% overall survival advantage on an absolute basis and almost 4 years of additional life for targeted patients receiving Multikine

• Sizable tumor response rate and strong correlation between tumor response and survival.

• No toxicity

Now, let’s flip the coin to examine CEL-SCI (CVM) as an investment:

• Sufficient cash until the end of 2023. BLA application and potential approval should happen before.

• $2 billion of potential annual revenues with the current production capacity which can be further expanded.

• Multikine is an extremely flexible platform able to test for other solid tumor cancers, using an innovative approach that allows inexpensive Phase 2 tests before deciding to engage in expensive pivotal studies thanks to the correlation between tumor response and survival.

• Management team who have invested their lives into the business and will do whatever is necessary to bring Multikine to the market.

• On the date of this article, we are speaking about a tiny $150m market cap.

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THE SURVIVAL STORY

CEL-SCI is a story of survival.

MK (Multikine) is poised to help Head & Neck cancer patients survive.

Another MK (this time Mister Kersten) has doggedly kept CEL-SCI afloat and surviving for more than 30 years through all the ups and downs of the market and the drug development process—as well as the slings and arrows which the naysayers have daily seemingly incessantly thrown CEL-SCI’s way.

So perhaps the most successful investors in CEL-SCI will turn out to be those who survive the labyrinth of distracting noise, liars, impatience and fears which lead ultimately to the pot of gold at the end of the proverbial rainbow. (And those who are lucky enough to encounter the story of this company and its drug now).

Good luck to everyone and do not forget to do your own due diligence before investing.