Cel Sci Corporation (CVM)

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ON THE MARKET: CEL-SCI Marches Ahead with New European Patent on Its Multikine Cancer Immunotherapy

Dr. John L. Faessel

ON THE MARKET

Commentary and Insights


CEL-SCI is granted a new European Patent on its Phase 3 Investigational Cancer Immunotherapy Multikine


CEL-SCI Corporation (CVM) NYSE MKT

It is high time to explore the science of CEL-SCI in somewhat more depth, now that the company has been granted a new European patent* on its Phase 3 investigational cancer immunotherapy Multikine


The press release relating to this new European patent cites as “important” a reference to Multikine’s mechanism of action, whereby the drug changes the type of T cells that enter the tumor microenvironment. This change results in the tumor becoming "visible" to the immune system, resulting in a robust and sustainable anti-tumor immune response.The ‘visible’ aspect is critical because cancer cells have the ability to ‘hide’. This ‘exposure’ of cancer cells has been the focus of the new assault on cancer in which an assortment of new drugs has proved to be successful on some cancers—a boon to the companies involved and resulting in huge market-cap appreciations.

The new patent describes a method for altering the CD4 / CD8 T cell ratio and the mononuclear cellular infiltrate into a tumor. The ratio of CD4 cells to CD8 cells is a measure of immune function, telling the clinician how balanced and strong one’s immune system is.

The crucial and decisive feature of Multikine’s action covered by the patent

About 200 patients were treated with Multikine before the final Phase 2 data presented here: In Phase II trials Multikine circumvented the tumor defense mechanisms and induced a reversal of the CD4/CD8 ratio in the tumor infiltrating cells, leading to a marked increase of CD4 T cells in the tumor. This resulted in the prolongation of the anti-tumor immune response and tumor cell destruction.

Exceptional and positive results with Multikine in clinical studies confirmed by pathology have been published in the Journal of Clinical Oncology[JCO]. The net upshot is that Multikine achieved a 33% improvement in survival over standard care at 3.5 years post-treatment in the Phase II trial. In addition, CVM’s anticancer immunotherapy increased the overall survival to 63.2% at 3.5 years from treatment. (See detail in some depth below** regarding the clinical studies.)

Noteworthy specific results mentioned in the JCO article (link here)

Following only 3 weeks of treatment in two of 19 Multikine-treated patients (patients 5 and 14; Table 1), it was not possible to detect any cancer tissue in the surgically resected tumor mass, and thus, these patients were considered to be complete responders (exhibiting 100% tumor reduction by histopathology as a result of Multikine treatment regimen).

In two other Multikine-treated patients (patients 7 and 18; Table 1), the imaging technique verified more than 50% tumor volume reduction, which was considered a partial (major) response (two of 19 patients); and in four LI-treated patients (patients 4, 6, 9, and 12; Table 1), the volume reduction was proven to be more than 30%, which was considered a minor response (four of 19 patients). Progressive disease (≥ 40% tumor volume increase) occurred in only one patient (patient 17), whereas stable disease was detected in the rest of the patients (10 of 19 patients).

This data is in line with earlier studies where Multikine was given for 2 or 3 weeks.In each case some patients had a complete tumor elimination and some a partial tumor elimination.Considering that the primary goal of this very short treatment before surgery is to clean the margins of the tumor and thereby reduce the risk of tumor recurrence, the complete elimination of a tumor is surely a positive sign.One would think that this type of benefit should translate into a survival benefit and that is why CEL-SCI is conducting the global Phase 3 trial.

Briefly about the company

CEL-SCI Corporation is an advanced stage immunotherapy company with aplatform of technologies that can potentially treat a variety of cancers and viral diseases. The company is well into Phase III trials for the treatment of head and neck cancer. 608 patients are now enrolled in the Phase III study with 38 patients, a new high for a single month, enrolled in October. By mid-2016 a total of approximately 880 patients are expected to be enrolled through about 100 clinical centers, to date; the study is ongoing in 24 countries. It’s the largest Phase III study for the treatment of head and neck cancers in the world.

About head and neck cancer

Worldwide there are an estimated 600,000 new cases of head and neck cancer diagnosed each year, which represents about 5-6% of all newly diagnosed cancers. The five-year survival rate is around 30%, a rate that has not materially improved across decades. Overall the death rate from all cancers combined is in a continuing decline that began in the early 1990s. Notably though, head and neck cancer is one of those segments that has seen little improvement over the last several decades where the outlook for those that suffer is generally quite grim and its denouement particularly gruesome with survival rates for these patients beyond disheartening. There’s a huge potential market of $6 billion for CEL-SCI’s Multikine treatment if FDA approval comes. Moreover, the combination drug immunotherapy could have numerous other applications going forward, bringing new hope to the afflicted.

About Multikine and its raison d'être

CEL-SCI’s Multikine investigational therapy is comprised of a defined mixture of (cell-free) cytokines. It is not one cell or one protein, but rather a combination of molecules and proteins—interleukins, interferons, chemokines, and colony stimulating factors derived from the stimulation in culture of normal immune system cells. Atypically, even uniquely, Multikine is given before conventional cancer therapy is undertaken—that is, before the body’s immune system is hugely depleted and weakened after enduring chemo-and radiation therapy, and thus at a point when the immune system may be more robust. Hence the idea, which became the fundamental insight and CEL-SCI’s raison d'être: working with and supporting the body’s own immune system before it is compromised by the downside of today’s standard of care for cancer (surgery, radiotherapy, chemotherapy, or a combination of these treatment modalities).

So again, tantalizingly, what CEL-SCI has accomplished is to duplicate the body’s mixture of cytokines derived from the stimulation in culture of normal immune system cells and produce a ‘combination’ therapy that, in theory, simulates the natural immune system and boosts the body’s own anti-tumor immune response. Further, and more importantly, Multikine is intended to help kill the micro-metastases thought to be responsible for cancer recurrence, and thereby increase survival.

As I mentioned above, the current treatment modalities are varied and numerous, but this actually applies only to the end stage patient. These days, if you are newly diagnosed with cancer you basically have just three options: surgery, radiation and chemotherapy. That’s no change in the 50+ years in the evolution of cancer treatment.

So, what’s remarkable and truly astonishing about Multikine is that the company developing this science believes that it has created a 4th treatment modality—immunotherapy delivered at the site of the primary tumor. No other company but CEL-SCI is pursuing this novel approach, as all other cancer immunotherapy is directed at recurrent cancer in patients. This is the specific revolutionary thrust of the CEL-SCI research and treatment construct. CEL-SCI hopes to use its focused immunotherapy to increase the “cure rate” and to potentially eliminate, or at least drastically reduce, the untoward and dreadful treatment modalities currently in use as the standard of care.

Slightly off-topic but relevant as a comparable treatment evolution

Consider how HIV/AIDS just a few years ago was looked at as a disease with a 100% dire prognosis. A single drug, zidovudine, was discovered that seemed to help those afflicted. Then, after a massive input of research, a combination therapy (i.e. a “cocktail” of drugs) was advanced in an accelerated FDA category to treat the disease to the point where the HIV antibody doesn’t show in blood tests at all (as long as the drug combination is taken by the patient in a very disciplined regimen). Gilead Sciences (GILD) Nasdaq developed one of those HIV cocktails and the shares of the company went from $0.27 to now over $106, with a market-cap of now $153 billion and sales of over $31 billion a year. Such is the reward—or “golden ring”—at the successful end of treating a condition once considered “untreatable” whose afflicted, to put it bluntly, were doomed.

Similarly, the hepatitis C combination therapy is thought to cure 96% of those patients who did not already have cirrhosis or liver cancer. Key players are AbbVie (ABBV) NYSE – (market-cap of $99 billion with sales of over $21 billion) and Gilead Sciences (GILD), here again at the forefront. Hepatitis C is another terrible condition that now is treatable with a combination therapy.

More on Multikine

Preliminary data derived after successful Phase I and Phase II trials and near 60% of the way thru Phase III trials suggest that Multikine has the potential to:

· act on multiple receptors on the cancer cells

· act on multiple components of the immune response, and on the tumor cells themselves

· activate immune pathways known to be necessary for addressing the tumor

Early-phase data suggests that Multikine potentially shows combination immunotherapy activity: that is, it may have the potential to simultaneously present both active and passive properties to act against cancer cells (see Timar et al., Laryngoscope 2003and Journal of Clinical Oncology 2005). If confirmed, the research would suggest that the combined activity of Multikine could closely resemble the activity imparted by a healthy person's immune system, which can monitor for and take action against cancer cells.

Multikine has been developed to be injected percutaneously, i.e. via needle-puncture of the skin, with one half the dose delivered peritumorally (around the tumor) and the other half dose administered perilymphatically (injected in the region of the local/regional draining lymph nodes).

Phase III study end point

For the Multikine arm in the current trial, a 10% (or better) advantage in overall survival over standard of care interventions by themselves is the basis for demonstrating efficacy and establishing the use of Multikine as a first-line therapy.

** Further detail from theJournal of Clinical Oncology


Clinical trials using Multikine in over 200 patients have been completed in Phase II with the following results: link herefor the Journal of Clinical Oncology ** [JCO]abstract that reported on the findings. In brief:

1) so far it appears to be free of any major toxicities.

2) It has been shown to render cancer cells much more susceptible to radiation therapy.

3) The Journal of Clinical Oncology publication revealed the following:

(i) Multikine induced anti-tumor immune responses through the combined activity of the different cytokines present in Multikine following local administration of the therapy for only three weeks.

(ii) The combination of the different cytokines caused the induction, recruitment into the tumor bed, and proliferation of anti-tumor T cells and other anti-tumor inflammatory cells, leading to a massive anti-tumor immune response.

(iii) Multikine induced a reversal of the CD4/CD8 ratio in the tumor infiltrating cells, leading to a marked increase of CD4 T cells in the tumor, which resulted in the prolongation of the anti-tumor immune response and tumor cell destruction.

(iv) The anti-tumor immune-mediated processes continued long after the administration of Multikine was halted.

(v) A three-week Multikine treatment of patients with advanced primary oral squamous cell carcinoma resulted in an overall response rate of 42% prior to standard therapy, with 12% of the patients having a complete response.

(vi) A histopathology study showed that the tumor load in Multikine-treated patients was reduced by nearly 50% as compared to tumors from control patients in the same pathology study.

(vii) The tumors of all of the patients who responded to Multikine treatment in this Phase II trial were devoid of the cell surface marker for HLA Class II. This finding, if confirmed in the presently ongoing global Phase III clinical trial, may lead to the establishment of a marker for selecting the patient population best suited for treatment with Multikine.

An aside

For those who may not know how tissue samples / biopsies are handled in a straightforward and honest fashion, here is a quick briefing on how they were treated in the study that was the subject of JCO abstract cited above.


The histologic evaluation of each patient's tumor section was performed by three independent pathologists (J.T., C.F.-H., and B.D.), and, in case of disagreement, consensual determinations were reached. Morphometric measurements were performed by the same three pathologists without knowledge of the clinical background and treatment outcome of each of the patients.

The upshot

Immunotherapy / immune-system enhancement is on the cutting edge of cancer research and treatment today. This is validated by the staggering $197+ billion of funding that has come into the biotech industry over the last two years as estimated by the Burrill Report, much of it directed at immune system enhancement. CEL-SCI’s solid success in Phase I and Phase II trials, and its creditable progress in the Phase III study, suggest not just potential but better than a good chance of FDA approval in Phase III, in my opinion.

Contemplate the exceptional value, based on CEL-SCI’s low market capitalization of around $61 million versus other immunotherapy cancer / immune-oncology [I-O] related companies where market caps are in the hundreds of millions and billions. For the first time ever, cancer is on the run. And with the truly exceptional highpoints listed above, CEL-SCI is in the center immunotherapy treatment mix with a good chance of Phase III success where mind-blowing dollar amounts for such success are the order of the day. CEL-SCI / (CVM) is indeed a stock to own or at the very least have on your screen and follow.

* The new European patent, # EP 1 753 452 B, is entitled: A METHOD FOR ALTERING THE CD4/CD8 RATIO AND THE MONONUCLEAR CELLULAR INFILTRATE INTO A TUMOR.

I have bought shares and warrants of CEL-SCI on the on the open market and it is my intention to buy additional shares.

For further information, please see (CVM)’s comprehensive web site: www.cel-sci.com

Investment risks

·CEL-SCI is far along in its Phase III trial, although to date it does not yet have a product approved for marketing.

·There is the inherent risk associated with all micro-cap biotech companies of the need for additional dilutive financings to fund operations.

·The cost of conducting this Phase III clinical trial and the time required to meet regulatory approval could take additional years.

·CEL-SCI may need to raise additional capital to fund these trials.

·CEL-SCI may not prevail in the upcoming arbitration and there may not be a settlement.

·CEL-SCI’s outcome as company is heavily dependent on the results of its large Phase III trial.

·CEL-SCI has other indications in early stage trials, unfavorable data in the Phase III trial could be damaging to the company.

·A new class of immune-therapies is meeting with success in clinical trials. Yet, should one of these immune-based therapies not succeed, it may cast a negative shadow on all, or similar, immune technologies, in the eyes of regulators including the FDA.

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