CVM; A Win for Medicine, a Death Sentence for Cancer and shorts

2021年7月6日

DISCLAIMER
I am financially invested in this stock, I have 4200 shares, and a considerable amount of calls for an unspecified date and amount. So yes, I, in a very big way, am selling you. I financially benefit if you, the investigative reader, buy CVM shares or, very possibly, calls. That means that this is not financial advice, this is a sales pitch, so if you don't think you can separate pitch from information, avoid this article. I have been apprehensive on writing this article as I accept my bias, and while I will present the following analysis of the study results, and possible implications, I am extremely biased and my ability to make a rational decision could 100% be compromised. What I present is my best explanation of the trial results, what I believe to be occurring to the price, and some of the scenarios Multikine could play out.

Now that we have gotten through that; This is in no way, shape or form, fluid and function, an analytical, qualitative or intelligent compte rendu. There is absolutely no financial advice here because the only financial advice I can give is to research, research, and research. The purpose of this analysis is to serve as an example of an investigation into a company's background, fundamentals, and assets through various lenses to determine if it is a good potential investment for you. The function of this write up is to serve as an educational resource for investors looking to understand how to find good investments. So read and learn some things about a company that cured cancer, yeah, the big C.

Thesis -Clinical Analysis
businesswire.com/news/home/20210628005472/en/CEL-SCI’s-Multikine®-Immunotherapy-Produces-Significant-14.1-5-Year-Survival-Benefit-62.7-Vs-48.6-in-the-Group-Receiving-Surgery-Plus-Radiotherapy-in-a-Landmark-Head-and-Neck-Cancer-Phase-3-Study

I made this very basic figure: twitter.com/NucleotideSoup/status/1411192599080321024

Big question is which treatment would you ask for?

The hard line is a 14% increased 5 year survival in Head and Neck cancer patients with a solid tumour being treated with Multikine as opposed to the current standard of care(SOC). All without a single safety issue, meaning it wasn't making patients sick, and as it was given 3 weeks before surgery and radiation, there was plenty of time for the immune system to go into hyperdrive mode and present serious issues.

I know I write a metric $#%@ ton of words, but y'all, I try and always let the data do the work. This is as pretty as it gets in my shoes. At the end of the day, there are no sub-statistics that matter, because in every single patient population that got Multikine, there was an increase in survival. CIZ is a weird little multivitamin that has been found to boost a ton of drugs' effects in the clinic for completely unknown reasons, or at least they were unknown last time I checked, but it is more designed than developed, but it legitimately does some incredible things. My hypothesis is that the mix helps reduce oxidative stress, which isn't a major issue for normal people walking around, which is why it is never found to have an effect on its own in any clinical setting, but it does seem to help in these various trials. This is a little too scientific, but oxidative stress is turning out to be the number one pathway in disease and just general cellular maintenance. I actively work on this scientifically, so there is a lot of contentious hypothesizing, but I am finding that oxidative stress would have been a relatively simple evolutionary step to take early on in macro-cellular organisms, but humans have done everything except. One of the major issues that is rarely thought of in a scientific lab setting is the oxidative stress of the environment caused by the massive amount of cellular death from therapeutic death of cancer cells. Sometimes killing the cancer too fast can overload the bodies ability to dispose of the dead cells, and cause major systemic issues and death. Yeah, sometimes killing cancer can just kill the patient because they are too weak to handle getting rid of all the dead tissue in them. No, this is not an easy task, but damn if we don’t keep trying. Also oxidative stress and inflammation are very linked!

Cisplatin is a toxic drug, meaning it is bad for you. The only reason you take it is if there is something worse for you that it might kill first. This is one of those situations where my background as a biochemist and cancer research gives me a leg up on the average investor, I have personally used cisplatin in experiments on primary human cells testing cancer-genesis with various DNA damaging agents. While I can't give those results to you, I can summarize it as yeah Cisplatin is pretty freaking awful, and it should only ever be used if there is nothing else.

Enter the reasoning for going after Head and Neck cancer; 6% of all cancer diagnoses per year (meaning big bucks) + no new treatment approved in over 2 decades + orphan drug designation from FDA making it a little easier to file the paperwork. This point needs to be emphasized hard here, there is nothing unique to head and neck cancer that makes Multikine be specific to it. CVM don't intend on applying for FDA approval for a small subset of Head and Neck cancer patients and biting the bullet on a smaller population pool. CVM are going after FDA approval for that small pool with immediate open label use. I will testify before a court of law, I would formally request Multikine as treatment if I were diagnosed with cancer tomorrow. I am very, very, very excited for Multikine to get to the clinic, this is the game changer that we have been waiting for and it is killing me that we are not celebrating this one. Fuck the stock price, can we get a round of fucking beers for a god damn cure for cancer.

This is the only important line from the release:
In addition, as the OS results for the lower risk of recurrence patients (no chemotherapy) are significant (two-sided p=0.0236, HR=0.68) and the effect is robust, durable and increasing over time, CEL-SCI plans to seek FDA approval for Multikine cancer immunotherapy in this underserved patient population.

• OS
  -overall survival- overall survival benefit being increased percent of people who survived from Multikine- percent more living people thanks to Multikine
  
• lower risk of recurrence patient
  - patients with a tumour grade of Head and Neck cancer deemed to be low risk of metastasis and coming back post-therapy
  
• significant two-sided p=0.0236
  -essentially boils down to could only happen by chance once in 42.4 times, meaning the difference in survival in the Multikine population is in fact, not simple chance, but actual clinical correlation/causation.
  
• HR=.68
  -HR means Hazard Ratio, is a direct ratio of probably of death. A HR of .68 means that for every singular patient who dies from the Surgery+Radiation arm, only .68 people die from the Multikine+Surgery+Radiation arm. Lower the HR, better the outcome
  
• The effect is robust, durable and increasing over time
  -I wouldn't know what that meant without them explaining that the overall survival advantage increases past 5 years. Where cured of cancer is defined as 5 years without remittance, Multikine is curing cancer. Of course this is hearsay until we see the statistic results ourselves, but I would hesitate doubting a company that could be crushed if they didn't back that up with real numbers.
  
  
  Now, the bigger picture of the trial:
  twitter.com/NucleotideSoup/status/1411199220065964033
  
  To put it bluntly, Multikine and Cisplatin don't work well together. As of right now, we have no idea if Cisplatin + Multikine has an overall survival 5 year rate of 9.5%, or an overall survival 5 year rate of -100%. My personal theory is that Cisplatin is going to destroy any effect that Multikine had on the system. Multikine is injected into the primary and secondary tumour sites 3 weeks pre-surgery followed by cisplatin and radiation or just radiation. Multikine has 3 weeks to do its job before surgery comes in, followed by radiation and Cisplatin. If Multikine didn't complete its job in 3 weeks 100%, as in there was any considerable amount of cancerous tissue remaining, Cisplatin is going to come in and do it's job, like it or not.
  
  Cisplatin is like Chris Farley in a Little Coat to those tumour cells. To the few that manage to survive and make the EMT transition, or if the cancer stem cells survived (if those are even real, my guess is that this is a pool of cancer cells with an extremely fluid transcription profile that are kind of going back and forth between EMT-MET), cisplatin is ripping through their genome like a coffee bean grinder. I thought long and hard about the appropriate level of destruction I have seen from chromosomal spreads of cells on cisplatin, and coffee grinder feels pretty damn close sometimes. Cisplatin works by sticking to parts of the DNA in multiple places, making it impossible for the cell to make an exact replica of its genome, thus inducing mutations that could lead to death. Cisplatin causes more damage in quicker dividing cells; Cisplatin causes DNA damage, DNA damage that will be ignored and lead to fatal mitotic chromosomal splits/rearrangements, or DNA damage that will be addressed and fixed by healthy cells unless it is too great in which case they will choose to die rather than risk becoming cancerous later on.
  
  Turns out some cells are just more selfish than others, they don't want to die. Cisplatin cancer reoccurrence is a very real thing that has been suppressed for a long time for a laundry list of reasons, namely being doctors and clinical scientists genuinely don't believe the patient is intelligent or informed enough to decide their own treatment course. That is putting it harshly, but essentially, Cisplatin was approved a long time ago and there are millions of people who have gotten millions of collective years on this planet thanks to Cisplatin. However, we are at the point where serious clinical work is being dragged down by Cisplatin because of the need to put every patient on it that can be on it regardless of theoretical alternatives. That and fighting with the FDA is pointless, they can just walk away and tell you go screw yourself. If CVM had any intention of having an arm from the get go of the total patient pool being only Multikine + Surgery + Radiation, I am 100% positive that 5 minutes talking with the most monotonous man in an off-white shirt with a terrible chemical structure tie, an FDA badge on a lanyard around their neck, sitting across from them as they awkwardly pull out their Worlds Best Federal Inspector of Medicine mug that they fill with their thermos with the Pfizer and AstraZeneca logo on it in the SHAPE OF A PILL, didn't just suck their will to live, he most certainly told them that every single cancer patient that can get the current SOC, will get SOC.
  
  There is 1 silver lining element here that I would love to actually see datamined out (yes this is what datamining is); patients were not screened for fully functioning immune systems, meaning there were patients that could have been removed from the trial that were not as the drug would have had no way to cause a significant clinical effect. And that is where the real question begins with the Cisplatin + Multikine data. Was it because Cisplatin destroyed the immune system, thus stunting any long term immune response from Multikine, or is Multikine and Cisplatin not compatible on a more complex mechanistic teeter?
  
  youtu.be/b4qV4pXkp0g?t=69
  
  This is where I suggest CVM already knew Multikine wasn't going to work with Cisplatin. The way the trial was set up from the beginning illustrates they knew Cisplatin was never going to play nice.
  
  
  I would like to point to Keytruda's first phase 3 results, and their FDA clearance history:
  ncbi.nlm.nih.gov/pmc/articles/PMC5137544/
  Hint: Keytruda doesn't cure anyone. It just gives you more time, which is absolutely incredible and should not be taken from anyone. But it isn't a cure, it is a part of the cure.
  drugs.com/history/keytruda.html
  June 30, 2014 - Keytruda is under regulatory review
  September 4, 2014 - Keytruda is approved by the FDA
  
  Keytruda gave people a few more months to live and it did it safely, without severe adverse effects. Keytruda was approved in 2 months.
  
  Dispelling some of the fake newslines
  The major reason this has taken over 30 years: [B][I]THERE IS NO PRECLINICAL TEST TO TELL IF THIS THERAPY WORKS ASIDE FROM NON HUMAN PRIMAPES[/B][/I]
  It is invariably going to be tag line for short hedgefunds to stress "if it is so good, then why did it take 30+ years to get here". Unfortunately, the answer is the system. The system sucks, and the system has led to countless deaths because they are incredibly corrupt, inept and archaic. I am gifted by an interesting career in biotechs. I also have an interesting history in the financial markets. Part of this gives me insight into the crippling corruption in the CRO system, all the way to the approval system of the FDA, where countless lawsuits have proven correct that, yes, the FDA does accept bribes. CRO's are corrupt and disgusting monster corporations, anyone interested in a storied one could look no further than Parexel, which was getting bogged down with so many lawsuits and allegations that they had been abusing their position and purposefully not enrolling patients in small-scale biotech's clinical trials so their drugs never got through the long trials. There has been a number of interesting academic papers that have come out looking at the success/failure rate of drugs through clinical trials, and how prior to ~2012 something like 99% of drugs came out of large scale pharmaceutical companies. Unfortunately, as these papers are academic and the authors lacks a fundamental understanding and history of the system governing the clinical trial system, they fail to point out how many of these large scale pharmaceutical companies bribe CRO's, bribe the FDA, and work to spin extremely negative news in these clinical trials. Literally, these scumbags have gotten a hold of clinical study trial participant lists and called them all and fucking with the system by making them think they were going to die if they got the drug.
  
  Want a sample study, look not further than our very own CVM: businesswire.com/news/home/20180627005364/en/Cel-Sci-Wins-Breach-of-Contract-Ruling-against-Clinical-Research-Organization-inVentiv-Now-Known-as-Syneos-Health
  
  There are no pre-clinical assays, especially not 30 years ago, that could give you the effects of a working immune system on a tumour. Mice do not have working immune systems, nor is there a guarantee any of the components in Multikine retain their appropriate pathway responses in any other species aside from humans. The major issue with a lot of diseases, like Alzheimer's, is the lack of a suitable test for drugs to know if they have an effect or not. It is not practical to screen drugs in patients (also not ethical), but the system has made it even more difficult to take drugs that work in human specific pre-clinical assays but do not have a suitable animal model to get into clinical trials. This has gotten better, but only very, very recently as the FDA has been slowly getting changed by a new wave of scientists and more-forward thinking government employees. Part of that leads us to the latest fiasco where an Alzheimer's drug without a clinical effect gets approved and cost ~60k per year, which no way any nationally subsidized health insurance is going to pay. Part of that leads us to the countless fiascos of the countless drugs that have fallen through the cracks due to the system.
  
  Fortunately, here we are, in 2021, with clinical trial results in hand and a much less suitable drug given the royal treatment as a role model.
  
  cel-sci.com/wp-content/uploads/2020/06/Scientific_Multikine_Presentation_061020.pdf -page 6 for Head and neck cancer reasoning -pg 8 also good read
  bloomberg.com/press-releases/2019-10-24/cel-sci-corporation-issues-letter-to-shareholders -good discussion of Keytruda in this shareholders letter
  
  Summary of Phase 3 FDA Trial
  Multikine cures cancer in a specific subset of Head and Neck patients who did not get Cisplatin, which destroys the immune system, thus negating the effects of the drug.
  Multikine had no negative medical events, meaning it was completely safe for EVERY SINGLE PATIENT WHO GOT IT.
  Multikine activates the immune system against the tumour, similar to the way a vaccine allows your immune system to hunt down a virus or bacteria extra-well, but in a much more advanced way.
  
  
  Theoretical Medical Relevancy
  CVM's Multikine gets the immune system going red hot against solid tumours, but there is no study or data on how it would behave against a metastasized secondary tumour site, or against a metastatic cancer in general. I would not be surprised if Multikine is used in every single cancer given the patient has a working immune system. Furthermore, if Multikine is found to be safe in repeating doses, I can see maintenance Multikine being a serious clinical strategy.
  Furthermore, CVM has preclinical studies going on Multikine in COVID infection, likely investigating more chronic viral infections as well. If Multikine is able to blanket activate the immune system, causing it to be super thorough, there is no reason not to consider it in any and every single infection scenario, viral and bacterial. I absolutely can see Guillain-Barre syndrome in a much broader population study, or other various auto-immune system issues, but part of me wants to say that this can be removed with dosages, and part of me is curious if the multi-pronged interleukin pathway activation from Multikine doesn't offer some sort of critical auto-immune system inhibitor. This is a completely novel therapy, and the immune system *typically* tries not to destroy its host. An interesting read on guillain-barre here (pubmed.ncbi.nlm.nih.gov/31074417/) shows that some anti-interleukin 17 agents are possible treatments for this, meaning if negative side effects do happen, the fact that the alternative is cancer killing the patient, it is doubtful this hinders the drug, and that medically therapeutic options exist. Truthfully, most GBS events and auto-immune events are scary but transient. Interestingly, the interleukin pathway is crazy, and really still not fully known. Some of the interleukins inhibit each others pathways, some of these in very specific ways to modify the effects. This is just going to be one of the things that has to pop up in large scale clinical trials, especially as Multikine is tested in countless other therapies where the native immune system can be leveraged to do its job (i.e. every single infection).
  
  Multikine getting FDA approval is absolute, to what scope is less so. Multikine will get open label use for cancer, but whether any research hospital chooses to bend that for study in other biologically relevant illnesses is another. With the Immune system being the flavour of the decade, I can only imagine how deep clinicians reach in for this one. Theoretically, Multikine would be effective in wounds, especially gunshot/knife wounds where there is a clear point of entry for infection. Multikine could be used as an emergency treatment used as an adjuvant therapy while the patient is stabilizing and wound closed. I am scientifically and medically excited for the uses of this drug.
  
  Personally, I would love to see liver cancer treatment with Multikine, specifically liver because liver exosomes are particularly easy to purify from Urine, meaning you could monitor biomarkers routinely through the treatment effect, given they were present in urine exosomes of course. It is a little unethical and cruel to do, but getting some tumour samples would be amazing during the treatment as well. Ideally, Multikine is activating the immune system in the tumour region where the immune system is gathering epitopes against the mutated proteins on the tumour, or to simplify it a little, the tumour starts looking foreign to the immune system as it makes errors here and there and "new" proteins. These are hypothesized to be present and if the immune system could be activated against these, they would be able to hunt down the tumour cells at the primary site, but would be primed against any re-establishment of the tumour should a cancer stem cell survive or a metastasized colony is present elsewhere, the immune system should now be able to hunt them down and kill them everywhere. It would be very cool if we could take the immune system population from a patient treated with Multikine, and see if they are specifically targeting that patient's tumour versus other primary tumour samples.
  
  Thesis - Price Action/Manipulation Strategythc-lab.net/stock.html
  This article is absolutely worth while in reading. I am sorry that this is the way the world works, I truly am. I believe that we are close to real change, but I think it's more thanks to Bitcoin than anyone wants to admit.
  
  Looking at the short ratio reported day in, June 28th the short volume is monstrous, the way it is 50-50 makes me think this is a bunch of phantom shorts that were sold short before borrowed, with a hypothesis that the resurgent volume spike on the 30th might have been short hedgefunds recycling their shorts on the T+2 cycle. The fact they haven't yet from the June 30th intrigues me greatly, could be they found the way to bury them matched call:puts as there was a massive spike in far out of the money puts and options on the second half of the week. Alternatively, we could see a volume increase on a T+3 cycle, as is common in those looking to take the longest time to cover their previous short sales, willing to take a small fine if they get one on abusing the T+2 date, but still way ahead of the T+6 antics of Penson Financial(now Apex), and still even way more ahead of the T+21/T+35 FTD cycles that we can see repeating in the volume spikes (and congruent price spikes) over the past few months since the initial impulse to 40. Either way, should be a fun week.
  nakedshortreport.com/company/CVMThesis- Price Target and Discovery
  Fact, M&A's are red hot right now. Also Fact, the markets are really wonky right now. There is no guarantee on a blockbuster acquisition being possible even if the drug really is all that, just because the banks don't know how to stop being greedy. However, you cannot take the value out of a drug that cures cancer, so while an M&A could take a while to precipitate, the price action should reflect the massive increase in value of CVM, especially given the way the market has been valuing M&A targets previously such as QuantumScape, Tilray/Aphria, and countless others (wow the M&A market really has been red hot).
  
  I have hit some intrinsic form of word limit, so I will keep it short. I see a short term market capitalization anywhere from the $1.5-3 billion range, where we could see extreme impulse ranges in the $10-30 billion market capitalization (the short squeeze trend has made these massive volatility channels outrageously hard to predict but fantastically enjoyable as a long). Truthfully, I could see an M&A deal panning out extremely quickly in the $5-10 billion range should a company rush quick while CVM is still learning to count 0's, but I would rather them take the time to get the full value where we could see the biotech records being broken, because again, this drug cures cancers.
  
  TA is nuts to do right now just because the rules got changed so hard, and the way the price is so obviously being manipulated with the rhythmic ladder attacks and buybacks and the insane drops timed with margin shuffles. I wouldn't try and read the lines too much here, looking to hop in and out of channels as they come and go. Set a price target, set a loss limit, always do your research.
  
  Check out pharmaintelligence.informa.com/~/media/informa-shop-window/pharma/2020/files/whitepapers/ma-whitepaper.pdfDisclaimer
  Thank you for reading this analysis. The sole purpose of these are to serve as an educational resource for any one to gain an understanding of what to research when deciding to make an investment. If there is any material in this analysis that you feel could be explained better, or in more detail, or even if you have just a little question, let me know! As I develop this skill, my aim is to expand the reach of these articles to cover more topics to a wider audience. Feedback helps me grow, so I am happy to read the comments.
  
  For legal and ethical reasons, this is not financial advice, I really really really cannot stress that enough. Furthermore, I do own 4200 shares at an average price of $14 per share. This information is given due to European financial regulations, not as financial guidance. This information is only accurate as of the date of publication, July 6th, 2021. The original, and only version published by me is on Tradingview.com.