Biotech

CytoDyn’s Smoking Gun For an Immediate EUA

The controversy surrounding CytoDyn Inc. (OTCMKTS: CYDY) stock is startling.  An aggressive pack of  short sellers claim its leronlimab Covid trial…

The controversy surrounding CytoDyn Inc. (OTCMKTS: CYDY) stock is startling.  An aggressive pack of  short sellers claim its leronlimab Covid trial  didn’t meet endpoints while  a devoted group of investors insist that the drug works better than any therapeutic and has the data to prove it.  To this group, many of them doctors and scientists, there is no controversy and they have begun a letter writing campaign to sharpen the FDA’s attention onto the drug. The good news is you can see what the FDA sees in the data below. Leronlimab works for Covid-19. 

Clinical trial data can be summarized in one “odds ratio” chart showing   a drug’s performance relative to a trial’s primary and secondary endpoints.  Leronlimab works relative to placebo and it works better than any approved therapeutic. Physicians understand the ramifications of the data in this chart. The data proves that leronlimab works better than anything you are currently allowed to take for Covid-19. 

“My interpretation of the CD-12 study is simply that in the critically ill population in a well balanced age group the outcome and absolute risk reduction is phenomenally better than any other medication that we have in active use either as an EIND or an EUA in our institution. The benefit that we saw in the critically ill population translates into absolute risk reduction much more than what Dexamethasone has shown, which has been used liberally all over the world.” – Dr. Hareesh Seethramraju – Montefiore Medical Center    

Investor Call Update

One of the major highlights of the call was CytoDyn’s announcement that they formally filed for a conditional EUA 10 days ago. A conditional EUA means that dosing would be tied to a specific patient population like elderly critically ill.  Chairman of CytoDyn, Scott Kelly believes they have a “clear path forward and working very closely with regulatory agencies throughout the world” and that they are in the top 5% of studies that have been randomized and adequately powered. He also pointed out that the UK variant represents 30% of infections in the United States which means that the virus is here to stay and leronlimab has a role because it is not affected by the variants emerging.  The 24% reduction in mortality in the critical population represents the best results in the world. The CD10 trial with age adjusted data had statistically significant sub-populations that the Company hopes the FDA will consider for a conditional EUA. 

They are preparing for a CD16 for critical COVID-19 patients under 65 with an endpoint of time to recovery.  In a separate request for CD17 they are asking to start with an IV and then move to 2 more shots in the over 65 year old group.    

Revenue Opportunities

  • Conditional EUA from the FDA
  • MHRA – March 4th – Permission to file for Accelerated Rolling Review – It will be granted
  • Europe EMA – Preparing a request to meet – Fast approval with EMA
  • Health Canada – Submitted timeline which is first section of Interim Order (IO)
  • Philippines – Looking for 5-10 Compassionate Special Permit (CSP) Case for EUA is stronger
  • Brazil – Identifying a marketing holder to move forward – Meeting request with ANVISA (Brazil FDA)
  • Hungary – Talking to Minister of Health – sending presentation and Executive summary

*** Should any of these opportunities close then NASDAQ uplisting is expected. 

The Open Label Extension arm is doing very well.  They commented that the OLE is looking better than their CD12 results but only 6 people in the trial were critica.  Health Canada will be the first HIV BLA to be submitted provided they don’t ask for a receptor occupancy test.  They are scheduling a meeting with the FDA to discuss Breakthrough Therapy Designation (BTD) in a basket trial of cancer.  The NASH trial is enrolling well and they expect it to be completed this year.  The Long Hauler trial enrolled 36 of 50 patients and is expected to read out in 6 – 8 weeks.  The pathogenesis of Long Haulers is neuroinflammation from cytokines that works its way through the blood brain barrier.  

Reading an Odds Ratio Chart

The Odds Ratio (OR) is essentially the probability that something is happening over the probability that something is happening in a different group. In the CD12 clinical trial CytoDyn measured the probability of death using leronlimab over the probability of death not using leronlimab.  

A couple of quick examples will get investors up to speed quickly.  The baseline in almost any study is that the drug does nothing which means the death rate between the two groups isn’t going to differ. The probability of death will remain the same in either group.  In this scenario the odds ratio is 1.0 and there is a 50% chance of death in either group.  Notice what happens if the drug is harmful then the probability of death increases. In this example of 80% mortality, which was realistic early in the pandemic, the numbers exaggerated the effect so it’s obvious what a harmful therapy looks like.  This will be helpful when remdesivir is evaluated on the plot later on.  Typically what you want to see is a much lower death rate over the standard of care which translates into an odds ratio less than 1.0  when it comes to the mortality rate.

A good rule of thumb is:   

  • OR >1 indicates the drug isn’t working
  • OR <1 indicates the drug appear to be working

A forest plot is a graphical way to show what the odds ratio is for that particular group or subgroup of patients.  In the chart below the orange dot is a plot of the odds ratio value for the particular drug and patient group which is also highlighted in orange text for effect.  The line attached to the dot stretches horizontally in both directions.  This is the confidence interval.  In small studies the confidence interval tends to be very wide and in larger studies with many patients the confidence interval has a tendency to contract.  The confidence interval also predicts that if a study was repeated the trial data would be expected to fall within that band of outcomes.  So the more area of that band that is on the less than 1.0 side of the chart the better the study.

It is very simple to decipher the chart below, the lower the odds ratio with respect to mortality the better the treatment. When testing for a specific variable then successful outcomes are on the greater than 1.0 side of the study.  They are clearly labeled so just be careful to read the outcomes on both sides of the plot.   

These charts clearly show that Leronlimab is better compared to the Placebo arm.  There is additional detail that also shows that the leronlimab and dexamethasone combination is better than dexamethasone alone.  This also makes sense because leronlimab quiets the cytokine storm by hitting a number of chemokines and dexamethasone compounds the effect.  In critically ill patients the effect of leronlimab was even more pronounced.    

The analysis gets very interesting when dexamethasone is compared to tocilizumab and remedesivir.  On the chart there doesn’t appear to be much variability and dexamethasone and tocilizumab look about the same, but that is very deceiving because it’s on a logarithmic scale. The effect of tocilizumab is not as pronounced as dexamethasone yet it was approved for an EUA.  For analysts and doctors that understand how to read clinical trial results and this forest plot remdesevir is clearly the drug that doesn’t belong.  Yet is it approved while leronlimab waits its turn.  The orange dot is sitting in the over one category which means that the placebo is better than remdesivir.  At first glance that might not make intuitive sense how the FDA approved a drug that not only doesn’t work that well, but is more dangerous.  Keep in mind the timing of the approval was done early in the pandemic when a marginal drug was better than no drug at all.  .    

CD10 Mild to Moderate Study Showed Statistical Significance

In the CD10 trial of mild to moderate COVID-19 patients completed in August 2020 one of the endpoints in the trial was the incidence of hospitalization.  Leronlimab reduced the incidence of hospitalization in this group.  The hospitalization rate in the standard of care was 10.71% versus 1.79% for leronlimab.  This was statistically significant on the whole group and it was demonstrated that the drug didn’t work on the mild cases which represented 50% of the leronlimab treated patients.  It reasons that there could be an even greater reduction if this was applied to moderate patients. 

The trend over the next 6 months indicates that this is becoming more of a young person’s disease.  In this age group it’s just as important to prevent hospitalization as it is in preventing death in the nursing home population.   

Investment Summary

Leronlimab is the best in class drug for COVID-19 but US taxpayers are bearing the brunt of all this money that is being funneled by Operation Warp Speed (OWS) toward big pharma for marginally useful drugs and vaccines that are susceptible to variants. This has created an atmosphere where the FDA has been prioritizing vaccines over treatments.  Leronlimab definitely meets the FDA’s “may be effective” definition, but they are in the queue behind big pharma.  Once the FDA digests the data it could be just a matter of time before it is approved.  The FDA hasn’t said “no” to an EUA so investors need to really think about using this opportunity to buy discounted shares before the inevitable “yes.”  It is also the only drug that seems to benefit COVID-19 patients across the entire spectrum of the disease from moderate through critical.  There are no reported severe side effects from clinical studies and the CD10 study concluded it was less safe to do nothing than take the drug.  Dr. Lalezari has been doing clinical trials for 30 years and he has never seen a result where taking the drug had less side effects than doing nothing.  

The company presented 6 statistically significant endpoints that demonstrate the drugs worth.  The forest plot of leronlimab could be the poster child of any approvable drug. When looking at that plot side by side the already approved dexamethasone, it’s impossible to see how the FDA could deny something so obvious. This chart is the smoking gun of a drug that works and no FDA commissioner is going to want to testify why it took so much time in a pandemic to approve a drug that was so unquestionably obvious.  The shorts paint a different picture, when it’s daytime they want you to believe it’s night.  They want you to believe that even though it may work, the p-value is more important to the FDA.  Don’t let them fool you.        

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Disclosure: Insider Financial and its owners do not have a position in the stocks posted and have posted this article for free without editorial input. This article was written by a guest contributor and solely reflects his opinions.

CytoDyn’s Smoking Gun For an Immediate EUA
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