***OFFICIAL CYDY/Leronlimab Thread*** (2 Viewers)

[arrow1]

This stock is maddening 

 

[chet]

 power hour starting

will it be positive or negative?

 

[ChiefD]

 power hour starting

will it be positive or negative?

poo-er hour

 

[Don Hutson]

@YoDoctorYo  · 13h

https://twitter.com/YoDoctorYo 

https://www.washingtonpost.com/health/covid-variant-contagious-spread/2021/01/06/73a1b716-4fc2-11eb-83e3-322644d82356_story.html

Here is something WaPo needs to be more clear about in their reporting.

Monoclonal antibodies that target #COVID19 virus are susceptible to mutations.

Monoclonal antibodies that act as immunomodulators won't be affected by mutations.

 

[Don Hutson]

Most Covid mutations wouldn't affect leronlimab's efficacy.  But the South African Variant of Covid has a mutation that involves binding with CCR5 receptor.  That is also the target of leronlimab.  Seems like efficacy could be affected either positively or negatively.  Any thoughts?

 

[Dave RL]

Medical Layman but I'm pretty sure of the following: LL stops the immune system from going haywire (modulates it) which is the cause of most severe/critical cases of Covid. CCR5 is the signaling pathway that is to root cause of this out of control feedback loop in the immune system. If the virus mutates to spread outside of CCR5 LL will still work as the body will still use CCR5 to signal immune response.

 

[Don Hutson]

@YoDoctorYo  ·  2h  https://twitter.com/YoDoctorYo/status/1347294750953521152

Watch Now: https://www.youtube.com/watch?v=yiveL1kNyCo 

In this video, I am discussing not only when to take medications that can benefit you in COVID 19, but also how- I explain the eIND and expanded use process for RLF 100 and Leronlimab also with all the phases on when to take Ivermectin.

 

[ex-ghost]

Predictions for tomorrow? I say we drop below $5. 

I was technically correct, but meant that we would close under $5. I guess I am happy?

 

[Dwayne Hoover]

I was technically correct, but meant that we would close under $5. I guess I am happy?

I think so, it weathered another storm.

I guess this comes down to whether or not you are planning to get out before the approval or not.  If you plan to stick it out through the approval, then it really doesn't matter what the price is at this point.   If you are looking to sell soon, than definitely a bigger concern.

Just speaking for myself, I unloaded the number of shares I wanted to today, didn't get the best price but I'm happy I did. 

At this point, if it dropped a lot lower in the next couple of days, I'd welcome it and try to get one last trade in because I do think it will drift upward again towards the approval date.

I don't think the above scenario will happen but i wouldn't mind if it did.

 

[ChiefD]

Kind of a pud day so far.

Need a power half-hour to close this week out. 

 

[Dave RL]

Why did Nader Pourhassan and Michael Mulhulland wake up early (or stay up past midnight) to sign the 10-Q? Note that their signatures are dated today (January 8, 2021). Is there a reason they needed it filed PREMARKET on a Friday? Sense something is up. Maybe wanted to forward the 10Q to NASDAQ this morning so NASDAQ could review it today? The timing of the signatures makes me wonder.

Some banter about early 10-Q filing. Interesting

 

[Charlie Harper]

Jam 12 is data unblinding? So we have a week....2 weeks max.  Before this is all over?

 

[Dwayne Hoover]

Jam 12 is data unblinding? So we have a week....2 weeks max.  Before this is all over?

Yeah and just counting the deaths from each arm would be quick.  Regardless of having all the data analyzed and ready for presentation they should know if they beat placebo on deaths right away.  There will be a period where the hospitals have to certify the data and I don't know how long that is but beyond that the primary endpoint should be clear.  

 

[Dwayne Hoover]

Looks like the death rate for standard of care in the tocilzumab and sarilumab trials was around 36%

https://www.nytimes.com/2021/01/08/health/covid-arthritis-drugs-reduced-deaths.html

The findings in a new paper show that treatment regimens involving the drugs tocilizumab or sarilumab reduced the death rate among Covid patients in intensive care to about 27 percent, compared with 36 percent among patients who did not receive the drugs. Based on these results, about one death would be prevented for every 12 I.C.U. patients treated early with these drugs. All of the patients in the trial received the drugs within 24 hours of entering intensive care.

https://www.medrxiv.org/content/10.1101/2021.01.07.21249390v1

 

[Chaz McNulty]

Looks like the death rate for standard of care in the tocilzumab and sarilumab trials was around 36%

https://www.nytimes.com/2021/01/08/health/covid-arthritis-drugs-reduced-deaths.html

The findings in a new paper show that treatment regimens involving the drugs tocilizumab or sarilumab reduced the death rate among Covid patients in intensive care to about 27 percent, compared with 36 percent among patients who did not receive the drugs. Based on these results, about one death would be prevented for every 12 I.C.U. patients treated early with these drugs. All of the patients in the trial received the drugs within 24 hours of entering intensive care.

https://www.medrxiv.org/content/10.1101/2021.01.07.21249390v1

If the SoC is anywhere close to 36% in the CD12 trial, then this stock absolutely moons.

 

[Dwayne Hoover]

While it does introduce more competitors for leronlimab if those drugs are approved, they may have a very short window when they can be administered.  It looks like they may have found a sweet spot of showing benefit when being given those drugs on the first day of a patient being admitted to intensive care.  

 

[Don Hutson]

Does "intensive care" include both severe and critical?

 

[Dwayne Hoover]

If the SoC is anywhere close to 36% in the CD12 trial, then this stock absolutely moons.

It should be noted that all of the patients in those trials were in the intensive care unit so death rate would be higher

 

[Dwayne Hoover]

Does "intensive care" include both severe and critical?

Yeah, I don't believe severe is in intensive care, at least not all.  Trying to verify that but that's my understanding.

 

[BassNBrew]

If the SoC is anywhere close to 36% in the CD12 trial, then this stock absolutely moons.

If that happens and the LL arm has fewer deaths than the placebo arm @chet will be a very rich man. If this stock can get to the Nasdaq.first it would be awesome 

 

[Charlie Harper]

Does "intensive care" include both severe and critical?

I believe severe critical are patients requiring supplement oxygen only. This was a huge disconnect for me as a health care provider. 

 

[Chaz McNulty]

If that happens and the LL arm has fewer deaths than the placebo arm @chet will be a very rich man. If this stock can get to the Nasdaq.first it would be awesome 

I'm optimistic because management cannot get in the way of the trial results.  Science will speak when they unblind the data.  It either works or it doesn't.  At this point I really like the odds of them hitting their primary endpoint.

 

[Don Hutson]

I believe severe critical are patients requiring supplement oxygen only. This was a huge disconnect for me as a health care provider. 

I'm still confused.  Are you saying that severe is bad, critical is really bad, and intensive care is really, really bad?

 

[Charlie Harper]

Here's from the CD12 clinical trail description...

A. Severe Illness:

- Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing within 5 days of screening

AND

Symptoms of severe systemic illness/infection with COVID-19:

- At least 1 of the following: fever, cough, sore throat, malaise, headache, muscle pain, shortness of breath at rest or with exertion, confusion, or symptoms of severe lower respiratory symptoms including dyspnea at rest or respiratory distress

AND

Clinical signs indicative of severe systemic illness/infection with COVID-19, with at least 1 of the following:

- RR ≥ 30, HR ≥ 125, SaO2 <93% on room air or requires > 2L oxygen by NC in order maintain SaO2 ≥93%, PaO2/FiO2 <300

AND

- None of the following: Respiratory failure (defined by endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure in setting of resource limitations), Septic shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg), Multiple organ dysfunction/failure

So "severe" is just your typical med-surg level patient. Basically anyone requiring hospitalization. Critical is what what you would traditionally see in the ICU.

ETA: That's why the mild-moderate was a dumb study..it was basically people that didn't need hospitalization. Also, why there's promise if it positively impacted such mild cases.

 

[Chaz McNulty]

I'm still confused.  Are you saying that severe is bad, critical is really bad, and intensive care is really, really bad?

From my limited understanding, most of critical would be in ICU, and some of severe would be in ICU.

 

[Charlie Harper]

From my limited understanding, most of critical would be in ICU, and some of severe would be in ICU.

All of severe would just be regular medsurg level patients. Even some of critical "high flow oxygen" could be handled on med-surg level. 

CD10 was basically non-hospitalized. CD12 is basically all hospitalized patients. 

To be fair this is roughly the same definition the remdesivir trials used.

 

[Don Hutson]

I think I remember from the interim analysis that two-thirds of leronlimab's S/C trial are severe and one-third are critical.  If true and 36% of the placebo critical patients in leronlimab's study passed, then it would take 12% of the placebo severe patients to pass to get the overall placebo mortality rate of 28%.  A 28% overall placebo mortality rate with a 19% treatment mortality rate is what many believe is the minimum that leronlimab needs to be considered for an EUA.  

 

[Dwayne Hoover]

 then it would take 12% of the placebo severe patients to pass to get the overall placebo mortality rate of 28%.

This seems possible, but perhaps a little higher than you would expect.  We are in close to toss up territory if true.

IDK overall here, I'm definitely not as confident as others that they are going to have statistical significance.  May trim more.

 

[Don Hutson]

It's going to be interesting what the final mortality number ends up being.  It's likely going to be higher than 87.  As that number goes higher, leronlimab's prospects for statistical significance go lower.

 

[jamny]

So Tuesday is the make or break day? Before or after market?

 

[Dwayne Hoover]

So Tuesday is the make or break day? Before or after market?

Hospitals have to sign off on results.  Deaths have to at least be analyzed to get the correct cause of death.  I don't think it will be Tuesday.

I'd guess we should know the following week on the primary endpoint. 

 

[chet]

Hospitals have to sign off on results.  Deaths have to at least be analyzed to get the correct cause of death.  I don't think it will be Tuesday.

I'd guess we should know the following week on the primary endpoint. 

I doubt it will be the following week.  Thinking week of Jan 25.

Also, CYDY needs to realize that there's a PR game to be played here.  Regardless of p-value, BP would be all over the media if the trial results in lower mortality.  Those are valuable headlines.

 

[Dwayne Hoover]

I doubt it will be the following week.  Thinking week of Jan 25.

Also, CYDY needs to realize that there's a PR game to be played here.  Regardless of p-value, BP would be all over the media if the trial results in lower mortality.  Those are valuable headlines.

edit again as I can't read the calendar.

I think we should hear something between the 18th and 22nd at least on primary.  If news is good, I have a hard time believing NP can hold his cards that long.

If it drifts into the week you are talking about, Ill be getting more concerned they didn't hit primary.

 

[Capella]

I doubt it will be the following week.  Thinking week of Jan 25.

Also, CYDY needs to realize that there's a PR game to be played here.  Regardless of p-value, BP would be all over the media if the trial results in lower mortality.  Those are valuable headlines.

No doubt. Considering the garbage PR they usually put out, if they skip this it’s another dramatic error. 

 

[Dave RL]

Where did we get the 1/12 date for the unblinding from? I thought the PR was on the 12/21 so wouldn't that be the 16th (+28 days)? 

 

[Dwayne Hoover]

Where did we get the 1/12 date for the unblinding from? I thought the PR was on the 12/21 so wouldn't that be the 16th (+28 days)? 

The PR was the 15th and I don't think it's even clear that it was the actual date, perhaps could have been a day or two earlier even

 

[Don Hutson]

Where did we get the 1/12 date for the unblinding from? I thought the PR was on the 12/21 so wouldn't that be the 16th (+28 days)? 

There doesn't seem to be any verification of the 1/12 date.  It is solely based on adding 28 days onto the pr that said the trial was completely enrolled.  That pr didn't say when it became completely enrolled so it could have happened a few days earlier.  It also didn't say that all enrollees had gotten their first shot.  The 28 day clock doesn't start until the last enrollee gets their first shot.  So the clock could start a few days after 1/12.

 

[BassNBrew]

I doubt it will be the following week.  Thinking week of Jan 25.

Also, CYDY needs to realize that there's a PR game to be played here.  Regardless of p-value, BP would be all over the media if the trial results in lower mortality.  Those are valuable headlines.

Cool. Can’t wait to see the spinning globe and breaking news music. 

 

[Don Hutson]

If the FDA doesn't grant an EUA but instead asks for the trial to enroll another 393 patients, will we find out the results of the first 393 patients?  I'm going to be really frustrated if I don't find out the mortality rates of the treatment and placebo arms.  I don't own one share of CYDY.  But I want results divulged!

 

[Chaz McNulty]

If the FDA doesn't grant an EUA but instead asks for the trial to enroll another 393 patients, will we find out the results of the first 393 patients?  I'm going to be really frustrated if I don't find out the mortality rates of the treatment and placebo arms.  I don't own one share of CYDY.  But I want results divulged!

I believe Cytodyn will have the results at this point.  The only reason not to release them would be if they were really bad.  Your scenario above would have the same affect on stock price as a phase 3 fail.

 

[Dwayne Hoover]

If the FDA doesn't grant an EUA but instead asks for the trial to enroll another 393 patients, will we find out the results of the first 393 patients?  I'm going to be really frustrated if I don't find out the mortality rates of the treatment and placebo arms.  I don't own one share of CYDY.  But I want results divulged!

Doesn't NP have a bunch of other countries lined up?  To be honest, I have no idea if he really does but he would have to publicly unblind results to sell to other countries.

If we don't see results here, I'd say it's DOA

 

[Dwayne Hoover]

I believe Cytodyn will have the results at this point.  The only reason not to release them would be if they were really bad.  Your scenario above would have the same affect on stock price as a phase 3 fail.

Agree with this

 

[Dwayne Hoover]

In the event they don't meet the requirement initially, wonder what would happen if they do better with the critical group than with the severe.

Would FDA give any credibility to that?

At this point I do have my doubts but it's an interesting question.

 

[Charlie Harper]

Take it for what it's worth given the source (I haven't went and actually looked at the studies), but here's some info on mortality: tweet 1 | tweet 2. Just presenting info to be considered, not trying to make anyone grumpy - no position at this point.  

My personal stance here is I will forever be grateful to @chet for the call here, made a bunch of loot - but I have come to believe, in general, management matters. I also believe mortality as the primary endpoint makes this tough and maybe not great risk/reward going in to unblinding. If the data isn't great with the company is already valued at ~$3.5 billion dollars there is a lot of room to fall. I think we can get lost in the stock price sometimes and forget what it extrapolates to. For example, $HGEN has an $850M market cap a 4x difference (and I believe a generally higher chance of getting approval given how the studies have been setup. See: importance of management). 

I went back and using the 18% mortality rate from this tweet we get 23 control deaths and 64 LL deaths and we get a p-value of 0.156. So obviously the shorts picked studies that wouldn't meet statistical significance.

37/130 in placebo is 28%.

50/260 in LL is 19%.

I think this gets us to statistical significance.  I didn't calculate this, but just repeating what I heard.

I get just barely over at p value of 0.053.

I used THIS calculator for both values. So if 87 is the final death number we have to hope the control group mortality is at 30% vs 18%. Also any extra deaths likely decreases the chances of LL having statistical significance. 

Definitely looks like a slim window.

 

[Don Hutson]

Definitely looks like a slim window.

It's a slim window but it's a window that could work.  A result of 28% placebo/19% treatment would be phenomenal.  And it works with the numbers we have been given.  Also, a 26% placebo/20% treatment, 24% placebo/21% treatment, and a 22% placebo/22% treatment all work with the numbers we have, too.

 

[Charlie Harper]

It's a slim window but it's a window that could work.  A result of 28% placebo/19% treatment would be phenomenal.  And it works with the numbers we have been given.  Also, a 26% placebo/20% treatment, 24% placebo/21% treatment, and a 22% placebo/22% treatment all work with the numbers we have, too.

The calculator I was using showed that 28% is just barely above the 0.05 level of significance. Does 0.1 level get FDA approval?

 

[Don Hutson]

I think it's 393 patients.  And the number of deaths is the sort of thing Nader would lie about.  He knows that more than 87 deaths starts seriously limiting leronlimab's chances at statistical significance.  He can just claim that he didn't know about some of the most recent deaths.  The study finishing with 90-95 deaths wouldn't be surprising.  And the study being 393 patients could push back the Jan 12th date since the pr could have been released when the 390th patient was enrolled, not when the 393rd patient was enrolled.  The 28 day clock starts when the last patient gets their first shot.

 

[chet]

I went back and using the 18% mortality rate from this tweet we get 23 control deaths and 64 LL deaths and we get a p-value of 0.156. So obviously the shorts picked studies that wouldn't meet statistical significance.

I get just barely over at p value of 0.053.

I used THIS calculator for both values. So if 87 is the final death number we have to hope the control group mortality is at 30% vs 18%. Also any extra deaths likely decreases the chances of LL having statistical significance. 

Definitely looks like a slim window.

Assuming your calc is correct (i used the Wolfram calc to get a p-value of .0236 for similar numbers), this is what BP would use as a marketing opportunity. CD12 results in a significant reduction in mortality but the result is not quite statistically significant.  There's nothing competing in this slot and the world would benefit from leronlimab being approved.  

Personally, I see two outcomes as being overwhelmingly more likely than others:  

1) CD12 shows leronlimab sig reduces mortality in a statistically sig way; and 

2) CD12 show leronlimab sig reduces mortality but p-value is above .05.  

I know the drug works but is NP capable of designing a trial to showcase the drug's capability.

 

[chet]

I went back and using the 18% mortality rate from this tweet we get 23 control deaths and 64 LL deaths and we get a p-value of 0.156. So obviously the shorts picked studies that wouldn't meet statistical significance.

I get just barely over at p value of 0.053.

I used THIS calculator for both values. So if 87 is the final death number we have to hope the control group mortality is at 30% vs 18%. Also any extra deaths likely decreases the chances of LL having statistical significance. 

Definitely looks like a slim window.

I don't know why your site produces such a different number than the Wolfram calculator.  Anyone qualified to explain?

 

[BassNBrew]

Assuming your calc is correct (i used the Wolfram calc to get a p-value of .0236 for similar numbers), this is what BP would use as a marketing opportunity. CD12 results in a significant reduction in mortality but the result is not quite statistically significant.  There's nothing competing in this slot and the world would benefit from leronlimab being approved.  

Personally, I see two outcomes as being overwhelmingly more likely than others:  

1) CD12 shows leronlimab sig reduces mortality in a statistically sig way; and 

2) CD12 show leronlimab sig reduces mortality but p-value is above .05.  

I know the drug works but is NP capable of designing a trial to showcase the drug's capability.

Can you please elaborate on why you know the drug works?