First, this isn’t advice. At all. Just my own re
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Posted On: 05/28/2020 3:19:15 PM
First, this isn’t advice. At all. Just my own research and opinion. It is undoubtedly flawed. So take it with a grain of salt.
So in light of how close we are (on the scale of weeks) to seeing a conclusion to Covid as an indication for Leronlimab, I decided to focus my efforts on understanding the playing field we currently find ourselves on. With HCQ and REM, the two most public touted drugs now out of the running, it’s anybody’s game more or less.
I wanted to know what the competition was like, where they stood in terms of timing, efficacy etc. So I referenced a post on another board ( https://www.racap.com/med…/Covid-19/COVID-1...0_F.pdf… ) which was an infographic that charted all current Covid 19 treatments that are underway. After having found some that were not listed on that graphic, the total came to 51 different treatments (including Leronlimab).
For each of the 50 other treatments I wanted to 3 things specifically –
1) Will they announce topline results before us?
2) Are they safer than us?
3) Are they more effective than us?
So I went to googled and began researching each treatment, one by one since yesterday. I’ll provide a numeric breakdown of what I found then I’ll get into more qualitative analysis, particularly more on the treatments that are actual threats. I referenced company PRs, clinical trial sites and third party news reports to answer these questions.
Total Candidates – 51
Total Candidates Eliminated – 38
Eliminated due to timing – 30/38
This category contains treatments that for one reason or another would pose no threat to Leronlimab in terms of announcing topline data/ finishing trials before us. Treatments in this category possessed characteristics such as “trial initiated 05/26/2020”, or “treatment still in development” or “large enrollment size, but only 1 clinic enrolling,” etc, etc.
Eliminated due to Preliminary inefficacy – 2/38
This category contains treatments that failed to produce efficacy with result thus far. An example of this would be Avigan, which was recently rejected by the health minister of Japan for showing no clear benefit.
Definitively eliminated by institutions – 2/38
This contains treatments such as REM and HCQ that have been publicly acknowledged as ineffective or incomplete by major journals or institutions.
Eliminated due to controversy or association – 2/38
This contains PRED, which after doing a quick google search you can see that it debated whether or not it will be effective. Also contains a structural analog of chlorquine.
Eliminated Due to study design – 1/38
Single arm study.
Eliminated due to safety – 1/38
This includes a treatment (plivensia) which was rejected by the FDA for a RA indication.
Now to move on to the treatments that I felt represented a legitimate threat to CYDY in terms of when the companies would be able to announce topline/interim results or were a threat based on comparable efficacy.
It is of note that the immediate numbers below represent what the PRIMARY threat each treatments represents is. Multiple treatments were threatening with respect to timing and also had demonstrated some efficacy.
Total Candidates Threatening – 10
Threatening with timing of topline results – 9/10
This particular group was comprised almost entirely antibody-based therapeutics that targeted some aspect of the cytokine storm. 4 of these treatments had some form of anecdotal evidence to suggest that they would be efficacious in treating covid patients. Knowing what we know about the respiratory disease Covid causes, we can be sure that this is the case and that for the patients who have not progressed into full blown immunological disease that these treatments will be of benefit to them. 5 of these treatments had major side effects. Among the worst were Kevzara, Ruxolitinib and Actemra. Additionally, convalescent plasma is in this group and given what we know about plasma viremia from Dr. P’s pre-print there is a high likelihood that this will be an issue with donor units.
This group represents treatments that will most likely present therapeutic value to patients and have a chance of reporting topline results before or around the same time as Cydy.
Threatening with efficacy of treatment – 1/10
This group only had one treatment and it is a stem cell based therapy by MesoBlast. Their anecdotal evidence is reminiscent of Leronlimab’s with respect to stunning efficacy on the sickest patients. One caveat is they either have not treated or published the data regarding the use of their treatment on additional EIND patients. This treatment does not represent a threat in terms of timing. Their expected completion date of trial is in 3-4 months per their recent earnings report. Another issue is scaling, they recently raised (I think 90M$) to build a manufacturing facility. This to me means they will not be ready before CYDY to meet demand.
Important caveat is this company has stated it plans to release interim data when they reach 100 patients. They began enrolling 5.6.20.
2 Treatments there was not enough data for me to form an opinion.
The 51st treatment is Leronlimab.
Ok the rest of this will be my perspective / opinion on the situation.
Doing this much research has given me a different perspective on things. Let me start by saying I’ve visited other message boards for a few of these treatments and it is eerie how the exact same issues get discussed. Every other board has the same concerns as us. They have their bashers they deal with. They have paranoid thoughts and suspicions regarding the motives of the FDA. Again, it is eerie. But that helped me understand that fear manifests itself in similar patterns across all humans across all investments and that my focus should be on the science and timing / positioning of the company.
What I’ve also seen is that literally no other company is as transparent as Cytodyn is with regards to sharing patient outcomes in the EINDs. It’s really amazing. We’re very lucky that NP shares as much as he does. If we’re to believe that the best drug wins, then it’s obvious to me that we posses the best drug and that we are at least very competitive among the others.
Now, the overall situation we find ourselves seems to be the following –
CYDY leadership will have to decide within the next couple of weeks whether or not they wish to unblind the trial, perform analysis and submit to the FDA. This is based on enrollment speed. There’s 2 ways this
________PURE SPECULATION AT THIS POINT______
Scenario 1) enrollment picks up and trials complete enrollment by 3rd-4th week of June, TOPLINE results out by end of 2nd week/3rd week of July.
RISKS: In my opinion the primary risk associated with this course of action is that there most likely will be a handful of other trials that will release topline data before us or near us and we will lose any momentum associated with the media coverage that comes along with being the first.
PROS: Even though we would most likely lose that “first to report” momentum, it will be to a treatment that will be not nearly as effective as Leronlimab. And it will likely be to a treatment that is targeting critical/severe patients while our indication is mild/moderate. We would have the statistical strength of 75 patients and would not run the risk of the FDA asking for additional data since they designed the trial.
Scenario 2) enrollment stalls over the next two weeks, they unblind the study and submit TOPLINE results by 3rd or 4th week of June.
RISKs: The risk associated with early unblinding is losing the statistical strength associated with the full enrollment and not completely fulfilling the parameters of the FDA’s trial design.
PROS: IF our results were absolutely over the moon off the charts stunning, it would be hard for the FDA to demand more info given the safety profile of Leronlimab.
In either case, how do we know Leronlimab will be effective for mild/moderate patients?
First, we know it is effective with just the absolute worst of the worst. So it’s logical to assume that it would be effective on m2m. Beyond assumption, it’s clear that Dr. P’s paper correlates the administration of Leron to it’s MOAs that then support the clinical outcomes we were seeing with the patients that were “on death’s door.”
But to take it one step further and analyze a recent study and perhaps extrapolate efficacy of Leron, I look at this.
https://www.ncbi.nlm.nih.gov/…/a…/PMC7177...bl0002/…
This is a study where Baricinitib (a JAK inhibitor whose function is to reduce or reverse lung inflammation) was administered to patients already on ritonavir-lopinavir (repurposed protease inhibitor) and respiratory parameters were measure at 1 and 2 weeks compared against a Standard therapy only group (NOT EVEN PLACEBO;ritonavir-lopnavir).
After two weeks what they observed were statistically significant improvements in the following in the Baricinitib group OVER the SOC group. AGAIN this is being compared against a SOC group, NOT a placebo group. A placebo group would’ve done even worse and that statistical significance would’ve increased for these and other parameters:
Cough
Dyspnea
Fever
Sp02
Pa2/Fi02
CRP
MEWS Discharge %
Now if you refer to our M2M study you’ll see that the primary outcome measures are
myalgia
dyspnea
cough
for fever
Now if you reference Dr. P’s pre-print you’ll see that there is a clear reduction in IL-6 and viral load. Dr. P has also mentioned that other inflammatory markers decreased and that they’ll most likely be included in follow up papers. Rantes is one such marker I’m sure will show up in graph displays in future papers.
So here’s my point with referencing this other study.
The study, though not placebo controlled, showed that Baricinitib which only posses one MOA was able to cause statistically significant improvements in M2M patients over those using SOC in THE SAME parameters that our study is measuring. So knowing what we know about Leron’s MOAs (decrease Cytokine Storm, restore immune balance, reduce viral load), is it likely that Leron will also cause statistically significant improvements in M2M patients in the same parameters?
Yes.
Whichever path they choose with regards to either unblinding early or waiting for enrollment, I’m very confident that we will see statistically significant improvements over PLACEBO in the parameters they’ve outlined. That is not a concern to me.
Conclusion
We are literal weeks away from a conclusion. It will get turbulent, have no doubt about that. Shorts know that TOPLINE results are not too far off. You will see SP suppression, lies, etc. coming out left and right. I guarantee other message boards will show the same thing over the next few weeks.
My perspective is that Leronlimab, out of 50 other treatments is the only CCR5 blocker. It is the only treatment with multiple MOAs that address each aspect of Covid. It has a well proven safety profile.
In my opinion, if we wait for trial enrollment (so long as it is moving forward) that is our best option. The worst consequence of this course of action is we share the limelight with 2 -3 other antibodies that are one dimensional in their approach to treating covid.
The only other most effective treatment is unlikely to beat us to the punch, and even if they did, they are still building their manufacturing facilities and won't scale like we can.
Odd balance right? Those that beat us to TOPLINE aren't as effective OR safe. The treatment that is AS effective and AS safe as us, won't beat us to the punch.
After evaluating the competition, my conclusion is that Leronlimab is STILL in a class of its own.
Hold tight everyone.
ONLY IMO!!!
So in light of how close we are (on the scale of weeks) to seeing a conclusion to Covid as an indication for Leronlimab, I decided to focus my efforts on understanding the playing field we currently find ourselves on. With HCQ and REM, the two most public touted drugs now out of the running, it’s anybody’s game more or less.
I wanted to know what the competition was like, where they stood in terms of timing, efficacy etc. So I referenced a post on another board ( https://www.racap.com/med…/Covid-19/COVID-1...0_F.pdf… ) which was an infographic that charted all current Covid 19 treatments that are underway. After having found some that were not listed on that graphic, the total came to 51 different treatments (including Leronlimab).
For each of the 50 other treatments I wanted to 3 things specifically –
1) Will they announce topline results before us?
2) Are they safer than us?
3) Are they more effective than us?
So I went to googled and began researching each treatment, one by one since yesterday. I’ll provide a numeric breakdown of what I found then I’ll get into more qualitative analysis, particularly more on the treatments that are actual threats. I referenced company PRs, clinical trial sites and third party news reports to answer these questions.
Total Candidates – 51
Total Candidates Eliminated – 38
Eliminated due to timing – 30/38
This category contains treatments that for one reason or another would pose no threat to Leronlimab in terms of announcing topline data/ finishing trials before us. Treatments in this category possessed characteristics such as “trial initiated 05/26/2020”, or “treatment still in development” or “large enrollment size, but only 1 clinic enrolling,” etc, etc.
Eliminated due to Preliminary inefficacy – 2/38
This category contains treatments that failed to produce efficacy with result thus far. An example of this would be Avigan, which was recently rejected by the health minister of Japan for showing no clear benefit.
Definitively eliminated by institutions – 2/38
This contains treatments such as REM and HCQ that have been publicly acknowledged as ineffective or incomplete by major journals or institutions.
Eliminated due to controversy or association – 2/38
This contains PRED, which after doing a quick google search you can see that it debated whether or not it will be effective. Also contains a structural analog of chlorquine.
Eliminated Due to study design – 1/38
Single arm study.
Eliminated due to safety – 1/38
This includes a treatment (plivensia) which was rejected by the FDA for a RA indication.
Now to move on to the treatments that I felt represented a legitimate threat to CYDY in terms of when the companies would be able to announce topline/interim results or were a threat based on comparable efficacy.
It is of note that the immediate numbers below represent what the PRIMARY threat each treatments represents is. Multiple treatments were threatening with respect to timing and also had demonstrated some efficacy.
Total Candidates Threatening – 10
Threatening with timing of topline results – 9/10
This particular group was comprised almost entirely antibody-based therapeutics that targeted some aspect of the cytokine storm. 4 of these treatments had some form of anecdotal evidence to suggest that they would be efficacious in treating covid patients. Knowing what we know about the respiratory disease Covid causes, we can be sure that this is the case and that for the patients who have not progressed into full blown immunological disease that these treatments will be of benefit to them. 5 of these treatments had major side effects. Among the worst were Kevzara, Ruxolitinib and Actemra. Additionally, convalescent plasma is in this group and given what we know about plasma viremia from Dr. P’s pre-print there is a high likelihood that this will be an issue with donor units.
This group represents treatments that will most likely present therapeutic value to patients and have a chance of reporting topline results before or around the same time as Cydy.
Threatening with efficacy of treatment – 1/10
This group only had one treatment and it is a stem cell based therapy by MesoBlast. Their anecdotal evidence is reminiscent of Leronlimab’s with respect to stunning efficacy on the sickest patients. One caveat is they either have not treated or published the data regarding the use of their treatment on additional EIND patients. This treatment does not represent a threat in terms of timing. Their expected completion date of trial is in 3-4 months per their recent earnings report. Another issue is scaling, they recently raised (I think 90M$) to build a manufacturing facility. This to me means they will not be ready before CYDY to meet demand.
Important caveat is this company has stated it plans to release interim data when they reach 100 patients. They began enrolling 5.6.20.
2 Treatments there was not enough data for me to form an opinion.
The 51st treatment is Leronlimab.
Ok the rest of this will be my perspective / opinion on the situation.
Doing this much research has given me a different perspective on things. Let me start by saying I’ve visited other message boards for a few of these treatments and it is eerie how the exact same issues get discussed. Every other board has the same concerns as us. They have their bashers they deal with. They have paranoid thoughts and suspicions regarding the motives of the FDA. Again, it is eerie. But that helped me understand that fear manifests itself in similar patterns across all humans across all investments and that my focus should be on the science and timing / positioning of the company.
What I’ve also seen is that literally no other company is as transparent as Cytodyn is with regards to sharing patient outcomes in the EINDs. It’s really amazing. We’re very lucky that NP shares as much as he does. If we’re to believe that the best drug wins, then it’s obvious to me that we posses the best drug and that we are at least very competitive among the others.
Now, the overall situation we find ourselves seems to be the following –
CYDY leadership will have to decide within the next couple of weeks whether or not they wish to unblind the trial, perform analysis and submit to the FDA. This is based on enrollment speed. There’s 2 ways this
________PURE SPECULATION AT THIS POINT______
Scenario 1) enrollment picks up and trials complete enrollment by 3rd-4th week of June, TOPLINE results out by end of 2nd week/3rd week of July.
RISKS: In my opinion the primary risk associated with this course of action is that there most likely will be a handful of other trials that will release topline data before us or near us and we will lose any momentum associated with the media coverage that comes along with being the first.
PROS: Even though we would most likely lose that “first to report” momentum, it will be to a treatment that will be not nearly as effective as Leronlimab. And it will likely be to a treatment that is targeting critical/severe patients while our indication is mild/moderate. We would have the statistical strength of 75 patients and would not run the risk of the FDA asking for additional data since they designed the trial.
Scenario 2) enrollment stalls over the next two weeks, they unblind the study and submit TOPLINE results by 3rd or 4th week of June.
RISKs: The risk associated with early unblinding is losing the statistical strength associated with the full enrollment and not completely fulfilling the parameters of the FDA’s trial design.
PROS: IF our results were absolutely over the moon off the charts stunning, it would be hard for the FDA to demand more info given the safety profile of Leronlimab.
In either case, how do we know Leronlimab will be effective for mild/moderate patients?
First, we know it is effective with just the absolute worst of the worst. So it’s logical to assume that it would be effective on m2m. Beyond assumption, it’s clear that Dr. P’s paper correlates the administration of Leron to it’s MOAs that then support the clinical outcomes we were seeing with the patients that were “on death’s door.”
But to take it one step further and analyze a recent study and perhaps extrapolate efficacy of Leron, I look at this.
https://www.ncbi.nlm.nih.gov/…/a…/PMC7177...bl0002/…
This is a study where Baricinitib (a JAK inhibitor whose function is to reduce or reverse lung inflammation) was administered to patients already on ritonavir-lopinavir (repurposed protease inhibitor) and respiratory parameters were measure at 1 and 2 weeks compared against a Standard therapy only group (NOT EVEN PLACEBO;ritonavir-lopnavir).
After two weeks what they observed were statistically significant improvements in the following in the Baricinitib group OVER the SOC group. AGAIN this is being compared against a SOC group, NOT a placebo group. A placebo group would’ve done even worse and that statistical significance would’ve increased for these and other parameters:
Cough
Dyspnea
Fever
Sp02
Pa2/Fi02
CRP
MEWS Discharge %
Now if you refer to our M2M study you’ll see that the primary outcome measures are
myalgia
dyspnea
cough
for fever
Now if you reference Dr. P’s pre-print you’ll see that there is a clear reduction in IL-6 and viral load. Dr. P has also mentioned that other inflammatory markers decreased and that they’ll most likely be included in follow up papers. Rantes is one such marker I’m sure will show up in graph displays in future papers.
So here’s my point with referencing this other study.
The study, though not placebo controlled, showed that Baricinitib which only posses one MOA was able to cause statistically significant improvements in M2M patients over those using SOC in THE SAME parameters that our study is measuring. So knowing what we know about Leron’s MOAs (decrease Cytokine Storm, restore immune balance, reduce viral load), is it likely that Leron will also cause statistically significant improvements in M2M patients in the same parameters?
Yes.
Whichever path they choose with regards to either unblinding early or waiting for enrollment, I’m very confident that we will see statistically significant improvements over PLACEBO in the parameters they’ve outlined. That is not a concern to me.
Conclusion
We are literal weeks away from a conclusion. It will get turbulent, have no doubt about that. Shorts know that TOPLINE results are not too far off. You will see SP suppression, lies, etc. coming out left and right. I guarantee other message boards will show the same thing over the next few weeks.
My perspective is that Leronlimab, out of 50 other treatments is the only CCR5 blocker. It is the only treatment with multiple MOAs that address each aspect of Covid. It has a well proven safety profile.
In my opinion, if we wait for trial enrollment (so long as it is moving forward) that is our best option. The worst consequence of this course of action is we share the limelight with 2 -3 other antibodies that are one dimensional in their approach to treating covid.
The only other most effective treatment is unlikely to beat us to the punch, and even if they did, they are still building their manufacturing facilities and won't scale like we can.
Odd balance right? Those that beat us to TOPLINE aren't as effective OR safe. The treatment that is AS effective and AS safe as us, won't beat us to the punch.
After evaluating the competition, my conclusion is that Leronlimab is STILL in a class of its own.
Hold tight everyone.
ONLY IMO!!!
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