Another Season Awakening

Let me assemble something here at this junction.

CytoDyn finds itself placed in sort of a corner. At least, from my perspective, it seems to be somewhat pickled in. I know absolutely though, that there is a way out, but really, only one way out. So, that becomes how it happens. That it therefore must take place.

At this point, with leronlimab now considered as "Safe" by the FDA, CytoDyn again wields its multi-edged sword. In consideration of all the indications leronlimab could treat, so then that becomes the number of edges the sword wields. The weapon is sharp, yea, very sharp. It can slice and dice over and over again, into many, many cut up pieces. Therefore, take heed, those who decide to come upon against it in opposition or competition, should think twice and consider backing away from competing within leronlimab's space. Because, when push comes to shove, leronlimab dices up its competing enemies.

Let's show a small portion of what has already been seen of what leronlimab has been trialed for.
Let's consider a few of leronlimab's prior trials. In HIV, CytoDyn actually submitted a BLA for HIV-MDR. In the trial, a p-value of 0.0032 was achieved and that is why the BLA was submitted. Despite the multiple reasons why the FDA did not accept the BLA, the point I make here, is that the p-value in keeping HIV at bay in individuals who were resistant to multiple anti-retroviral treatments was achieved 16x above minimum threshold. 0.05/0.0032 = 16. The resulted clinical trial in HIV-MDR is here in ClinicalTrials.

Another trial was in metastatic Triple Negative Breast Cancer. This Clinical Trial in mTNBC has as its conclusion "These studies suggest that mTNBC patients dosed with leronlimab had high clinical benefit*,* i.e. longer Progression Free Survival & Overall Survivability with few Treatment Emergent Adverse Events, and leronlimab resulted in a drop in circulating Tumor Associated Cells in the majority of patients correlating with early therapy response*.*"

On the MASH front, the NASH/MASH study revealed a significant reduction in NAFLD and a reduction in liver fibrosis using leronlimab. This post is a transcript of the ProActive Video discussing NASH and a little on COVID. This is the press release stating that Leronlimab 14-Week, NASH Clinical Trial Met Primary Endpoint (PDFF) and Secondary Endpoint (cT1) for Per Protocol Population in 350 mg Weekly Dose where the Primary endpoint (PDFF) was achieved in both Intention to Treat and Per Protocol Populations. Thank you u/u2rocksme, where he elaborates, "The primary endpoint, PDFF (proton density fat fraction), is an MRI-derived biomarker for fatty deposition, while the secondary endpoint, cT1, is an iron-corrected T1 mapping representative of liver inflammation and fibrosis. These two values are used to evaluate the effect leronlimab has on NASH. CytoDyn’s Phase II clinical trial compared the changes from baselines in these endpoints. The leronlimab 350 mg dose versus placebo comparison for the primary endpoint PDFF was statistically significant. BOTTOM LINE TO BE VERY CLEAR>>>LERONLIMAB 350 MG DOSE WAS STATISTICALLY SIGNIFICANT!!!".

Here the BioMarkers measured within the NASH Trial give some indication as to how leronlimab might reduce Inflammation.

Jumping now to COVID-19, Dr. Lalezari while speaking to the NIH has this to say. It speaks as to leronlimab's performance and CytoDyn's performance in the COVID trial. Dr. Lalezari does a good job describing how the trial was not fairly designed, yet it was accepted by both Nader as well as the FDA.

This is only a small sample of where this drug has been.

Lastly, I jump to this post to illustrate where we are headed. I say we are headed in this direction because of statements like this taken from 12/14/23 Webcast:

"I therefore believe that in order to move forward, CytoDyn needs to strategically pivot, which means moving away from leronlimab’s antiviral activity, blocking HIV entry and toward what we hope and believe to be leronlimab's true major contribution to Western medicine in its role blocking chemokine signaling through the CCR5 receptor.

So what evidence do we have that leronlimab can block signaling through CCR5 and provide meaningful clinical benefits to patients? The clinical results from the CD12 study in COVID, the CD07 study in triple negative breast cancer, and the NASH study all provide provocative preliminary signals that leronlimab could provide clinical benefit in these settings.

00:21:14, Dr. Jacob Lalezari:

Now, to be absolutely clear, the studies conducted to date do not provide definitive proof or statistical confirmation that leronlimab works. But it is curious to note how the provocative signals that leronlimab might be working are occurring across a variety of very different medical conditions in which CCR5 appears to play an important role in the disease being studied.

Which is why I believe it makes sense that CytoDyn’s next study directly evaluates the long-term ability to modulate immune signaling through CCR5 in HIV-positive subjects, a population for whom immune activation is the main driver of mortality, and a population in whom we already know leronlimab has been well-tolerated.

As FDA directed in their letter, this will be a double-blind, placebo-controlled study to evaluate leronlimab's impact over 24 weeks on activation losses in both cis-male and trans-female HIV-positive subjects with increased levels of activation documented at screening.

00:22:41, Dr. Jacob Lalezari:

I believe this is the most cost-effective way for CytoDyn to proceed and directly test leronlimab’s most important and potentially most valuable mechanism of action."

Remember, as it were, in days gone by, I had said repeatedly, that we would know what to expect based on fact that, whatever was happening at the time would point to that which we could expect would happen next. Over and over again we said that the hold would lift and eventually, the hold did lift. Yes, a second hold was imposed, and again, we claimed once again that the second hold would lift. We knew for a fact that it would happen, it was not necessary that we be told ahead of time that it was coming, and lo and behold, the second hold too was lifted as well as the first.

In contrast, Mazzy Star said over and over, yes, much more that a multiple of times that the hold would never be lifted, and she was proven wrong over and over again. Now she is gone, at least reduced. Is this a surprise to anyone? To me, it is not a surprise that she was wrong, but it is a surprise that she is gone, but it is much, much better that she is.

So, now, we find ourselves in a similar situation where we need to know, "What comes next?". Given u/Upwithstock's recent post, where many things are required just to initiate the clinical trial, it is not explicitly clear exactly what we should be expecting CytoDyn's next step definitively to be, however, that should likely be discussed in the upcoming quarterly conference call, the date of which is yet to be disclosed, but probably could be held on Tuesday, April 9, 2024. (This is just my guess as to the date). Thanks to u/Upwithstock, we can expect information on what he laid out in his post, which pertains to the logistics of the Trial Protocol, to the logistics of the publication of Manuscripts and on the discussion matter of any brewing Partnerships. So, u/Upwithstock as well as I and a good number of other posters point to various reasons why we can definitively know and confidently understand what it is which comes next.

Leronlimab has proven itself, at least anecdotally on multiple fronts. Now, that the data has been validated and verified, thanks to the work of Cyrus Arman, Chris Recknor, MD, Bernie Cunningham PhD, Joseph Meidling and many others, much of that anecdotal data has been transformed into tried-and-true scientific clinical data employing the FDA techniques of Good Clinical Practices. This transformation of leronlimab's data from anecdotal to clinical and scientific data happened simultaneously with the transformation of the old CytoDyn to the new CytoDyn marked mainly when Cyrus cleaned house, including the removal of Chris Recknor, MD. Possibly, Cyrus was making a statement that this is no longer the old CytoDyn? The various articles on the indications listed above and more which I have not listed, were originally written using the anecdotal data, thereby nullifying them in the eyes of the FDA. However, now they have been re-written as manuscripts using the FDA Good Clinical Practice Format with the validated scientific data and these manuscripts are being submitted now for peer review and followed by subsequent publishing as journal articles. This is at least what Dr. Lalezari is aiming for, and since his arrival, I think we can take him at his word. Once these manuscripts are published, it then becomes possible to make the statement that Leronlimab has proven itself clinically and scientifically and not just anecdotally.

So, is it unreasonable to believe that scientific proof alone can lead to partnerships? Proof of what you ask? From the Webcast 3/5/24

"6:25: I believe the inflammation study as described is the most cost-effective way to clearly establish leronlimab's biologic mechanism of action. If successful, I believe such studies would create the opportunity to intervene or partner in a host of other inflammatory conditions*. Establishing proof of leronlimab's activity as an anti-inflammatory, could also create the opportunity for CytoDyn to study its potential to reduce heart-attacks, strokes, and other inflammatory vascular events which remain the #1 cause of death in people living with HIV."*

Let's look at the indications of the 1st (4) manuscripts? 1) (2) manuscripts on metastatic Triple Negative Breast Cancer; 2) a manuscript on CytoDyn's clinical trial on HIV-MDR, Multi-Drug Resistant and 3) a manuscript on CytoDyn's underpowered clinical trial on COVID-19. With the peer reviewed published journal articles coming forth in the indications in the order listed here, with FDA backing, these documents lay it out there, proving to any potential partner that leronlimab is 1) safe and effective against mTNBC, 2) safe and effective against HIV and 3) safe and would have been effective against COVID-19 had the trial been properly designed and approved. mTNBC comes first two times. Then HIV comes second, while COVID-19 comes third. From the Webcast 3/5/24

"12:08: In terms of Partnerships, I'd like to affirm our ongoing commitment, to pursue partnerships and give leronlimab multiple shots on goal, to prove itself. The Board and Managment are currently evaluating several options on how to proceed as to obtain to oncology, MASH, and other potential indications. For example: we are acutely aware of the continuing and even growing interest in long Covid and will continue our efforts to bring attention to leronlimab and to possible partner in the long Covid treatment strategies.

12:48: I would also like to note, the growing body of evidence implicating the role of Inflammation and specifically CCR5 in the pathogenesis of Alzheimer's disease. This is obviously an area of enormous and urgent unmet need and given the long safety profile of leronlimab to date, together, with data, from a recent pre-clinical study, suggesting that blocking CCR5 might rescue memory deficit, I believe pilot studies in patient Alzheimer's disease is now justified."

So, given the fact that this certainly is Dr. Lalezari's intention to deliver on these manuscripts and to deliver on this trial and given that the authors there at CytoDyn were not sitting on their asses all this time only working on the lifting of the holds, but certainly were doing the Preparatory work which would become necessary once the holds would expectedly be lifted and some of that work surely included the re-writing or the re-hashing of the articles into the referred to manuscripts which use the validated data. Therefore, as we have done before, so we can do again. We can certainly expect and even know that these manuscripts do become peer reviewed and published as journal articles. In the order Dr. Lalezari has already outlined, we can know this to happen, and we can expect this exactly like we expected the holds to be lifted.

So, now that we are over the lift of the hold, we enter into another season. So, the hold was lifted, and now, CytoDyn finds itself in a predicament. However, there is an answer. There is a way out. The way out is via execution of the logistical work u/Upwithstock outlined in his post. Starting with the Investigational sites, then the meetings with the Internal Review Boards and all the minutia he discussed, it needs to begin happening as he stated. If not already done, CytoDyn needs to determine who their CRO becomes. In the comments of his post, hopeful speculation was made that it possibly could become our own Scientific Advisors that perform the work of the CRO in the coming Phase II clinical trial and if that were to happen, it could be a massive cost savings to CytoDyn, but regardless, more information on the trial should come out on the quarterly conference call.

So, the objective of all the Preparatory Work is to get the clinical trial for Immune Activation and Inflammation underway. The main thing about this trial is that it proves leronlimab's capacity to Attenuate and Mitigate Immune Activation and Inflammation across individuals who have severe and chronic Inflammation. Although CytoDyn has already been for years and years, completely aware of leronlimab's capacity to perform in an anti-inflammatory fashion, CytoDyn has never pursued this indication directly for leronlimab. CytoDyn has always targeted the disease itself. For instance, some of those diseases/indications are HIV, mTNBC, colorectal cancer, COVID-19, long-haulers to name a few. CytoDyn however, has never pursued a clinical trial that proves leronlimab is capable of Attenuating and Mitigating Inflammation and Immune Activation in severely Inflamed individuals. This is something brand new, not just to CytoDyn, but to the world and that is why this trial is so important to CytoDyn. This then becomes the source of motivation for Dr. Lalezari and everyone there at CytoDyn. They are all now working towards the initiation of the coming trial in the Attenuation and Mitigation of Inflammation and Immune Activation in severely and chronically Inflamed individuals.

This Immune Activation and Inflammation trial is something that CytoDyn's competition does not want to see happen or be fulfilled. There are many reasons why the competitors would very much prefer that leronlimab fails this trial. They would certainly prefer, that CytoDyn pursue another indication, say, mTNBC or colorectal cancer, but not Immune Activation / Inflammation. Why? Because the indication is a very broad one. It is miles wide. Yes, CytoDyn plans on executing the trial in extremely Inflamed individuals that are HIV+, but it is not doing the trial for the purpose of treating HIV. No, it is doing the trial to measure how well leronlimab Attenuates and Mitigates the level of Inflammation and Immune Activation within anyone who is severely and chronically Inflamed. That is a MASSIVE indication.

So, little by little, CytoDyn works towards getting the trial underway and where they are at should be disclosed on the coming quarterly conference call. Part of the problem CytoDyn has is how is the trial financed? Well, if u/Upwithstock is right and the remote chance of having our own Scientific Advisors as the CRO, then the trial could be financed for much less than we could ever hope. But, if a real CRO is decided upon, I don't see the trial costing for less than $25K per patient and there shall be 90 patients in the trial. Therefore, in my eyes, if we are to use a full-fledged CRO, then it doesn't cost less than $2.25M for the trial. So, that is a part of the reasons why I say CytoDyn is backed into a corner. They get out of this problem though, in non-dilutive ways, because we know what Dr. Lalezari has said and in what direction he leans toward and aligns with. He is pro-shareholder and pro-partnership.
From the Webcast 3/5/24

"13:28: The challenge of course is that CytoDyn is just emerging from a (2) year clinical hold and doesn't have the resources to do everything we would like. We are also keenly aware of the need to stay focused and not trying to do too much all at once. With that said, the Board and Management are working closely together to identify our priorities and the appropriate next steps to proceed. To that end, we will be taking steps to ensure the effective and efficient use of our resources while incorporating funding through 3rd party sources wherever possible. To be clear, we will be prioritizing opportunistic ways to develop and create value through various means for leronlimab and employing strategies that are time and cost effective including for example, opportunities through non-dilutive funding, license agreements, co-development initiatives and partnerships."

Consider a hypothetical situation. Once leronlimab becomes viewed by Big Pharma as an anti-inflammatory, if another pandemic were to happen along the normal course of things, leronlimab would become more readily considered, especially by the FDA, for a trial against such a viral pandemic situation. Because of the possibility of another such disaster, the COVID-19 manuscript is being produced which shows how well it could have performed, had it not been an underpowered trial, which was approved by the FDA and pushed through by Nader. I'd say that if another pandemic came along and started killing people the way COVID-19 did, with Lalezari at the helm, the trial would not be an underpowered one, but if anything, an overpowered one. It would definitively prove leronlimab's capacity to overwhelmingly allow natural healing in such acutely critical and inflammatory environments. It would prove to the world what leronlimab is capable of and not just to the world, but also to the FDA, that fake untested vaccinations are not the answer. From the 12/14/23 Webcast:

"00:32:24, Dr. Jacob Lalezari:

The other, so getting this protocol finalized, coming off hold, that's all going to happen, I think, in the very short term. I mentioned the priority of getting manuscripts published. CytoDyn is sitting on some very provocative clinical data. And the world mostly doesn't know about it. So that's a top priority."

I suspect, that as CytoDyn gets further and further into the roll out of this Attenuation and Mitigation of Inflammation and Immune Activation trial in severely Inflamed individuals, that the company begins to see opposition as the day of trial initiation draws nigh and that is because they don't want leronlimab, the anti-inflammatory in existence at all. We see them sticking their noses into CytoDyn's business. Their Big Money counterpart cabal short the shares in excess of the long buys for years and years unceasingly. Dr. Lalezari already is aware of this opposition and of their intent to increase their opposition as the days draw nearer. He knows already exactly what to do in these circumstances. He knows what he needs to do to maintain the clinical trial train on the track and what to do to keep it from derailing.

Dr. Lalezari knows the way out. Certainly, by developing leronlimab into a multi-edged sword is of primary importance and this explains the focused push towards the trial and the focus on the manuscripts. The logistics necessary to get the ball rolling, Dr. Lalezari is already familiar with such things many times over. He also knows how to get the manuscripts published. There won't be any stopping his plan, maybe slowing it down, but never halting. No, this comes to fruition, unlike what happened with the BLA when it was dead in the water when it was decided not to be pursued any further. Why is there no stopping this trial? Because CytoDyn needs, absolutely requires a multi-edged sword. This is what leronlimab really is, a knife with many blades and it absolutely must be developed as such. What does a multi-edged sword do? Does it not slice, dice and cut to pieces anything and everything that may challenge it?

So, as we can tell, it is absolutely necessary to have a certain amount of patience. Also, understanding is an absolute necessity. CytoDyn is in a situation, and I know it gets out of the predicament it is in because I know what the focus is that Dr. Lalezari has stated multiple times, but I don't know the mechanism by which it all gets accomplished just yet. But I do know, that once leronlimab is proven as an anti-inflammatory and as an Attenuator and Mitigator of Immune Activation, that alone proves the drug and proves to the world that the company CytoDyn is capable of delivering the masses from a worldwide plague or pandemic and with that knowledge, understanding and proof, who on Earth would not want to partner?

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