Leronlimab's Expanded Reach

IMO, Merck or any BP is going to buy us not because of some event (Maybe the immune activation trial results) but more because the BP needs to participate in the growing trend of immune modulator market*.*

I'll take it from here my good friend u/Upwithstock. What a beautiful post.

He outlines many good reasons for BO that on the verge of execution and he spells them out before they happen, so that later he may sing, "I told you so". Sure, these prognostications could unfold before us just like he says is a possibility and thanks to him, we can be ready when and if they do. What he spells out should be paid very close attention to.

Why is it necessary for the upcoming clinical trial in ImmunoModulation to even take place?

Welcome to all of you here that are pursuing this in a serious manner. Look at this as a Class Room, as I give you my handy-dandy notepad that I use to track what is happening. But remember, go back and read the references yourself, then ascertain your own guidance and discernment from what you've learned. Thank you for allowing me to pester you like this.

Why is the upcoming clinical trial in ImmunoModulation so vitally important? For the time being, CytoDyn has abandoned all specific indications in HIV except one. This is the only one which was selected to be pursued:

"00:03:45, Dr. Jacob Lalezari:

I'm also excited to announce that CytoDyn submitted a new phase two protocol to the FDA to evaluate the effects of 24 weeks of leronlimab on chronic immune activation and inflammation in cisgender men and transgender women living with HIV. This protocol was submitted in early November alongside the company's response to the partial clinical hold. Chronic immune activation and inflammation cause strokes, heart attacks, and other vascular events and remain the leading cause of death in people living with HIV. The FDA letter of November 30th, in addition to lifting the partial clinical hold, also provided extremely helpful guidance on CytoDyn's proposed immune activation protocol in order to help optimize our chances of success while taking aim at this complicated therapeutic challenge and critical unmet need."

The immunoregulatory and immunomodulatory capacity of the CCR5 receptor blockade leronlimab is a mechanism of action of leronlimab consistent throughout all the inflammatory diseases it is indicated and considered in. Why is that? Because CCR5 is a chemokine responsible for the recruitment of certain white blood cells that govern the immunoinflammatory cascade. By controlling these WBCs, leronlimab becomes an immunomodulator as WBCs run the immune system. But, they are controlled by CCR5 and leronlimab controls CCR5. While CCR5 is not found on a certain WBC namely, neutrophils, that means that the blockage of CCR5 has no effect on neutrophils, so therefore, neutrophils may still do what they do against infection, which is kill bacteria, fungus, mold and mildew. Leronlimab does not impede their action. "Neutrophils are polymorphonuclear and granular leukocytes that function as an essential part of the innate immune system*.*" But CCR5 is definitely expressed by macrophages, which are more a part of Adaptive Immunity and by blocking the CCR5 expressed on the surfaces of macrophages, the response of the Adaptive Immune system to an invader becomes modulated which leads to a tapered inflammatory response when necessary and an increased inflammatory response, also when necessary. Also, leronlimab modulates the healing response similar to the inflammatory response, it is also increased or tapered based on need.

Yes, we know that in HIV, leronlimab blocks the entry of HIV into the CD4 T lymphocyte, thereby preventing infection. But it also has this immunomodulatory capacity, and it is this capacity that is consistent in the rest of the diseases, and it is this capacity which is sought after by BP industry and by the BP NDA. CytoDyn shall have the victory. CytoDyn already has the data proving leronlimab can do all of this.

As u/Upwithstock reminded us, they have the MD Anderson study results. Who was bb referring to here? "One last tidbit: a world renown cancer center wanted to be involved and handle all testing*, but the powers at Cytodyn turned that down as well.*" Why wouldn't CytoDyn want MD Anderson to handle the testing? Maybe CytoDyn wants Merck to handle it all? Maybe Merck wants to handle it all?

IMO, it would have been premature to engage in that CRC trial with MD Anderson without first being able to understand the intricacies of the CCR5 function more completely. Sure, we know leronlimab would succeed against CRC as it was shown to do that in the Basket Trial and MD Anderson saw it themselves in the Keytruda study. However, first things first. It is necessary to know first, exactly how leronlimab is an immunomodulator, how it does what it does. Could this lack of information have been the reason why CytoDyn turned down the CRC study requested by MD Anderson? And to this end, the assembly of the biomarker data is necessary. MD Anderson wanted to take the labs. But they didn't know which labs. The assembly of the data needs to be done by AI. I think u/Upwithstock 's point on AI here is well taken.

"CYDY announces they have a AI partner, but the NDA won't allow them to announce it at this time. One thing that is unusual about this AI? CYDY NDA; generally speaking: if CYDY is working with an AI company, CYDY is the customer, and we would have to pay the AI company to produce information for us. But that does not seem to be the case with this relationship. CYDY does not have money to pay for AI services. So, who is paying the AI company to produce information for us? Could it be Merck and their AI relationship with AI company called ABSCI located in Vancouver, WA? IDK, but I am willing to bet on it. "

CytoDyn has performed many trials. It has substantial data, mostly in HIV, but it also has data in other indications as well. Almost every trial or study was promising. The cumulative data has been aggregated. The prior hold put some of that information in the hands of the FDA. So, CytoDyn has broken through the easy part in showing that leronlimab is safe and effective in a multitude of indications. Now, the FDA is requesting information which shows leronlimab's capacity as an immunomodulator in NASH. CytoDyn is now working on the far more detailed and difficult next step, requested by the FDA, which is: what makes leronlimab tick? What is it about leronlimab which makes the mechanism of action consistent in all of those indications, that leronlimab is an immunomodulator?

Dr. Lalezari wants to put out the data which CytoDyn has accumulated over the years. He wants to put it out in peer reviewed journal articles.

"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.

The CD02 study, I believe, has been tentatively accepted, pending release of the clinical hold. So we expect to be able to move forward with that very quickly. I'm obviously someone who's been very interested in the COVID data. And we're going to make a priority of getting CD10 and CD12 published.

00:33:19, Dr. Jacob Lalezari:

I've also recently reviewed the cancer data. And it is urgent that we get CD07 published for that, again, provocative single benefit. So publications are getting a protocol finalized, off hold, begin the process to implement, get these publications, including the NASH study, the long COVID study, submitted for peer review. I had talked to folks at NIH some years ago about our COVID data in the ICU population. They've been waiting to see the data in a peer reviewed format. And so that's a huge priority for me. And then at the same time, there's no reason why we cannot aggressively pursue partnerships to extend the research platform for leronlimab. And I will commit to that wherever that makes sense. So those are the significant events that, you know, I'll be looking for over the next, you know, two to six months."

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"00:25:36 Dr. Jay Lalezari:

I think that's a study that the FDA is going to have a hard time not wanting to see done. There is currently no therapy for immune activation in HIV. Half the patients we're going to enroll are going to be transgender women who have elevated activation markers because of the hormonal therapy they're taking. And in fact, what I had mentioned earlier was that the FDA, having received the protocol, has asked if they can cross-reference the IND file for NASH, which is exactly the right question to be asking is “what other evidence do we have that leronlimab is mediating inflammation and immune activation?**”

​

So, the next step, after proving that leronlimab is safe and effective in all these indications, is that the FDA wants to see the evidence that proves that leronlimab mediates inflammation and immune activation or in other words, the FDA wants to see the evidence proving that leronlimab is an immunomodulator. CytoDyn has submitted this already, but now has to prove formally this immunomodulatory capacity in a phase II clinical trial. This is the "general" picture, which is what CytoDyn is working on now. The first submission of the protocol for this trial should be done by end of January, 2024.

Yes, CytoDyn submitted the "Inflammation and Immune Activation" Indication which the FDA was receptive to after going through the 5 HIV indications that would still benefit with leronlimab treatment. This is what was selected. As u/Upwithstock has suggested, could this have been by Merck's recommendation? Maybe that is why Upwithstock contemplates the possibility that the bid could be made before the end of the trial.

When this trial completes successfully, it shall prove outright that leronlimab is the most versatile drug in the universe. It proves beyond a shadow of a doubt that leronlimab may be incorporated into almost every treatment out there to enhance and augment the original intended purpose or to reduce the unintended side effects. Maybe that is the underlying reason for the BP NDA which is being contemplated. Once this MOA is determined via the equation (which is why AI is necessary), it cannot be undone. It proves once and for all that it works in such and such a manner and there is nothing they can say or do that would undo that truth.

CytoDyn and the BP NDA are taking the necessary steps to gain the FDA backing and support for this immunomodulator. There are many fronts upon which CytoDyn is fighting, but all have one goal in mind, leronlimab approval. CytoDyn is relying on Sidley Austin to fight with Amarex, the previous CRO that purposefully sabotaged the drug and the company for their personal and their master's gain. SA is confident for a significant win in excess of $100MM. Due to matters centered around efficiency, all other efforts have been put on hold until the resolution being the lifting of this new hold is also completed. Then this new trial commences. Then, in the midst of that trial, after a sneak peak of the data, a BO bid is made.

This is the life changing moment for CytoDyn. An agreement that forms a covenant between CytoDyn and the BP NDA which is forthcoming and inevitably occurs which thereby allows shareholders to rest assuredly in peace and safety. All this happens because leronlimab's MOA has been furthered and progressed by this trial. It has been expanded and the data has been extrapolated to prove the anecdotal evidence of the manifestation of this drug's immunomodulatory capacity. The work which leronlimab achieves shall be further evidenced by this trial and this work which proves this leads to this moment.

This work shall allow leronlimab the versatility to be used in countless manners. Almost as an additive that would enhance or improve the function of the other drugs. Maybe, the entire BP industry would be able to share its use?? Maybe the BP NDA might be permitted to use it in combination with its existing drugs? The point here is that this trial greatly expands leronlimab's reach.

So, we know that this is about to happen. It is being set up as we speak. We are embarking upon an endpoint that nobody has yet pursued. We know CytoDyn satisfies this endpoint based on previous work and prior data that is yet to be distilled into peer reviewed articles. So, this becomes CytoDyn's Purpose. All of what has happened to CytoDyn has happened to get us here. It is all in Progress. We will keep an eye on it unfolding in the direction and to the end which u/Upwithstock and I have hypothesized upon.