CYDY Investor Deck
I quickly put this together for anyone that might want a few good reasons to come in now, with the share price as low as it is. Maybe you are on the fence or maybe you know someone who is on the fence. I just put together some reasons why it may be time to commit. We saw that a R & D Update sign was given a year ago, and it was fulfilled.
Now, we can know, that this shall come to fruition. The FDA lifted the hold based on whether or not they intend on approving this protocol. Since they lifted the hold, they are intending on approving this protocol.
Leronlimab shall be approved on this massive indication of Immune Activation and Inflammation. Such a huge, encompassing indication. We already know the drug is safe and effective. The hold was lifted proving safety. Clinical trial has shown effectiveness.
Let's now take a look at some preliminary statements that point to leronlimab as an immunomodulator:
12/7/22 R&D Update: NASH & Leronlimab
"32:08: So what's CCR5? It's a G protein coupled receptors, and it's the receptor for these chemokines, where they hit and affect the cascade especially the harmful cascade. And its cognate ligands include CCL3, CCL4 and CCL5 (RANTES)**. And I showed you earlier that this important monocyte then that they turn into macrophages*, and* they activate the cascade inflammatory signal as well as eventually stellate cell itself to produce myofibroblast via CCR5 which is present on all these pathways, and CCR5 plays to this cascade mechanism. "
There is dramatic reduction in these inflammatory proteins with the treatment of leronlimab.
There is dramatic reduction in these inflammatory proteins with the treatment of leronlimab.
"41:26: There is also more analysis, and this is important, VCAM, which -- VCAM is a recruitment of these inflammatory cells. It's a marker*. So we're hitting that as well, showing that you* reduce the recruitment of inflammatory cells, monocytes and other cytokines to the liver*. And* EN-rage is a very important marker has been also decreased with these 350-milligram dose with various sub-analysis and those that they had fat and inflammation as well."
"So this looked at changes in circulating tumor cells that have been associated -- or can be looked at as a surrogate for progression of disease. And what you can see here is that the progression-free survival for patients who received at least 1 dose of leronlimab*, they had --* and those that had an absence or a decrease in circulating tumor cells, (both), had a trend for better survival than those that had an increase in CTCs. And similarly, we saw a similar sort of trend on the overall survival curve. "
"55:22: So when we look again at their tumor growth through the spyre grams and through the waterfall plots, that we only had 6 patients here. But as you can see, all of them remain within the stable disease and many actually achieve partial responses over the course of the short study. And one of them actually had no measurable lesions on the PET scan at follow-up*. And the remainder saw either stable disease or partial responses. "*
These are Chris Recknor's words from the 6/30/22 Conference Call Scott Kelly and Chris Recknor:
"24:25 Chris Recknor: Thanks Dr. Kelly and thanks for the investors calling in. We've made good progress on investigating the MOA of leronlimab and wanted to give an update. We believe that leronlimab may work in several different ways and understanding how leronlimab works informs us about potential clinical developments, and helps us to identify key strategic partners that synergistic opportunity looking for key biomarkers and MOA. Dr. Kelly mentioned the issues that HIV patients have with liver inflammation and it is significant*.*
The mechanism for preventing HIV for viral entry for leronlimab is thought to really to coding or binding CCR5 to prevent HIV from entering the cell and in our Phase 3 HIV trial Optimize, we showed a reduction in plasma HIV w/ leronlimab 350mg vs. placebo with a p 0.0032 that extended to a 24-week extension phase where by 80% of patients remaining in follow up had HIV RNA levels < 50 copies/ml. The interesting thing is they also had improved CD4 counts. So, in addition to viral entry inhibition, leronlimab appears to work as immunomodulator, such that at lower doses, it may reduce inflammation but yet at higher doses, may affect immune system by increasing CD8, the natural killer cells. This places our company in the unique position to be able to look at those pathways where most drugs aren't able to perform.
There are 2 places where leronlimab can bind CCR5. And the inflammation or immunomodulation may work by (1) leronlimab binding simultaneously to 2 regions on the CCR5 to alter the geometry of the receptor and enhance its function. So if you have higher doses, or amounts of leronlimab in an individual binding in a 1:1 ratio, meaning (1) leronlimab for each binding site, may lock the receptor in place without a conformational change. And we are investigating how this works in the lab, but it is interesting, because, we are looking at different doses and seeing different ways that leronlimab can work.
...
Leronlimab binding to CCR5 is thought to be essentially associated with alterations in CCL5 or RANTES and then NASH in this exploratory biomarker analysis, showed that leronlimab reduces CCL5, and other chemokines CCL2, 3, 11 and 18. These chemokines act as a beacon to attract other cells in the area. The difference is really big because we thought we just worked on CCR5, but we are also working on CCL2, 3, 11 and 18. In NASH studies, we can see correlation b/w CCL3 which is Macrophage Inflammatory Protein Alpha 1 levels and they increase in severity of NASH on biopsies. So patients in full blown NASH, show highest levels of CCL3, but leronlimab reduced CCL3 with 350mg compared to placebo from baseline from week 14. CCL2 is another one that moves monocytes, called Monocyte Chem-Attratic Protein and is a key biomarker associated with NASH. Leronlimab reduced mean CCL2 from baseline to week 14 in 350mg group compared to placebo.
Now when dr. Chung was talking about HIV and NASH, this has great application, because CCL2 applied to the treatment of the HIV patients is important because lower CCL2 levels correlate with less viral replication in effect to macrophages, less rapid feeding, of the latent HIV reservoir and less chance HIV central nervous system invasion. The ability to reduce CCL2 may have application to HIV and NASH and may really position leronlimab very effectively now to outpatients.
Once other key biomarker is molecule Vascular Cell Adhesion Molecule VCAM is very important because VCAM allow immune cells to migrate through blood vessel walls. We did not know that leronlimab reduces VCAM until NASH, but now we have now observed a reduction from mean change to baseline in week 14 for the NASH 350 mg for VCAM and this is important because it has application to other inflammatory markers that are reduced. So further trials need to be conducted with larger numbers, but the exploratory biomarker analysis may be very relevant for informing about future research in other disease states including cancer. Dr. Kelly can you provide an update in oncology."
Here is Scott Kelly from the same conference call:
"36:07 Scott Kelly: Sure, I'll take the positive news on the Science 1st. We are very encouraged by the fact of leronlimab on the biomarkers and NASH. Many of these same biomarkers are supported by the literature to be important in our oncology program including CCL2, CCL5, CCL18, VCAM and VEGF. Some of these biomarkers also correlate with the potential to decrease metastasis, control the tumor microenvironment and correlate with antifibrosis and NASH. We are also seeing some potential benefits of certain biomarkers in cardiovascular disease."
CCL2, CCL3, CCL11, CCL18, VCAM & VEGF All Reduced
So, that was the beginning of the proof that leronlimab reduces inflammation while increasing immune activation. It has a dual function of quelling inflammation while at the same time increasing capacity to fight off disease. That is why it is considered now an immuno-modulator. More has to be proven. And that is the purpose of this upcoming trial.
From the Investor Meeting late November, 2023:
"So I'm encouraged, again, like COVID, it's a signal, it is unproven, it needs to be absolutely confirmed in larger studies, and that's true of both COVID and NASH, and certainly everything that's been claimed about cancer. But what we're seeing here is two provocative signals in that telling us that in the realm of leronlimab activity in the biology of CCR5, something might be happening*, and something with* significant clinical impact*. So what is the* next study that CytoDyn can do to come off clinical hold and generate data that's not ambiguous, that tests this hypothesis around its activity in affecting signaling through CCR5*?*
00:24:03 Dr. Jay Lalezari:
And the consensus with the HIV consultants has been that we look, go circle back to HIV*, but instead of looking at leronlimab as an antiviral,* we are looking now at leronlimab as a modulator of immune activation*.* Is that a relevant endpoint? It is*, because* immune activation inflammation is the primary driver of mortality in HIV patients. Strokes, heart attacks, liver, kidney. It is unfortunately a much more difficult endpoint to assess than simply following an HIV viral load, but it is kind of in the wheelhouse of what we're believing leronlimab is capable of. So the proposed next study is to look at leronlimab in HIV positive ambulatory subjects. We know it's safe in that group. In individuals who demonstrate elevations of immune activation markers. So known evidence of immune activation inflammation. And then we're tentatively looking at both doses 350 and 700mg and looking at a nested placebo arm so that at the end of 24 weeks of treatment, we can at least get a real measurement of whether leronlimab has moved the needle there or not*.*
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 that we are waiting to hear. ...*"
From the Question and Answer:
"Dr. Jacob Lalezari:
Well, I'll just start by saying there is no treatment for immune activation in HIV*, so it's actually considered* a very large market*.* All patients with HIV are having to deal with some level of immune activation and inflammation, which is the driver of their increased mortality*. I think that NASH and cancer are very appealing markets, but way beyond the can of CytoDyn at this stage to really make inroads in on their own. They're going to have to partner. And I think it will be a lot easier to partner* when leronlimab has a proven role in reducing immune activation, the inflammation, proven role in affecting the biology of CCR5."
...
"00:31:10 Marta:
Thank you. So the next question ties to your response directly. What is the timeline to hear back from the FDA regarding the lift, and what are the next steps if the hold is not lifted?
Dr. Jacob Lalezari:
Yeah. Well, that's a question I've been dreading. And I fully expect them to approve this protocol*. There's* no reason for them not to*. There are no safety issues in the ambulatory HIV population.* There's a completely unmet medical need. And so I don't see a reason why they would reject this*. And I am not really prepared to discuss what Plan B looks like. CytoDyn does have some options under that scenario. But I prefer to think positively and think that* this is giving FDA the very thing they wanted to get CytoDyn off hold. They asked CytoDyn to identify an HIV population to use leronlimab in that was not multi-drug resistant. resistant where there was no unmet need. So I think CytoDyn has done a good job identifying this population and getting it to FDA. I don't see any reason why they have to reject it*.*"
...
"00:47:30 Dr. Jay Lalezari:
Marta, can I just add to that? When I listed some of my, what I see as my responsibilities as interim CEO, I listed oversight and accountability*, and where I see that coming into play specifically is this issue, that in the past,* CytoDyn has run studies, as we all know, that have generated provocative signals*, but nothing definitive that you can go to the bank on. When I think of* the next clinical study for CytoDyn, not only do I think it's got to be something that the FDA buys into, but it's got to be designed in a way that there is a clear answer at the end. Now that answer may be no, but I don't think CytoDyn can afford to scrimp on dollars and do another study that leads them to yet another ambiguous place. However long I'm here, I want to make sure that happens.**"
...
"00:49:00 Dr. Jay Lalezari:
I haven't done a market analysis, but the HIV population is aging. When I started as a young man with Pro140, the average age in clinical studies is around 38 years old. Twenty years later, it's still the same, you know, it's 20 years later. And those older individuals with HIV who have had the virus now for several decades, their risk is cardiovascular inflammation, immune activation. So even though I can't give you a number, I know that it's significant. And that's something that we probably need to be prepared to answer the next time we do one of these calls."
From the recent 12/14/23 Webcast Dr. Jacob Lalezari & Tyler Blok :
"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.
00:04:45, Dr. Jacob Lalezari:
Now, to be clear, CytoDyn was again placed on a new clinical hold for the immune activation study while we incorporate FDA feedback and prepare a revised protocol*. I want to stress that this new clinical hold is often a normal part of the FDA review process on newly submitted protocols. The hold does not raise any new regulatory or safety concerns and it will be removed after we respond to FDA's guidance concerning our protocol design, primary and secondary endpoints, and stopping rule.* We're reviewing the FDA guidance now with our key consultants and expect to submit our revised protocol in January*.*
00:05:40, Dr. Jacob Lalezari:
So, just to summarize and be clear, the partial clinical hold over the last 22 months has been removed and all past issues have been completely addressed. We expect the new hold to be lifted after we incorporate FDA's recent suggestions and submit our revised immune activation protocol in January. After that resubmission, the FDA will have 30 days to respond to comments*. I know that the simultaneous removal of one hold and the imposition of a new hold can seem confusing. But I want to assure everyone today that this is all very good news for CytoDyn, and we are excited to be turning the page and moving forward."*
...
"We will work through the holidays to revise the protocol and submit to FDA in January. If everything goes as planned, we then hope to launch this trial in crucial next step this summer*."*
...
"So you know, I think I have a solid understanding that we're actually finally engaged in a collaborative relationship with FDA and that they are helping us do everything possible to move past this latest clinical hold. And, I don't think it's going to be a huge challenge, I think pretty much everything the FDA asked for have made a lot of sense to me and would be fairly easy to implement in our revised protocol.**"
...
"The revised protocol, we worked through the holidays, we will get it to FDA in January*. I don't want to commit to an exact date, but it is obviously* priority one*. Once we have* agreed with the FDA on what this protocol should look like, that will result in lifting the clinical hold and we will begin the process operationally of implementing the clinical protocol, identifying our CRO, raising the necessary money, which, by the way, is much less than what would have been needed had the company pursued a study in MASH.
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*."*
By prior clinical studies, enough evidence has come that demonstrates that leronlimab is an excellent immunomodulator. CytoDyn has had discussions with the FDA regarding a protocol for an HIV trial that will prove leronlimab is capable of reducing the inflammatory effects of long term ART use. We can know that this protocol will be approved by the FDA, just like we knew that the FDA would lift the hold. Given that they lifted the hold, the FDA was satisfied with the submitted protocol for this trial and now, it is only a matter of tweaking before it is approved.
This trial will prove to the world that there is only one immuno-modulator that also has a dual function in blockade of HIV virus. Given leronlimab was just removed out from clinical hold, it goes without saying that leronlimab is safe. So, it is just a matter of time and execution. Once the right amount of time is put in, the appropriate investment is made and the studied execution of the trial is undertaken, it is a done deal.
Sooner or later, you will be made aware of this, that leronlimab is the great immunomodulator. If you understand this now, you have an opportunity to get in very cheap. If you wait until this coming trial proves it, it won't be so cheap.
Posted Dec 17, 2023, 5:49 PM UTC