The Course Of Events & Where They Lead
So, with the recent news that Max Lataillade, DO is both VP at CytoDyn as well as Head of HIV Drug Development at the Gates Foundation, we have a marked change of events. Something has certainly changed now which makes CytoDyn/Leronlimab attractive to Max, attractive to ViiV, and attractive to GSK while it may not have been so attractive it seems, just a short while ago. We could blame it on the Hold that was present then, or was it something else? Because some miracles happened even while leronlimab was on hold, if you remember. Was there some aloof presence that kept CytoDyn alive all along the way?
If you take a look back, some amazing things certainly did happen at CytoDyn that shouldn't have happened. Take Sidley Austin for instance. Nobody can explain how they got here. The $6.5 million bond by David Welch is another. Getting through the lifting of the hold itself was miraculous and so many thanks to Cyrus Arman for his perseverance through that. The hiring of Scott Hansen, PhD with all his knowledge in the CMV vaccine shared with VIR. The hiring of Mitch Cohen. Samsung's agreement to the repayment of the debt owed to them. The amazing HIV breakthroughs of Jonah Sacha, PhD. The Amarex win. Dr. Lalezari's appointment as CEO. The hiring of Melissa Palmer, MD. The hiring of Syneos Health CRO. The hiring of Max Lataillade, DO and on and on it goes. How does any of that happen in such a tiny company that is priced at 11 cents per share? Is it all just a mere coincidence or is there some active force ensuring the advancement of this molecule?
If we take a look back at some of the original problems, Dr. Lalezari mentioned that the "blips" would prevent leronlimab from obtaining monotherapy approval. Dr. Lalezari also brought up the need to address the requirement to develop a longer acting version of leronlimab as well as to exploit the much more complicated side of the act of blocking CCR5, which we all know, ohm20 over at Investor's Hangout, is an expert.
"00:13:30 Dr. Jay Lalezari:
I think another attribute of leronlimab that we don't discuss enough is that it works with once a week dosing. And that's important because for the last five years, I've been looking for a second drug that we might combine leronlimab with in terms of offering patients a competitive once a week treatment regimen that they would be self-administering. And I've had conversations with various of the big HIV pharma companies. They've all sort of universally declined saying that they want a Q-Week regimen to be all oral and that if something's gonna be sub-Q, it needs to be once a month. And so obviously that points to the potential importance of a longer acting analog of leronlimab*, which is actively being pursued. But it is a once a week drug, and if at any point we've been able to come up with another once a week drug, we could have developed leronlimab in HIV, exploiting its antiviral activity, and developing a regimen that would have had considerable commercial appeal." ...*
"00:16:38 Dr. Jay Lalezari:
But the problem is for the second time in the lifetime of this drug, it's kind of gotten lost out in the wilderness like what happened with progenitor. There are obviously three new drugs that have recently been approved with new mechanisms in action, and I think the FDA has rightly indicated that there is really no room for leronlimab in the multi-drug resistant population, that all the needs, there are no unmet needs there. And even though, you know, CDO2 worked, of course it worked, why wouldn't it work? It was very difficult to enroll, but you have an active antiviral added on to an optimized treatment regimen, it's going to work.
But there's no place for it now in the treatment of multi-drug resistant patients. I probably enrolled more of those individuals of the history of the AIDS pandemic than anybody in the world, and they're almost impossible to find now. Again, there is no second drug currently to add to leronlimab, although that might change at some point, at which point potentially exploiting leronlimab as an antiviral with a second agent might be an option, and of course the pursuit of leronlimab with a longer acting version.
And then there was a thought of evaluating leronlimab in the next study as an intensification to existing regimens to reduce blips. And I personally felt that was not a good idea. Miravaroc, which also has about a one and a half log activity, had previously been used as an intensification regimen. It did not reduce blips. And then my experience with leronlimab in the CD03 study, seeing how many patients were blipping, blipping occurs with any immune activation event. So a vaccine, a cold, a herpes outbreak, clinical or subclinical, any sort of illness can turn on the virus.
00:18:43 Dr. Jay Lalezari:
And so I was opposed to betting the barn on an intensification regimen to reduce blips with leronlimab. So no clear fit there. And so we want to move on to what I believe to be true. And now we're shifting from the realm of leronlimab as an antiviral, blocking HIV entry at the receptor site, to the role of leronlimab as inhibiting the biology of CCR5, and specifically as a competitive inhibitor, and in contrast to, I believe, Miravaroc and the other small molecules, which are allosteric inhibitors, leronlimab blocks downstream signaling from various ligands to CCR5.
00:19:34 Dr. Jay Lalezari:
You all are familiar with the literature, CCR5 is popping up everywhere. Stellate cells in the liver are CCR5 positive, and they lay down the fibrosis in the liver. We've all lived through the COVID story with Bruce, and elevated RANTES levels in the ICU patients, and the role of CCR5 in the tumor microenvironment, and this is all much more complicated than simply blocking viral entry.**"
Here is a bit more from the question and answer portion of that Investor Meeting:
"The second part that we get and the question we get frequently about IP is, okay, what's the plan? So something that we're currently excited about internally, and you would have seen disclosures about this, is the third-party generative AI company that we've been working with. In early 2023, we entered into a partnership directed towards developing a long-acting therapeutic, and instead of me talking like an attorney, I'll actually hand it off to Jay here maybe to finish off this concept, but we're very excited about the prospects of a long-acting therapeutic and what it could mean to the marketability of leronlimab as a whole*. So I'll stop, and I don't know, Jay, if you wanted to add anything about the long-acting molecule.*
00:40:38 Dr. Jacob Lalezari:
Well, what I try to paint a picture of is how leronlimab has been wandering in the HIV treatment landscape for two decades, trying to figure out where it fits in, and as a once-a-week therapy, I've had had conversations with Merck and Gilead and VIIV and they uniformly rejected a once a week sub-Q. A feeling that a once a week regimen needed to be all oral, but that once a month sub-Q was acceptable. So if we had or CytoDyn had a longer acting formulation, I think they immediately become competitive in the treatment landscape. Moreover, I think the whole world of PrEP, pre-exposure prophylaxis, with a once a month patient self-administered regimen would be very appealing. So I think having a once a month treatment opens up several doors which are not currently open to CytoDyn.**"
It turned out that leronlimab was very effective at locking up the doorway to the CD4 T-Cell which prevented HIV from entering the CD4 T-cell, but it had no effect on the virus itself. Leronlimab does not kill the HIV virus. Leronlimab was not an anti-viral like other drugs in the ART family. No, leronlimab is a CCR5 blocker and it does that very well. It prevents the HIV virus from entering the cell, so it prevents it from multiplying. However, its half life is only about 10 days, therefore it was injected weekly which was deemed to be too frequent by some HIV drug companies. Also, during a short period of immune suppression, the number of CCR5 receptors on cells increase and subsequently out number the quantity of leronlimab molecules in the treated patient's blood serum, then that leads to available CCR5 for HIV to bind to, which is what happened during the referenced blip type events. But, while these HIV tests were happening, leronlimab was proving itself in other indications and fronts as well, but not as a lock on a door, but rather, in effect, as a blockade of CCR5 itself and what actual good could be accomplished when this particular receptor is blocked.
From the above, it becomes clear that the Big Pharmaceutical companies wanted a long acting HIV drug that was subcutaneously injected. With the hiring of Scott Hansen, PhD, CytoDyn made inroads towards that objective. In addition, Jonah Sacha, PhD, made much more headway towards the Cure of HIV and that certainly is now in the mind set of Max and the Gate's Foundation. Therefore, given that Max has made the recent switch away from ViiV and to CytoDyn and to the Gates Foundation, it tells me that CytoDyn is quite close to having a long acting version of leronlimab. We saw from yesterday's post that Jonah Sacha has a definitive means of Curing HIV in newborns without the use of STEM Cells which is the reason that I believe Max and the Gate's Foundation have decided to fund CytoDyn. But long acting is not involved in this type of HIV Cure. This HIV Cure only requires the use of leronlimab for 8 weeks which would be 8 weekly sub-Q injections, but if there is a 1 month version of leronlimab, then only 2 sub-q long acting injections may be necessary.
Therefore, I believe Max has come to CytoDyn for both HIV Cure and also because of long acting leronlimab. I believe long acting is nearing completion. A lot of what I want to say is written here in Sacha And Hansen Are Up To Something Amazing. There is a collaboration between what Jonah Sacha, PhD and what Scott Hansen, PhD are doing in the quest to find an HIV Cure and to address the PrEP issue. I believe that Max Lataillade, DO along with the Gate's Foundation, also want in on that fight to find the Cure and to exploit the all-inclusive benefits of long acting CCR5 blockade, especially in HIV despite what G is doing. I said this in the previous link:
"I've discussed these 3 fronts through which Jonah Sacha, PhD is seeking to find a cure for certain infectious disease viruses like HIV and Influenza, and really, he doesn't have any competition. We saw yesterday, through 1975BigStocks Post, that VIR is now phasing out their indications in their infectious disease programs, HIV, COVID-19 and Influenza. VIR-1388 and VIR HIV-CURE were T-Cell mediated and they are being phased out.
Seems to me, these companies are realizing that there is no point in trying to compete with CytoDyn when it comes to curing HIV or when it comes to finding a vaccine cure for Influenza. The people at VIR know very well who Jonah Sacha, PhD is, and they who Scott Hansen PhD is and they know these two work in conjunction in pursuit of these goals, that their hands are on the pulse of utilizing the CMV that employs T-Cell meditated vaccinations against certain infectious viruses. They are aware that there is no point in trying to compete with this, especially now since Sacha has proven his concepts. OHSU scientists get closer to developing a universal flu vaccine."
But we have learned that VIR has exited the picture.
"We can see that VIR has recently exited many of their infectious disease indications as a consequence of a partnership they share with Sanofi. They are out of HIV, out of COVID seeing the writing on the wall. Gilead continues to play their silly games biding as much time as they possibly can until that day comes when they can do nothing but bow down to the real cure of HIV. They know that what CytoDyn is doing right now is the real groundwork for an HIV Cure and what they are doing is just keeping people alive on ART. They have relinquished this task of determining an HIV Cure and have passed it off to CytoDyn. They are happy now leronlimab that is not part of keeping HIV+ patients alive, but leronlimab shall re-emerge on this front by means of the prevention and cure of HIV where nobody else has gone before or even desires to do this work*.* They are satisfied allowing CytoDyn to do it via their partnership with OHSU. VIR and Sanofi are phasing out their infectious disease indications thereby making those more available and opportune to CytoDyn. VIR and Sanofi shall use the CMV T-Cell mediated therapy against cancer, tumors and hepatitis, but shall do it without leronlimab or so it seems. CytoDyn pursues these same indications but shall include leronlimab and could also include CMV T-Cell mediated vaccinations as well, I'd say, if Hansen has his way. And where is Hansen these days? Two Steps above Cyrus Arman on the Leadership Board as "Head of Research & Basic Science". For that matter, where is Sacha? Top of the Scientific Advisory Board where he will "Dr. Sacha will lead CytoDyn’s team efforts in HIV PreP and HIV cure.". Time will tell..."
By the way, where does Max Lataillade, DO sit on the CytoDyn leadership board? One step below Dr. Lalezari. Seven steps above Cyrus Arman; Six steps above Joseph Meidling; Five steps above Bernie Cunningham; Four steps above Scott Hansen; Three steps above Dr. Pestell, Two steps above Tyler Blok and One step above Mitch Cohen.
So Max has been ramped up just about to the top of the Leadership Board and with him, he brings the Gate's Foundation. Was it all pre-determined how this would all come together? How did it all work out like this for CytoDyn when so much doom was much more likely? NP did have discussions with the Gate's Foundation, so they were ready then to help fund the way for CytoDyn even without Max. However, given Max's credentials, and their hiring of him to Head their HIV Drug Development, the fact that they were already willing to fund CytoDyn only made the road that much easier for Max, since the Gate's Foundation were already going to fund. But now, the Gate's Foundation gets their own Head of HIV Drug Development to direct and implement their own funding into CytoDyn for their own purposes of HIV Cure and long acting headed up by their own head.
But how do they get around the Blip issue? Enter ViiV and GSK. ViiV supplies their ART drug while GSK supplies their bNAb. Triple therapy is created. Is this our Livimmune? Triple Therapy? The combination of CytoDyn's Leronlimab with ViiR's Cabotegravir ART together with the broadly neutralizing monoclonal antibody VRC07-523LS, an engineered variant of VRC01 that targets the CD4 binding site of the HIV-1 envelope protein owned by GSK. Livimmune could be the combination of these medications in the manner described by Jonah Sacha so as to achieve the HIV Cure.
Now Max is in the center behind all of these companies that constitute the combination therapy Livimmune, which creates the HIV Cure. Yes, he is no longer at ViiV or GSK, but he is very familiar with those integral medications and has familiarized himself with leronlimab just as intimately. Max, together with the Gate's Foundation is entering the fight and is readying his machine. He knows how to fight the battle and come out on top. He has chosen his weapon, and given all his years of experience, his choice is leronlimab, or should I say Livimmune?
Livimmune, if the combination, addresses both the anti-viral effect of the ART and the lock on the door of the CD4 T-Cell using both leronlimab and the bNAb, then Livimmune captures both functions in one combination therapy. This is what Dr. Lalezari was talking about. This is what was necessary to get anywhere with the FDA, plus, it has to be long-acting. So, that's why I'm thinking we are close, especially since Scott Hansen, who is leading the design of long-acting leronlimab, says so himself in May of 2024. 8 months have since passed.
"Scott Hansen 23:41: 17 variants of leronlimab
First and I think Jay concluded his first section of his talk on this is to protect and expand our IP portfolio. We are working with a local generative AI company to design and create not only a longer lasting leronlimab, but possibly a more potent molecule that can be used in pre-exposure prophylaxis or PREP. A space where we think in combination with a long-acting antiretroviral, will have huge impacts for the HIV community.
I'm currently testing 17 new variants of leronlimab. It's really early in this process, but some of these new molecules are showing extreme promise in my in-vitro assays. I'm making sure that the function of leronlimab is not altered, but preserved, and these data are very exciting and yet very, very early, but very promising.
I'm very excited about this endeavor and I feel it will be a game changer for CytoDyn and will help preserve the company's future. Lastly, I feel another game changer for CytoDyn, is the LATCH trial Jay mentioned earlier in his presentation. This is something very exciting for us as a company and me, personally, I became a scientist, not only to move science forward, but to also to try to save life, Dr. Jonah Sasha's work with leronlimab and stem cell transplant in the non-human primate model really made this trial possible for us. He demonstrated that you can pharmacologically knock out CCR5 with leronlimab, essentially creating that Delta 32 phenotype that Jay mentioned. The phenotype has facilitated HIV CURE in the setting of stem cell transplantation.
Obviously, this isn't a therapy for everyone living with HIV, but for those that it makes sense for, we believe leronlimab can help cure people of HIV and that would be pretty remarkable and something we can all be very proud of. I can go on and on about my excitement about this molecule, but for the sake of time, I'm going to hand the mic back over to Jay.
Thank you for listening to me today. It was my pleasure to be here, and I'm happy to be part of all this."
Scott reinforces the need to COMBINE longer lasting leronlimab with a long-acting anti-viral. Is this combination regimen Livimmune? Now, with Max and the Gate's Foundation at arm's length, they are assuming control over this Livimmune combination therapy, under the headship of Dr. Lalezari. Dr. Lalezari in complete control of it all, may take any of the advancements accomplished through the Gate's Foundation and apply those to other indications of which he presides over, like MSS mCRC or mTNBC or MASH.
Max and the Gate's Foundation exploit leronlimab and long acting leronlimab to make it work best for their purposes which are HIV Cure and PrEP. However, the molecule is modified or changed and Dr. Lalezari may use that technology for his benefit in other indications. The relationship is very collaborative, especially since Max works for Dr. Lalezari. GSK and ViiV remain solid players since they are both part of Livimmune as I've defined it here, but GSK becomes more and more involved as Dr. Lalezari makes more and more headway into pertinent indications. VIR has exited the scene, but the knowledge that was garnered by Scott Hansen through VIR, resides now at CytoDyn and is acquired and utilized by Max who is his boss and by Dr. Lalezari who is also his boss. Max made a huge move for a reason and that reason is about to show itself. Most of the infrastructure is already in place. Max does not need first to develop it. It is ready to be utilized.
Keep thinking it through still. As the technology is discovered, both Max and Lalezari use it to their sides of the table. Leronlimab is being developed on both sides. As an anti-viral and as a CCR5 blocker. That explains why Dr. Lalezari pursues the Inflammation - Immune Activation Clinical Trial. He needs to explain how leronlimab functions as an Anti-Viral simply by blocking CCR5. He needs to know that mechanism of action. Yet, Livimmune as Triple Therapy achieves both functions and in doing so, also achieves the cure of HIV and as such achieves FDA approval through Max's efforts.
Nobody has cured HIV. Once this is developed by Max and the Gate's Foundation, G's hands are tied. They are restrained, handcuffed. They can't do anything, locked in, roped in. G is out of the way when this Cure is approved. In one day, they are slammed upside the head. Hamstrung by a rolling stone. This period establishes CytoDyn, when it shall establish control on multiple fronts because of the work headed up today through Max, Gate's Foundation under leadership of Dr. Lalezari.
Posted Dec 8, 2024, 2:43 PM UTC