Looking On Up
The signs have arrived or are arriving. We are definitely in the Season.
CytoDyn is about to capture something sweet that finally matures. Something like a Breakthrough Designation or Right To Try. I recommend we take this possibility quite seriously coming from Flight_19:
"I will add that I believe the abbreviated timeline could be partnership, MOA, and betting there have been discussions with FDA about MOA. My bet is FDA has already advised they would recommend LL for BTD in this indication*."*
Additionally, Ohm says:
"Right to Try is already pretty loose. The doctor, patient and pharma company all agree than the patient gets the drug. I do think that that it should be changed from not only life threatening conditions to also include seriously disabling maladies."
And Jake adds:
"Riz: Great find re CYDY reps listed by ESMO to be present at the poster board in Munich. As you noted, the reps include Dr Jay, Dr Pestell, and 3 other members of the CYDY Leadership Team. (So the PR title was apparently accurate in referencing the Leadership Team traveling to Munich.) Perhaps of even greater potential significance, the reps also include Dr Hope Rugo, who serves on the Scientific Advisory Committee of both CYDY and Gilead, 3 other breast cancer KOLs from prestigious US Medical Schools, and Daniel Adams, the Managing Director of Creatv Micro Tech, the firm that CYDY used to track patients' circulating tumor cells (CTCs) during the 2020-21 mTNBC clinical trial.
You might recall that a few weeks ago I posted a message speculating that the decrease in CTCs referenced in CYDY's 2021 PR regarding info from the trial might be worthy of acceptance by the FDA as a "surrogate endpoint" predicting efficacy as required under its Accelerated Approval provisions. Although I continue to believe that Dr Jay would be more likely to petition the European Medicines Agency for Conditional Marketing Authorization (its version of accelerated approval) under the EMA's broader enabling provisions, I would note that the EMA could also utilize a decrease in CTCs as a predictive efficacy factor favoring approval. Accordingly, including Mr Adams, the CTC guy, in the CYDY traveling party, reinforces my prior speculation that an announcement regarding accelerated approval from either or both the FDA and the EMA might possibly be in play at ESMO*.*
Stay tuned. This story seems to get more interesting by the day."
So, CytoDyn attends The ESMO Conference in Munich, Germany on May 15, 2025 in regards to mTNBC and in addition, they attend The ESMO GI Cancer Conference in Barcelona, Spain on July 4, 2025 in regards to MSS mCRC. This additional GI ESMO conference expands largely CytoDyn's oncologic presence with posters presented at each event. Given its history, CytoDyn likely faces fierce opposition.
CytoDyn's Leadership Team shall be at each conference. They are getting serious now. They plan to discuss the newly discovered MOA in mTNBC, however, the MOA is not only for mTNBC; more than likely, it is applicable throughout all of oncology. Dr. Lalezari introduced it as follows:
"We look forward to sharing details on the progress we have made advancing our clinical development pipeline for leronlimab in oncology,” said Dr. Lalezari. “We are also excited to share information about the apparent mechanism of action in long-term surviving patients that we see as a potentially paradigm-shifting development in solid tumor oncology*.”*
CytoDyn has made its mind up. It shall conquer cancer. Oncology is at the top of their priorities. If one or two other indications need to fall by the way-side so as to win the oncology war, so be it. It is possible we witness CytoDyn give up an indication or two, but win in oncology.
The implementation of their oncologic plans takes place following the discussions planned at ESMO. KC says:
"Okay, great. I've been wondering all along why CYDY would invite KOLs to come to Munchen. Now we see that the FDA sends a representation, the EMA sends one, and the WHO sends one, and that outside meetings are permitted. This could be a chance for CYDY to present, not at the conference as a whole, but to governmental and/or intergovernmental representatives, not to mention reps from other companies. It's very possibly a very influential built-in platform, and not just a poster on a wall for 45 minutes. No wonder Jay, Pestell, and the KOLs are going."
As we have already speculated and do surmise, discussions and meetings concerning oncology have taken place. Could this be why the mCRC trial has not yet begun? Could the standstill be waiting for the Partnership Pact to take it forward? What if the current design of the mCRC trial does not reveal the new MOA well enough? What modifications might be necessary for the Partner to move it forward? Three conferences in the next few weeks to attend and to sign a Pact. The Pact becomes the Chief Cornerstone upon which the whole thing lies.
CytoDyn presents just tiny posters; yeah, Threads of Truth. Not much. These are no ordinary posters but in fact, Power Posters, which represent the Reason for the Season. They contain the details behind the Pacts. The Who, What, Where, When, Why and How behind the Pacts. They punch with power which stems outward from leronlimab as the cancer cure explaining the Why and How behind its MOA. They prove out the new MOA, that such a cure to mTNBC is actually now possible and do point to a similar and expected outcome in mCRC. Ken says something here if true, would be truly amazing:
"Here's what I find important about the new CRC conference poster, at Barcelona.
It's about "Survival." So it's not about the nascent CRC trial. It must be the basket trial.
The basket trial aimed at 30 patients and 22 indications, so the number of CRC patients enrolled had to be very small.
I'm guessing there might have been 3-6 patients with CRC in that basket trial. And the ONLY result that would make this subsection of a tiny five-year-old trial newsworthy enough for a poster display now would have to be this:
MOST OR ALL OF THE CRC PATIENTS IN THE BASKET TRIAL FROM 2021 ARE STILL ALIVE, five years later.
Couple this with the five surviving NBC patients, and you have some amazing results. IMO."
The posters shorten the time frame. Why? Because all of this is happening in the very near future, over the early summer and they are designed for action.
The Pacts must be written properly. There can not be anything which could be damning. That is why the entire Leadership Team goes. They All help to insure the proper alignment of the resulting building. If it is not spelled out precisely, then confusion could result.
For instance, what if the Pact is already in place but the partners wish to run the mCRC clinical trial themselves. u/Upwithstock says if he were the Partnering BP, then he would want to run the trial and not Syneos. However, Syneos is already slated to run it. This is yet another possible explanation as to why the trial is not yet underway? This explains why Cohen and Blok tag along.
The Pact needs to be written rightly, so that the resultant building turns out square. The Clinical Trial NEEDS to draw out the synergistic MOA. Whatever that MOA is, the clinical trial must scream it out so loud that it is clearly appreciated. The Pact must explicitly be built around that new synergistic MOA, not just the one MOA of CCR5 blockade. Whatever oncology clinical trial CytoDyn pursues from now on must purposefully, realistically and outwardly reveal the synergistic MOA. When that is done properly, then CytoDyn comes out on top.
The Top of our company is traveling to ESMO. The Leadership Team. Mitch Cohen. I believe he can write a good contract while Dr. Lalezari absolutely knows what is good for the company. Tyler has his hands on the patents. ESMO therefore, becomes the beginning of a new CytoDyn foundation based on the Plumb Line established by the synergy of two MOAs by which leronlimab creates.
Leronlimab blocks CCR5 and it does something else too.
Let's look at 2 indications: HIV and Cancer.
HIV only requires that leronlimab block CCR5, but Cancer requires both. By blocking CCR5, many of the symptoms which Cancer creates are alleviated, but to gain the long lasting benefit of the Cure, the 2nd MOA is necessary.
I'm thinking MOA #2 has to do with the blockade of another chemokine. Why is MOA #2 necessary? Because MOA #1 doesn't do it alone. It requires MOA #2 to achieve that Vaccine Like Result. So, in order for these two MOAs to synergize with each other, they need to talk to one another. That means they need to speak the same language. Since leronlimab is the one speaking that language, it speaks to CCR5, but it also speaks to CCR2. That means leronlimab also blocks CCR2. So what does blocking CCR2 do?
Was Dr. Chris Recknor onto some other Mechanism of Action that Screamed Succumb No More when he discussed in the 6/30/2022 Conference Call how the CCR5 blockade leronlimab has other profound effects upon other chemokines and could thereby lead to other unknown but wanted effects?:
"28:30 Chris Recknor: 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.
One 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."
and immediately thereafter, Scott Kelly chimes in:
"32:20 Dr. Scott Kelly: Yes, Chris Recknor left with a perfect thing about VCAM b/c we do believe VCAM is important for oncology in leronlimab. What we are doing now, we are currently evaluating opportunities KOM Smithing ford, in mTNBC program for leronlimab in combo with a current SOC as well as colon cancer trial, we have animal and human data for mTNBC as well as animal data on the effects of leronlimab on colon cancer.**"
...
"36:07 Dr. Scott Kelly: 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"
These Ligands Speak the same language that leronlimab speaks such that when leronlimab is present, these Ligands are blocked from speaking to their respective receptors. Leronlimab binds instead to their receptors, and blocks their voice and instead mutes the line. When leronlimab preferentially takes the phone line, and shuts its mouth, the receptor's hearing ear, is asking for a command, but all it receives is a mute line; therefore, leronlimab blocks the functionality of the purpose of that particular ligand, CCL2 in this case. If MOA #2 didn't understand the language of MOA #1, then leronlimab wouldn't be able to accomplish MOA #2. But, since they do speak the same language, it becomes possible for MOA #1 and #2 to work together to achieve these Vaccine Like Results.
Leronlimab has Multiple Mechanisms of Action. All of these are quieted when leronlimab is present.
These are biomarkers which could point to leronlimab's efficacy.
Another possibility about the MOA is the duration that leronlimab was in the body. If the treatment was in place for several months to a year or even two, then possibly sufficient time would elapse in order to permit the immune system to create the proper immune response which creates the patient's immunity to the tumors. We'll find out soon.
Posted May 6, 2025, 9:19 AM UTC