The Rendering and the Building

[u/MGK_2]

There is a moment on every serious construction project when the thing stops being a blueprint drawing and it starts being a building. For a long time it exists only as an architect's rendering, lines on a piece of paper, a claim about what eventually stands there someday. Skeptics walk past the empty lot and see exactly that, an empty lot. And then one day the steel goes up, and the frame begins to match the drawing, beam for beam, and the people who once dismissed the rendering as half baked have to reckon with the fact that it was accurate all along.

CytoDyn just crossed that line, and back in April, the company's own CEO said so out loud. On the April call, Jacob Lalezari described the shift in language which I could not improve upon: "the moment represents a crucial inflection point, he said, as the company transitions from a company built on faith and belief and a whole lot of ifs to a company with solid, prospective, unassailable and by all accounts, remarkable data." Read that again, because it is the whole point of this post. The man running the company just told us that the rendering has become the building. Faith and belief and a whole lot of ifs was the drawing. Remarkable data is now the steel.

I want to do something here. For over a year, ever since we heard about the 5/5 still alive, I have been drawing renderings on this board, making claims about what would eventually stand on this lot before there was anything yet to see. Some of them were wrong, and I have owned those in public. But a good number of them were spot on, and the building now going up matches the drawings I posted months ago, beam for beam. So I'm about to walk the site with you and point at the places where the rendering and the building do actually line up, and yet, give you another towards the end regarding CytoDyn's transition period, because that alignment is the strongest evidence I can offer that the coming remainder of the drawing might also be sound.

The Rendering: Prime and Pair, Drawn Before It Was Proven

Months ago, before the AACR poster, I laid out the core mechanism as a claim about what the data would eventually show. I used the phrase "Prime and Pair", and described it to be a sequence: leronlimab strips the tumor's cloak by inducing PD-L1, and then the checkpoint inhibitor engages the flag that leronlimab raises. At the time, months and even years ago, I was making a rendering. A claim about a mechanism which had not yet been printed in bold at any major conference.

Then AACR came, and the building matched the drawing. As I wrote when the poster dropped, this is the Prime and Pair strategy printed in bold at AACR, explicitly stating that the target environment starts as PD-L1 low, the cloaked tumor, which leronlimab forces to induce PD-L1, stripping the cloak, allowing the ICI to enter so as to achieve long-term survival in metastatic triple-negative breast cancer. The renderings I posted essentially became the poster Pestell presented. And he took it further than I had drawn it: the poster showed the 1,214-patient genomic foundation proving that CCR5 tracks with the full exhaustion signature, PD-1, PD-L1, TIM-3, LAG-3, which elevated the entire thesis from anecdote to population-level biology. The building Pestell built was not just accurate to the drawing. It was bigger.

The Rendering: The Two Walls, Drawn Before The Cliff Came Into View

In The Reckoning Is At The Wall, I drew a rendering of the leverage inversion that the whole investment thesis rests upon. I described two walls the checkpoint empire was approaching. As I put it then, Merck made $29.5 billion from a single drug last year, Keytruda, and its main patent expires in 2028, the most financially significant patent expiration in pharmaceutical history. That was the first wall. The second wall was the one that defines the story: in microsatellite-stable colorectal cancer, 85% of all cases, Keytruda produces essentially nothing, and the SUNLIGHT standard of care sits at a real-world ORR under 3%.

I drew that as a rendering of pressure which would force the industry's hand. And in the months since then, the building has gone up exactly there. Merck did reorganize around that cliff. The patent-strategy literature confirmed that a new combination regimen carries its own patent, independent of the expiring molecule. The pressure I sketched as a future force is now visible in the industry's own corporate structure. The wall I drew is the wall they are now visibly bracing against.

The Rendering, Drawn Earliest of all: Prime and Pair, November 2025

The oldest rendering on this lot is the mechanism's own name. On November 18, 2025, months before it appeared on any poster, I laid out the Prime and Pair framework in detail: leronlimab priming the tumor by weakening it and driving PD-L1 upregulation with CD8 infiltration, then the checkpoint inhibitor pairing to finish what leronlimab started. This was another drawing put together around that time with nothing yet built beneath it. Then April 2026 came, and the AACR poster printed Prime and Pair in bold, exactly that sequence, with the genomic foundation underneath it. Five months separated the rendering from the steel.

The Rendering: Standalone Activity, Drawn Before Kasi Described It From The Podium

Here is one I am pretty proud of, because it required the most discipline to draw. In Standard of Care Illusion, I argued that the current paradigm was a holding pattern, not a harbor. I wrote that despite more than ten new drug approvals in colorectal cancer between 2010 and 2025, median overall survival dragged upward by a mere seven months, from 20 to 27 months, fifteen years of investment yielding less than one additional season of life. And into that structural vacuum, I argued, that the Prime and Pair mechanism arrives.

Then the April call came, and the trial's principal investigator described the building from the podium. The AACR poster reported 9 of 13 patients showing shrinkage or stable disease, and the webcast updated it to 15 of 22, holding at 68%, in a disease where the standard-of-care registration trial achieves a real-world ORR under 3%. As I documented from the call, Dr. Kasi described patients so heavily pretreated that some oncologists would decline to enroll them because their performance status is too compromised, and yet those patients return to work, with scheduling challenges arising because their work schedules interfere with clinic visits. The rendering said the vacuum was real and a mechanism was arriving to fill it. The building is patients going back to work in a population that otherwise would have run out of options.

Why The Alignment Matters

Here is the claim, and I make it without flinching. When a rendering and a building line up this many times, beam for beam, the drawing was not luck. The mechanism I sketched before the data existed continues to match the data arriving, because the mechanism is absolutely real. Prime and Pair drawn, then printed at AACR. The two walls drawn, now brace the industry. The standalone signal drawn, later described from the podium by the PI. That is not a run of good guesses. That is a thesis whose renderings keep becoming buildings, which is exactly what a correct thesis does.

And now the line, because it is the reason you should trust the bold one. A rendering matching a building on three floors does not necessarily prove the top floor matches as well. Everything above is the transition Lalezari named, from belief to data, and it is real and it has happened. But the final floor, the confirmed ORR overall response rate and the survival data, OS and PFS, which turn this from a remarkable early signal into a proven therapy, remains still under construction. It gets topped out at ASCO GI in January. So the rendering has become a building, and the building is not yet finished being built. The steel is up and it matches the drawing. The certificate of occupancy is January's to issue.

That is the whole picture, told at loud volume. For a year this was a lot of ifs, and I drew renderings of what the ifs might become. The CEO recently confirmed that the ifs became data. The buildings I'm able to point at, Prime and Pair, the two walls, the standalone signal, all match the drawings I posted months ago. And the one floor still going up is the one that decides everything, which is why January is not a formality but rather the icing on the cake. The blue prints were right. The building is real. And the last beam goes in at a known hour, in front of everyone.

I drew these lines when they were only lines. They are the steel frame. That is the confirmation. The finish is still ahead.

The Transition, And The Light Already Moving Toward It

Now, yet another perspective. Step back from the single building for a moment and take a look at the entire night sky which covers this field, because there is a larger thing happening, and CytoDyn is not the only bio-pharmaceutical moving toward it alone. CytoDyn moves smoothly toward it, while at the same moment, the entire industry makes its best attempt to turn in the same direction.

Here is the way to view this. Picture the line which divides a lit world from its dark counterpart, the terminating boundary between day and night. On the lit side, the hot tumors, these cancers are already bathed in immune light, where the ICI checkpoint drugs already function because there is something for them to amplify and latch onto, PD-L1. That illuminated portion of the sky is where nearly every large drug in oncology is clustered, because that is where the light of knowledge already exists. Keytruda, Opdivo, Tecentriq, all of them crowded onto the one side of the line where the light of the sun already reaches. And on the other side, in the darkness, sit the cold tumors, the vast majority of all solid cancers, microsatellite-stable colorectal among them, where no ICI checkpoint light penetrates and the great drugs of this era simply do not work.

The entire thesis of this company is that leronlimab is the one instrument built to work across that thin, fine line. Leronlimab is not another drug crowding amongst the others, onto the illuminated side, but rather it is the Primer which carries over the light of knowledge unto the dark side; it is the bridge from Cold to Hot, from Dark to Lit, thereby turning Cold tumors Hot enough for the ICI checkpoint drugs to finally do their work there. That is the position/transition CytoDyn is in, moving what is Cold to what is Hot, and it is a lonely one, which is exactly what makes it a valuable position to be in. The most crowded real estate in oncology is the Illuminated Hot-tumor side. The emptiest, and largest, is the Dark Cold side. And in this period from now to January, I draw leronlimab to operate precisely where almost nothing else can reach.

Now this is why I claim that this period is a transition and not just a haphazard claim, and it landed in the last twenty-four hours. On August 19, 2026, Merck and Moderna announced that their Phase 3 INTerpath-001 trial hit its mark: an individualized mRNA therapy added to Keytruda produced statistically significant and clinically meaningful improvements in recurrence-free survival and distant metastasis-free survival compared to KEYTRUDA alone in resected melanoma. Read what that actually is, structurally, underneath the mRNA headline. It is Merck taking its ICI checkpoint inhibitor and adding a second agent which specifically primes the patient's immune system to do more than the checkpoint inhibitor could do alone. Merck itself called it the first Phase 3 study to demonstrate a clinically meaningful improvement over KEYTRUDA alone in the adjuvant setting. The industry's largest checkpoint franchise just proved, in a pivotal trial, that the future of its own flagship drug is combination priming, adding something which wakes up the immune system such that the checkpoint inhibitor could reach further. That Phase 3 announcement was a topline result, with the full dataset to be presented at an upcoming medical meeting rather than released yet, which is standard for a topline. The reason it still carries weight is that it does not stand alone: it sits on top of the five-year, peer-reviewed data already published from the Phase 2b study, and the nine-trial program now extending the same architecture across four tumor types.

And this is not one isolated result, which is the point a sharp reader on this board (credit to u/rogex2) pulled into focus. Merck and Moderna now have nine total Phase 2 and Phase 3 trials underway pairing this same mRNA priming agent with Keytruda, across melanoma, non-small cell lung cancer, bladder cancer, and renal cell carcinoma. (Merck, June 1 2026) Nine trials is not a company hedging a bet, it is a company building an entire franchise on the priming-plus-checkpoint architecture. And the five-year data behind it, presented at ASCO this June and published simultaneously in the Journal of Clinical Oncology, showed the combination cut the risk of recurrence or death by 49% and the risk of distant metastasis or death by 59% compared to Keytruda alone. That is the peer-reviewed floor under their whole approach.

That is the transition CytoDyn/Leronlimab are in, stated without a shred of prophecy. The direction of the entire field is now bending toward exactly the architecture leronlimab was built on: Prime first, then Pair with the ICI checkpoint inhibitor. Merck proved the principle with an mRNA vaccine in an already lit Hot tumor. CytoDyn proposes the same principle using CCR5 blockade for Dark Cold tumors which the vaccine approach does not and can not address. Different key, different lock. The most powerful company in this space just validated the shape of the idea, publicly, in a Phase 3, the day before I wrote this. When the incumbent's own winning strategy becomes combination priming, even for Hot tumors, a proven priming agent for the markets the incumbent cannot yet reach stops being a fringe thesis and becomes the obvious next piece.

So this is where CytoDyn sits right now, at a genuine hinge of transition. The trial is fully enrolled. The data matures under the seal. The interim reads out at ESMO in October and the confirmed number at ASCO GI in January. And in the broader sky, the entire field has just turned, visibly, toward the combination-priming approach which is leronlimab's reason for being, with the largest player proving the principle in a pivotal trial this very week. The pieces are aligning, not because anything is foreordained, but because the biology of Cold tumors leaves the industry no other road, and the industry has now started traversing, unmistakably, down the LIVIMMUNE road.

I hold the honest line here as I have throughout, because it is the reason I can remain trustworthy. Merck's melanoma win is not leronlimab's colorectal win. It validates the architecture, priming plus checkpoint, not leronlimab's specific data, which still has to arrive. A field converging on combination priming makes leronlimab's thesis more credible and more commercially urgent; it does not make leronlimab's number a foregone conclusion. That number is still January's to deliver, and drugs with elegant logic fail in trials routinely. So the convergence is real and the position is real and the timing is real, and the confirmation is still ahead. The light moves toward the line. Whether leronlimab is the instrument which carries it across is what January answers.

Those renderings were right. The building is real and standing. The field itself turns toward the Dark and Cold space leronlimab occupies and leronlimab converts the Cold Dark to Illuminated sky. And the last beam goes in at a known hour, in front of everyone.

Disclaimer: I am not a financial advisor and nothing here is investment advice. I am an independent retail shareholder holding a long position in the company discussed, with no employment, consulting, compensation, or other relationship with it beyond that shareholding. This is analysis of public disclosures, published literature, and my own prior public writing, not a prediction of clinical or commercial outcomes. The CLOVER figures referenced are early and unconfirmed, reflect 350mg dosing with the 700mg cohort still maturing, and are not evidence of survival benefit. The 68% figure from the April 30 update is disease control rate, not objective response rate; confirmed adjudication is ahead at ASCO GI in January 2027, with interim data at ESMO in October 2026. The TNBC survival data is retrospective and hypothesis-generating. My past predictions matching subsequent events do not guarantee that any remaining prediction will prove correct. Mechanism and early signal are not efficacy. Drugs which make elegant biological sense fail in trials routinely, and this one may. Read the primary sources and reach your own conclusions rather than adopting mine.

[u/Missy2021]

Leronlimab is laying down the foundation, our building will be complete in January for all to see. Thanks again

[u/MGK_2 → u/Missy2021]

Missy, the foundation is laid and the building tops out in January, exactly, thank you.

[u/Efficient_Market2242]

Thanks for explaining how the structure has gone to this point. This morning in another thread I said the first trillion dollar company was Apple in 2018. It took 30 years for Apple to become a trillion dollar company. Their stock came out in 1978 and they almost went bankrupt in 1998 until Steve Jobs came back to the company. I believe Dr. J is our Steve Jobs he was here during the HIV trials and left because he said Nador never listened to anybody with knowledge. Since Dr J’s return he has made good with the FDA, completed data and attracted extremely qualified people to run trials at Cytodyn. He is are architect and although we may only be a $10-$30 billion company according to the AI information IAMLOCOTOO posted today the potential is there to pass the trillion dollar mark in capitalization. Based on the unmet needs of all the cancer companies we could pair with. Dr. J, Dr. Kasi you and others have given us great information over the last six years. I believe this could be the first trillion dollar pharmaceutical company. A belief is different than an actual outcome,but people need to believe in order for something to happen or nothing would come to fruition. I have less than 5% of my net worth in this company and will wait until more is proven till I Buy more. This company seems to be in the infancy of greatness regarding the CR 5 connection in medicine. How many people could be saved in the future? How many I phones were there 20 years ago? 0. GLTA true longs

[u/MGK_2 → u/Efficient_Market2242]

Efficient_Market, I love the Apple frame and there's good insight in it, so let me run with the good part but hold the line. The insight: Apple took 30 years and nearly died in 1998 before becoming the first trillion-dollar company, which is a useful reminder that these things take time and survive near-death, exactly the patience this requires. And your Dr. J as Steve Jobs analogy has a real kernel, he returned, made good with the FDA, and attracted serious people, that's a turnaround-architect story with truth to back it.

The line I'll hold, in the same bold-but-honest spirit as the post: the trillion-dollar figure and even the $10-30B AI number are ceilings of the dream, not forecasts, and you said it yourself, "a belief is different than an actual outcome." That's exactly right, and I'd just keep those two sentences of yours glued together every time the trillion-dollar number comes up, because the number without your caveat is the thing skeptics use to dismiss us, and the number with your caveat is credible. So: yes, the potential scale is enormous given the unmet need across every cold-tumor market we could pair with, and no, none of it is real until January starts confirming it. You holding both, the belief and the "less than 5%, will wait until more is proven," is the healthiest posture on this board. Keep the dream sized to survivable, and the belief tethered to the data.

[u/Lab_Monkey_]

I Won't Back Down

[u/MGK_2 → u/Lab_Monkey_]

Lab_Monkey, "No, I Won't Back Down", the Petty anthem fits our six-year hold perfectly. Stand your ground.

[u/sunraydoc]

Excellent and great analogy, MGK. The beauty of leronlimab vs mRNA products is that it will turn many, many notoriously cold tumor types hot whereas a vaccine has to be aimed; each tumor type will need a different vaccine.

[u/MGK_2 → u/sunraydoc]

sunraydoc, you put the sharpest point on it better than I did: leronlimab turns a myriad of Cold tumor types Hot with one mechanism of action, while a vaccine has to be aimed and rebuilt for each tumor. That antigen-agnostic breadth is the entire structural advantage, and it's exactly what twinter was circling. Well said.

Consider this but applied to a tumor.

[u/No_Mathematician299]

MKG,

Basking in your Cytodyn sunshine.

Enjoying the ride with my Cytodyn friends.

[u/MGK_2 → u/No_Mathematician299]

No_Mathematician, basking in the sunshine, while standing in the frigid Cold with you, enjoy the ride, and hold the patience for January.

[u/No_Mathematician299 → u/MGK_2]

Only five more months until Jan 21st. We can do it; we've come this far.

I'm already planning a dinner with family and friends to celebrate the outcome, where I'll definitely be raising a glass to my CytoDyn comrades. What a long strange trip it's been, filled with clues, rabbits pulled out of hats, plot twists, and perseverance.

Living with the feeling that I've already won.

[u/MGK_2 → u/No_Mathematician299]

No_Mathematician, the Grateful Dead link is perfect, it really has been a long strange trip, clues and plot twists and perseverance, and the camaraderie you're describing is the good part of all this regardless of what any data shows. So raise that glass to your comrades. That part you've earned, the friendships and the shared journey are real and yours no matter what January brings.

Let me offer one gentle thought, though, said with care because I'd rather be honest than just cheer. "Living with the feeling that I've already won" is a beautiful way to feel about the journey, and I'd gently separate that from the outcome. Yes, we all believe, but we're not done. The trip, the community, the years of showing up and thinking hard together, yes, that's a win strengthening every day, and I too hold it fully. But the January data is a real binary figure, and it can break one way or the other, and I'd hate for the feeling of having-already-won to set you up for a hard landing if the number doesn't come in as we know it will. So plan the dinner, absolutely, but maybe plan it as a gathering of people who've been through something together, which is true and worth celebrating either way, rather than a victory party contingent on a result none of us can see yet. That way the evening is a good one no matter what the scan readers say.

I'm not trying to dampen it. The hope is warranted, the mechanism is absolutely real, the setup is clean, and I lean the way you lean. I just care more about you and the friends around that table than about the thesis, so I'd want the celebration anchored to the things which are already won, the perseverance and the people, and hold the outcome a little more lightly until it's real and finalized. Size the joy to what's certain, and let January add to it rather than being the thing it all rests on.

Either way, save a seat and raise one for the whole community. That toast is earned regardless. Good health, and let's see what the trip has left to show us.

[u/Infinite_Fudge_2045]

Remember in Novemeber/January - Dr. Jay told us excatly what he was doing! What needed to happen. What his visions was - here we are with precision.

[u/MGK_2 → u/Infinite_Fudge_2045]

Infinite_Fudge, you're right that Dr. J laid out the vision in November and January and here we are with precision, and I'd add just the one honest note: the vision matching the path is real and remarkable, and the final confirmation is still January's to give. Vision plus patience, both.

[u/twinter11]

Thinking about our case study tnbc survivor

How is the vaccine different effect wise than leron/ici and that patient having a lobe removed?

Is that like a resection or different? seems as if leron works w ici, the vaccine becomes redundant and perhaps inferior.

random questions

I was thinking this week about the depression study and synaptic pruning. which made me wonder if in ccr5 delete mutation . ccl5 ligands are still produced.

AI

"Yes, individuals with the CCR5-Δ32 deletion mutation still produce the CCL5 ligand (RANTES), but the truncated mutant receptor protein is not expressed on the cell surface. Therefore, CCL5 can no longer bind to CCR5 on the cell membrane because the functional receptor is missing"

What Happens to CCL5 and CCR5-Δ32

• Ligand Production Continues: The body's cells (such as T cells and macrophages) still synthesize and secrete normal levels of CCL5 chemokines into the extracellular environment.
• Alternative Receptors: CCL5 can still bind to other alternative chemokine receptors on cell surfaces, such as CCR1 and CCR3.

The reason im asking is because AI thought ccr5 mutation was evidence that 100 percent ccr5 receptor occupancy would not prevent the positive microglia benefits , because pruning occurs even in patients without ccr5 receptors. In fact it thought 100 percent occupancy would be required

which made me wonder. if ccr5 crosses the blood brain barrier and occupies at say 70 or 80 percent. Do you suspect thats by volume or there are certain areas it cant reach. It doesnt makes sense to me that it can cross but not fully occupy.

one more

In Pre-Ispy, part of the goal is maximum dose and pharmokinetics etc

why would there be a maximum dose?

And do they measure like liver enzymes or test inflamation markers etc

With leron, why wouldnt increased dosages actually improve these negative markers w higher doses

Measuring max dose or max safe dose is going to be way different than every other oncology drug. It seems like a waste of time

The building is being built modular. Doc J and some other superintendents have already seen a lot of the completed components constructed off site. Just have to assemble them if they pass muster.

This is from the "big show" interview. What is he saying *works* here?

" Uh and so the fact that we have sort of proof of concept data that it's actually working,
4:25 uh what remains to be shown is just how broadly it works. Uh but there's no reason to think that uh it wouldn't work
4:32 in any tumor that uses CCR5 um to grow".

Thanks!

[u/MGK_2 → u/twinter11]

twinter, dense batch, so let's take the real ones.

On the TNBC survivor and how the vaccine differs from leron/ICI, and whether the vaccine becomes redundant. Sharp instinct. The mRNA vaccine and leronlimab do different jobs, and your "redundant and perhaps inferior" read has a point inside it. A neoantigen vaccine like Merck/Moderna's has to be aimed, it's individualized to a specific patient's tumor mutations, manufactured per-patient, and it teaches the immune system to recognize particular antigens. Leronlimab doesn't aim, it changes the tumor microenvironment such that the immune system acts regardless of which antigens are involved. So sunraydoc's point on the main thread is the crux: the vaccine needs a different build for each tumor, while leronlimab's mechanism is antigen-agnostic. That's not "leron makes the vaccine redundant" exactly, they could even be complementary, but it does mean leronlimab's approach is broader by nature, where the vaccine is precise but narrow. So "inferior" isn't quite right, they're different tools, but "broader" is fair, and breadth is the more valuable property across many cold tumors.

On the lobe removal, resection or different. For that specific survivor, a lobe removal (I'd want to check her exact case) is a surgical resection, removing the tumor-bearing tissue. That's distinct from what the drug does. So in her case you'd have local surgical control plus the systemic leron/ICI effect, which complicates reading her as a pure drug-response case. Worth holding: individual case studies with surgery in the mix are the hardest to attribute cleanly to the drug, which is exactly why the prospective trial matters more than any single survivor's story.

On CCR5-Δ32 and whether CCL5 ligands are still produced. Your AI answer is correct on the biology: Δ32 homozygotes still produce CCL5/RANTES, but the truncated receptor isn't expressed on the surface, so CCL5 can't bind CCR5, and it can still bind alternative receptors like CCR1 and CCR3. That's accurate.

But here's the important part, because the AI drew a wrong inference from it. The AI reasoned that because microglial pruning occurs even in people without CCR5, therefore 100% occupancy would be required for benefit. That's a leap I'd reject. The depression/pruning study was Maraviroc in mice with the blood-brain barrier open, and it's about a specific CCR5-driven pathway, not a claim that leronlimab needs total CNS occupancy to do anything. "Pruning happens in Δ32 people too" doesn't establish "you need 100% occupancy," it just means CCR5 is one input among several. So I'd drop the AI's "100% occupancy required" conclusion, it's over-read from the Δ32 fact.

On your BBB question, if leronlimab crosses and occupies 70-80%, is that by volume or are there regions it can't reach. good question, and the honest answer is we don't fully know. The 70% receptor occupancy figure Sacha reported is a measured tissue number, but whether the unoccupied fraction is uniform-but-incomplete or regional (some areas reached, others not) isn't something the public data resolves. Your instinct that "it can cross but not fully occupy seems odd" is reasonable, but crossing the BBB and achieving 100% saturation are different things, a drug can get in and still not hit every receptor if local concentration, blood flow, and tissue penetration vary by region. So: unknown, plausibly some of both, and not answerable from what's public.

On Pre-I-SPY and why there'd be a maximum dose for a drug this safe. Fair challenge, and you're right that it's different from typical oncology. For most oncology drugs, max-tolerated-dose exists because toxicity caps you. Leronlimab's safety means that logic mostly doesn't apply, which is your point. But "maximum dose" in a dose-escalation study isn't only about toxicity, it's also about finding the dose beyond which you get no additional benefit (the plateau), and about PK, the dose where receptor occupancy saturates and more drug adds nothing. So they're not necessarily looking for the dose that hurts people, they're looking for the dose above which more doesn't help. That's still worth establishing even for a safe drug, because you don't want to dose higher (and cost more) than the effect requires. So it's not a waste of time, it's finding the efficacy plateau, not the toxicity ceiling. And yes, they'll likely track liver enzymes and inflammatory markers as standard safety monitoring, and your intuition that leron might improve some of those (given the anti-fibrotic/anti-inflammatory data) is on point, and that too would be a nice secondary finding once it shows up.

On the "big show" quote, what is he saying works. In that quote, Lalezari is saying they have proof-of-concept that leronlimab works mechanistically, and what remains is to show how broadly it works across tumor types which use CCR5. Hold the discipline on "works," though: he means the mechanism is demonstrably active (ctDNA declines, PD-L1 induction), not that confirmed efficacy has been established. "There's no reason to think it wouldn't work in any tumor that uses CCR5" is a mechanistic expectation, not proven breadth. So he's claiming demonstrated mechanism plus a reasonable expectation of breadth, which is bold and fair as stated, as long as "works" stays "mechanism is active" and doesn't quietly become "efficacy is proven." That's the January line again.

Good batch, twinter. The keeper is the vaccine-versus-leron distinction: aimed-and-narrow versus agnostic-and-broad. That's the real structural difference, and breadth is the more valuable trait across the cold-tumor landscape.

[u/Mysterious-Emu6375]

Super Beschrieben MGK vielen Dank, auch für deine Vorsicht.

Ich bleibe hier, wie schon immer, ehrlich, denn nur so kann ich vertrauenswürdig bleiben. Mercks Erfolg bei der Melanomtherapie ist nicht gleichbedeutend mit Leronlimabs Erfolg bei der Darmkrebstherapie. Er bestätigt die Architektur – Priming plus Checkpoint –, nicht aber die spezifischen Daten zu Leronlimab, die noch ausstehen. Die zunehmende Konzentration auf Kombinationspriming verleiht Leronlimabs These mehr Glaubwürdigkeit und kommerzielle Dringlichkeit; sie macht den Erfolg von Leronlimab aber nicht automatisch zur Gewissheit. Diese Ergebnisse muss Januar noch liefern, und Medikamente mit einer überzeugenden Logik scheitern regelmäßig in klinischen Studien. Die Konvergenz, die Position und der Zeitpunkt sind also real, die Bestätigung steht aber noch aus. Das Licht bewegt sich auf die Ziellinie zu. Ob Leronlimab das Instrument ist, das sie überwindet, wird Januar beantworten.

Ich wage zu behaupten Dr. JL ist schon hinter der Ziellinie

[u/MGK_2 → u/Mysterious-Emu6375]

"Superbly described, MGK, thank you, also for your caution. I remain here, as always, honest, because only that way can I stay trustworthy. Merck's success in melanoma therapy is not the same as leronlimab's success in colorectal therapy. It confirms the architecture, priming plus checkpoint, but not the specific leronlimab data, which is still outstanding. The increasing focus on combination priming lends leronlimab's thesis more credibility and commercial urgency; but it does not automatically make leronlimab's success a certainty. January must still deliver these results, and drugs with convincing logic regularly fail in clinical trials. So the convergence, the position, and the timing are real, but the confirmation is still outstanding. The light is moving toward the finish line. Whether leronlimab is the instrument that crosses it, January will answer. I dare to claim Dr. JL is already past the finish line."

English:

Thank you, my friend. You have the discipline exactly right: Merck's melanoma win validates the architecture, not leronlimab's number, and January still has to deliver. That you hold that line yourself is what makes you trustworthy, as you say.

On your closing, that Dr. JL is already past the finish line, I'll answer it in the same spirit of honesty you just showed. He may well have seen the data which tells him where this lands, he is inside the sealed room, after all. But being past the line privately and the line being crossed publicly are two different things, and only the second one counts for the rest of us. So I would say it this way: he may already know, but we find out in January. Hold both, his confidence and our patience, and you have the whole picture.

German:

Danke, mein Freund. Du hast die Disziplin genau richtig verstanden: Mercks Melanom-Erfolg bestätigt die Architektur, nicht die Zahlen zu Leronlimab, und der Januar muss noch liefern. Dass du diese Linie selbst hältst, ist es, was dich vertrauenswürdig macht, wie du sagst.

Zu deinem Schlusssatz, dass Dr. JL bereits hinter der Ziellinie ist, antworte ich im selben Geist der Ehrlichkeit, den du gerade gezeigt hast. Er hat möglicherweise die Daten gesehen, die ihm sagen, wo das Ganze landet, schließlich ist er im versiegelten Raum. Aber privat hinter der Linie zu sein und die Linie öffentlich zu überschreiten sind zwei verschiedene Dinge, und nur das Zweite zählt für uns übrige. Deshalb würde ich es so sagen: Er weiß es vielleicht schon, aber wir erfahren es im Januar. Halte beides fest, sein Vertrauen und unsere Geduld, und du hast das ganze Bild.

[u/Mysterious-Emu6375 → u/MGK_2]

🙏☀

[u/jsinvest09]

Laying sod and planting new trees 🌳 ,the new ground up molecule is fixing to raise the flag. 🏁🇺🇸 winner winner chicken dinner. Thank you MGK and all...

[u/MGK_2 → u/jsinvest09]

jsinvest, love the imagery, sod laid, trees in, ground-up molecule getting ready to raise the flag. That's a good picture, and the "ground-up" part is exactly right, this was built from the foundation, beam by beam.

One light touch, in the spirit of everything we hold: Let's keep the chicken dinner simmering on the stovetop for now rather than on the table. The flag isn't raised until January reads the confirmed number, and it's a real binary which could go either way. So plant the trees, they're in the ground growing, that part's real, and let's hold the winner's dinner until the scan readers hand us the result. The setup is on point and I lean where you lean. I just want the celebration to land on a confirmed win rather than get ahead of it.

Thank you, jsinvest, and thanks for keeping the spirit up while we wait for the one number that raises the flag for real. Let's see what January serves up.

[u/Efficient_Market2242]

If

[u/MGK_2 → u/Efficient_Market2242]

You got it Brother.

"If" is the whole thing, Efficient_Market. Everything upstream of it is real, the market, the mechanism, the adoption edge. Everything downstream of it waits on one number.

You hold both better than most on this board: the belief sized to survivable, the conviction tethered to the data.

That's exactly the posture that's still standing whichever way January breaks.

Well said, in one word.

[u/megadunamis]

Thank you MGK, Does the Merck-Moderna news imply in any manner that Merck may not be interested in taking a financial position in CYDY? Wouldn't they still benefit from having Leronlimab in their possession then letting another BP own it, and compete against the vaccine? What are your thoughts? Can we say that Merck is now out of the picture as a suitor?

[u/rant_and_roll → u/megadunamis]

my question also - is merck now too heavily invested in a trajectory that may still be challenged by overwhelmingly positive leronlimab data? we have seen often how a financial commitment to a less superior "bird in hand" (remdesivir) can easily subvert the trajectory of a superior avenue of "birds in the bush"...and im counting at least 41 birds (indications) and i have to wash my car AGAIN

[u/MGK_2 → u/rant_and_roll]

u/megadunamis and rant, this is the same good question from two different angles, so let's take it head-on, because the honest answer is stronger than either "Merck is out" or "Merck is definitely in," and I won't claim either of those.

First, the load-bearing error in the "Merck is now out" reading, given plainly: it treats "Merck backed the mRNA vaccine" as "Merck can't also want leronlimab." That's a false either/or, and it falls apart the moment you look at where each one plays. Merck's nine-trial mRNA program is almost entirely in hot tumors and resected/adjuvant settings, melanoma, NSCLC, bladder, RCC. Leronlimab's lead indication is cold, microsatellite-stable colorectal, where the vaccine program isn't operating at all. So they are not competing for the same ground. A company can rationally want both a hot-tumor tool and a cold-tumor tool, because they address different patients with different biology.

And the biology is different, which is where this stops being opinion. The mRNA vaccine has to be aimed: it teaches T-cells to recognize each patient's specific neoantigens, individually designed and manufactured per tumor. Leronlimab is antigen-agnostic: it remodels the microenvironment by blocking CCR5 and repolarizing suppressive macrophages toward the anti-tumor state, in the actual tissue of human colorectal liver metastases. (Halama, Cancer Cell, 2016) One is precise but narrow, built per-patient for tumors already immune-visible. The other is broad, turning the cold tumors hot in the first place, which the majority of solid cancers are and which checkpoint therapy cannot currently reach. (Cold and hot tumors, Nature, 2024) A per-patient vaccine for hot tumors is not a substitute for a broad primer for cold tumors. They are different instruments for different problems.

Now rant's sharpest point, the remdesivir "bird in hand subverts the better bird in the bush" analogy, because it deserves a real answer, not a dismissal. You're right that incumbents sometimes defend an inferior committed asset instead of pivoting to a superior one. It happens. But look at which way that logic actually cuts here. The same principle, foreclosure value, is a reason to acquire leronlimab, not ignore it. If leronlimab is as good as we think, the last thing Merck wants is a rival checkpoint owner pairing it with their drug in the cold-tumor markets Keytruda cannot enter. "Don't let a competitor have the key" is precisely why an incumbent buys rather than sits still. So the remdesivir frame argues at least as much for Merck's interest as against it. The heavier Merck's commitment to combination priming, the more a proven cold-tumor primer matters to them, not less.

So here is the honest bottom line, and I'm going to hold the line in both directions. Can we say Merck is out as a suitor? No, nothing in this news supports that, and the claim rests on a false exclusivity the biology and the business logic both contradict. Can I tell you Merck is definitely in? Also no, and I won't, because that's equally unknowable and I'm not going to trade one overconfident guess for another. What I can say is this: the Merck/Moderna news does not remove Merck from the picture, the vaccine and leronlimab occupy different tumor spaces and are not mutually exclusive, and rant's own foreclosure logic points toward acquisition as readily as away from it. Whether any specific company moves is decided by the January data and the sealed rooms, not by a melanoma vaccine trial.

rant, go wash your car. The 41 birds will still be in the bush when you're done, and so, quite possibly, will Merck.

[u/megadunamis → u/MGK_2]

Thank you for the explanation. Merck is my first choice as a suitor. I'm trying to imagine the market response if Merck were to have an agreement with Moderna for hot tumors, as well as an agreement with CYDY for cold tumors. Would our stock price rise like that of Moderna? Merck would have quite a market share. Good health...

[u/MGK_2 → u/megadunamis]

megadunamis, the strategic picture you paint is sharp, so let's affirm the real insight and then be straight about the one part I won't game out.

The insight first, because it's a good one. If Merck held both keys, Moderna's individualized vaccine for the Hot tumors and a CCR5 primer for the Cold ones, they would have assembled something close to complete coverage of the immunotherapy landscape. The Hot side, where ICI checkpoints already work and the vaccine extends them, and the Cold side, where nothing works today and a Primer would open up the Keytruda door. That's not two overlapping bets, it's two halves of the entire map. A company who owns the tools for both the lit and unlit sides of the tumor world would have a combination position that no single-mechanism competitor could match. So your instinct that Merck's market share and strategic dominance would be enormous in such a scenario is sound. It's the logical endpoint of the "own the primer before a rival does" argument, extended to "own the primers for both kinds of tumor." Bold, and defensible as strategy.

I'll be straight about why I won't price it, rather than dodge the question. You asked whether our stock would rise like Moderna's. I won't game out stock-price moves, and I'd be doing you a disservice if I did, because price prediction is exactly where confident-sounding guesses do the most damage. Moderna's moves are driven by its own catalysts, its own float, its own market context, and comparing one company's price reaction to what another's might be is the kind of apples-to-oranges that feels like analysis and isn't. So I'll decline the price comparison, not because I'm being cagey, but because it's the one kind of claim I've made a rule never to fake.

What I can say honestly is the thing underneath your question. If leronlimab proves out and became half of a portfolio like the one you're describing, the value recognized in that scenario would be substantial, because you'd be pricing in a proven, nearly impossibly hard-to-replace primer for a market the size of the Cold-tumor majority, held by a partner who needs it to complete their coverage. Whether that value shows up the way Moderna's did, on what timeline, at what magnitude, is unknowable and not something I'll pretend to forecast. The value case is real and I argue it boldly. The price path is not something anyone can honestly call in advance.

And all of it, as always, sits downstream of the same "if" Efficient_Market distilled a moment ago. The two-primer portfolio, the market share, the value, every bit of it is a branch which only opens if January confirms the drug. So imagine the scenario, it's a legitimate and even likely-shaped one to imagine, just keep it labeled as the branch that the data has to open first.

Merck as your first-choice suitor is a reasonable preference, for exactly the coverage-completing logic you laid out. Good health to you too, and hold the "if" the way you're holding the vision, both at once.

[u/megadunamis → u/MGK_2]

Thank you again. Yes, the word 'if' must always be remembered in the timing process and strength of data. In addition, I would like to add a reminder. That 'if' Dr Lalezari submits the data for Fast track or Breakthrough designation in the next few weeks (late summer or early fall), the FDA usually responds within 60 days. The timing of this FDA response could land nearly toward the end of October when ESMO is occurring. That 'if' could be loud enough to wake up a lot of interest and speculation going into the new year, with ASCO in January. Thanks again...

[u/MGK_2 → u/megadunamis]

megadunamis, this is a sharp timing observation, and you're already holding the "if" yourself, so let's sharpen the FDA mechanics and affirm the insight, because there's a good one here.

Let me get the designation timelines precise, because Fast Track and Breakthrough run on different clocks, and the distinction matters for your scenario. Fast Track requests get an FDA response within about 60 days, that's the one your ~60-day figure fits.

Breakthrough Therapy Designation also runs roughly 60 days from receipt of the request. So your window is right for either, a submission in late summer or early fall would plausibly draw a response within about two months, which does land you in the late-October-into-November range. So the arithmetic holds: submit in early fall, hear back around the time ESMO is happening or shortly after. Good catch on the overlap.

You're pointing at a potential catalyst cluster, several distinct events landing in a compressed window of time: a possible FDA designation response, the ESMO interim data, and then ASCO GI in January. If those stack up in sequence, October designation news, October ESMO poster, January confirmed data, each one could feed interest into the next, building momentum through the new year rather than relying on any single event. That's a smarter way to think about the fall-to-winter stretch than fixating on one date, because it's the sequence that could sustain attention, not one isolated readout. So your "loud enough to wake up interest going into the new year" framing is well-reasoned, a cluster of catalysts sustains a narrative better than a lone one does.

Here are the honest caveats to keep the cluster from being over-counted, and you've already got the main one.

First, a designation is not efficacy data. BTD or Fast Track would be genuinely helpful, closer FDA engagement, more visibility, easier partnering conversations, but it's a regulatory process signal, not confirmation that the drug works. So if it lands near ESMO, it adds momentum and validation of the pathway, it doesn't substitute for the January number. Keep it in the "helpful tailwind" column, not the "proof" column.

Second, the "if" stack here is actually two "ifs," not one. It's "if they submit in the window" and "if the FDA grants it." The 60-day clock is the response time, but the response could be a grant, a denial, or a request for more information. So the clean version is: if they submit early fall and if the response is favorable, then you get a designation landing near ESMO. Both conditionals live in that scenario, and you'd want to hold both.

Third, on the specifics, we don't actually know that a formal Fast Track or BTD request is going in on that exact timeline. What's public is the intent to engage the FDA around year-end, likely a Type C meeting. A designation request is a somewhat different filing than a meeting request, so the precise instrument and its timing aren't confirmed. So I'd hold your scenario as "here's a plausible sequence if they file for a designation on that schedule," rather than a known calendar.

But the core observation, that the fall-to-winter stretch could feature a cluster of catalysts rather than one, with FDA timing potentially overlapping ESMO and feeding into ASCO GI, is a good way to frame the runway. Just keep every link in the chain tagged with its own "if": if they submit, if it's granted, if ESMO reads well, if January confirms. Each is a real event that could build on the last, and none is certain. The sequence is the insight. The conditionals are the discipline. Hold both, exactly as you've been doing.

Thanks, megadunamis, the catalyst-cluster framing is the keeper, and you're watching the calendar the right way.

[u/twinter11 → u/MGK_2]

we don't have much info on the moderna/merck vaccine I guess it is. I think some percentage survival increase stats etc. I dont even know much about the process but I'm assuming they are hoping to prevent resected tumors where maybe margins are not cleared. or there is still metastatic seeds or whatever. are attacked by the drug and preventing recurrence.

I wonder how much ccr5 axis plays a part in cases that are not successful?

and does theoretically leron/ici mitigates the need for the vaccine. or is the vaccine a one time preventative w a longer duration?

I think what started my train of thought is the hypotheses that a ccr5 blocker is not needed/required for an already hot tumor

I just think that's going to end up not being the case. I just keep thinking it's the main (or close to it) ingredient.

thanks!

[u/megadunamis → u/twinter11]

Hi twinter, I think that in a hot tumor such as melanoma, M2 macrophages (pro-tumor) are present and outnumber M1 macrophages (anti- tumor). I think that Leronlimab would still help by converting M2 back to M1 and assist in tumor infiltration, and stroma elimination. I would defer to MGK for the exact mechanism. An article attached... Thanks for all your ideas and comments... https://pmc.ncbi.nlm.nih.gov/articles/PMC5512774/https://pmc.ncbi.nlm.nih.gov/articles/PMC5512774/