Asteroid Approaching

K, let's get right to the point.

CytoDyn Engages Syneos Health as CRO for its Phase II was sent out towards end of week. I'm sure you all read it by now but I include it here for completeness:

"VANCOUVER, Washington, Oct. 04, 2024 (GLOBE NEWSWIRE) -- CytoDyn Inc. (OTCQB: CYDY) ("CytoDyn" or the "Company"), a biotechnology company developing leronlimab, a CCR5 antagonist with the potential for multiple therapeutic indications, announced today that it has engaged Syneos Health as the contract research organization (“CRO”) for its upcoming Phase II oncology trial. The trial will evaluate the efficacy of leronlimab in patients with relapsed/refractory micro-satellite stable colorectal cancer (“CRC”).

Syneos Health is a leading fully integrated biopharmaceutical solutions organization that supports customers in accelerating the delivery of life-saving therapies to market. Syneos Health leverages advanced data analytics and AI/ML capabilities to improve outcomes at every stage of the asset lifecycle, from clinical development to commercialization. Syneos Health has helped to develop or commercialize 92% of novel new drugs approved by the FDA in the last five years (2019-2023) and 91% of products granted marketing authorization by the European Medicines Agency.

“Investigating leronlimab in the field of oncology remains our top priority, and we are excited to further invest in our promising relationship with Syneos Health. With this expanded mandate, we expect to generate clinical data affirming the utility of leronlimab in combination with trifluridine plus tipiracil (TAS-102) and bevacizumab,” said Dr. Jacob Lalezari, CEO.

As previously announced, the Company’s final study protocol was submitted to the FDA for approval in September 2024, and CytoDyn expects to start screening patients in early 2025."

This particular CRO was already announced as the CRO for the Inflammation Trial. Now also for the MSS mCRC trial too. Syneos Health is a Top of the line CRO. as per Bio4. What was the reaction to the Press Release? A short attack preventing share price from escalating. The only way they have to attack CytoDyn is the very thing they are employing. But, it isn't stopping CytoDyn. Despite their thumb on our heads, CytoDyn remains in control, doing what it has set out to do.

This press release is pretty massive. Not just because of who the CRO is, but again because of the indication. MSS mCRC is massive indication, because it is a CCR5 dependent cancer. In addition, we already know from previous studies that MSS mCRC is at least modestly susceptible to VEGF inhibition and VEGF inhibition is dependent upon the CCR5/CCL5 axis. Extrapolating, this means that MSS mCRC proliferation is dependent upon the CCR5/CCL5 axis. If this CCR5/CCL5 axis is intact, MSS mCRC can proliferate, if this axis is blocked say by leronlimab, MSS mCRC would suffocate for lack of nutrient blood supply and lack of oxygen which that blood supply would bring to the tumor.

MSS mCRC currently is an un-treatable cancer, as chemotherapy is the only approved treatment which has an ORR of 6.1%, (Overall Response Rate). The combination trial proposed by CytoDyn that includes leronlimab shall make MSS mCRC that much more treatable than it currently is; I'm predicting an ORR in excess of 33-45% or at least 6-9 times better than current SOC.

The quote immediately below pertains to the fact that VEGF formation is greatly dependent upon the CCR5/CCL5 axis. VEGF formation only happens when the CCR5/CCL5 axis is working. When VEGF is inhibited with bevacizumab/Avastin, both MSI and MSS ColoRectal Cancers are best controlled and suppressed.

"Some excellent p values too: Among the evaluation and control cohorts, patients with any CCL5 rs2280789 G allele had longer progression-free survival (PFS) and overall survival (OS) when receiving FOLFOX+BEV than FOLFOX alone (PFS: 19.8 vs. 11.0 months, HR 0.44, 95%CI: 0.24–0.83, p = 0.004 ; OS: 41.8 vs. 24.5 months, HR: 0.50, 95%CI: 0.26–0.95, p = 0.024 )."

This literally means that there is a p=0.004 or 1/250 chance for Progression Free Survival and p=0.024 or 1/42 chance for Overall Survivability that the bevacizumab added to the chemo treatment FOLFOX (leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin) in the research above would have been produced in the FOLFOX arm alone. Only 1/250 patients in the FOLFOX only arm might have had the same Progression Free Survival (PFS) RESULTS and only 1/42 patients in the FOLFOX only arm might have had the same Overall Survivability (OS) RESULTS which were produced in the arm that combined bevacizumab (Avastin brand name which inhibits VEGF). Remember, a minimum of 1/20 chance of that happening is required for an approval.

When the CCR5/CCL5 axis is intact, VEGF is produced and if you inhibit VEGF, you suppress this cancer. If you block CCR5 with leronlimab, there is no VEGF to begin with because it cannot be made as there is so much less CCL5. Therefore, less VEGF is the same as inhibited VEGF which both lead to the control of this cancer.

The other quote From this trial who's results also bolster our current submitted protocol for Trifluridine plus Tipiracil:

"In a previous phase 3 trial, treatment with trifluridine–tipiracil (FTD–TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD–TPI in addition to bevacizumab has the potential to extend survival.

A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD–TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD–TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001)."

This literally means that there is a p=0.001 or 1/1,000 chance for PFS and p=0.001 or 1/1,000 chance for OS that the bevacizumab added to the chemotherapy FTD-TPI (trifluridine–tipiracil) in the research above would have been produced in the FTD-TPI arm alone. 1/1,000 patients in the FTD-TPI only arm might have had the same Progression Free Survival (PFS) RESULTS and 1/1,000 patients the FTD-TPI only arm might have had the same Overall Survivability (OS) RESULTS which were produced in the combination arm with bevacizumab (Avastin brand name). Remember, a minimum of 1/20 chance of that happening is required for an approval and it was achieved.

Remember, this chemotherapy + VEGF inhibitor achieved only a 6.1% ORR overall response rate. This paper shows it even less: (Patients in the bevacizumab group had a higher absolute ORR, with 5.14% (31) versus 1.37% (8)) and yet, despite this pitiful result, it has been approved. Why? Because the p-values which were achieved are better than the threshold to gain an FDA approval. It was approved to be standard of care for MSS mCRC, because 1/1,000 is 50x better than 1/20 which is the maximal p-value threshold for FDA approval.

How CytoDyn Wins in MSS mCRC is by using ORR. If you follow this post, CCR5_Whale thinks an approval in MSS mCRC would strongly benefit Samsung. Here are Some Possibilities on how the Ship Might Be Righted.

Does a victory in MSS mCRC do some serious damage to their pursuit of more expensive Band-Aids? Look, CytoDyn is on a mission. It is done losing. It has a plan and is executing on it. Regardless of the threats that are consistently posed, CytoDyn persists and their opposition eventually falls. What you see happening in the current release of this 2nd press release concerning Syneos Health, is what you shall continue to see going forward. It is a persistent, purposeful, pressing forward, within their means of course, towards the goals of fulfilling their mission.

One day or the next, the shorts are hit hard. Hard enough to make them at least stumble, crawl and hopefully, re-consider getting up or not. If these stubborn mules decide to double down, CytoDyn just keeps on, keeping on, Unstoppable in the pursuit of their mission. If you re-read that, you'll come to realize how much things have changed in just 1 year's time since that post! At some point, the shorts come upon something they won't be able to recover from or get back up from or stand up from because of their stubborn mulish attitude and refusal to back down from the hints and clues lavished upon them.

To the shorts, CytoDyn becomes a cup of trembling, a burden, which eventually wipes them out entirely, because of their obstinance and insistence on ignoring the warnings. As a dog which returns back to its own vomit, so shall the shorts be who lick up and swallow each regurgitated penny morsel. Like an asteroid out of heaven, which out of nowhere, hits the Earth, so shall it be for those who insist and persist in the shorting of CytoDyn. Out of nowhere? Yes, but only for them. Because, for years already, it has been visualized and it is widely known to be headed their way as all the research on CCR5 blockade spells out. Next, in the telescopes, it becomes brighter in the night sky, eventually though, it becomes visible with the naked eye as a star, then later still, now visible in the daytime in the blue sky and they have to hallucinate, thinking that it is headed directly for them, shaking their heads no-way, denying its presence, pretending that it is not there, they look away. It becomes a Stone on fire, out of nowhere that smites those who deny its very existence. Yes, CCR5 blockade is very real.

Why is it fair that a company going after that which is good and right be singled out, targeted and purposefully thwarted and suppressed financially, for the sole sake of killing that company? CytoDyn is not purposefully attacking anyone, yet it is constantly being barraged and attacked. Fair? Hardly. They need their expensive Band-Aids to persist as long as possible and CytoDyn wants to change that for the good of humanity. They however, are not interested in the good of humanity, but rather the good for themselves. So they attack incessantly and because of this ignorant and unrelenting short trading, disrespecting all the warning signs, they shall be hit harder than they ever have been hit before.

They shall be astonished by its blinding light, go mad and become blind. The press release above is another warning to them. CytoDyn is not pausing because of their short attacks. CytoDyn is not letting up. These short attacks only let the masses enter the stock at bargain prices. CytoDyn has capitalized because of the shorts by re-working the exercising of CYDY warrants. Many have been able to capitalize by the purchase of hundreds of thousands to millions of shares and shall become very wealthy because of the pressure the shorts have levied upon CYDY. On account of the very low share price created by these shorts, CytoDyn has been able to learn how to operate lean and mean and how to restructure and reorder priorities. It has learned to promote from within and to seek assistance when appropriate. They have become extremely creative as a result.

In this suppressed state, CytoDyn has been able to pursue (2) Phase II Clinical Trials, one in MSS mCRC and one in Inflammation and Immune Activation. They have been able to ascertain funding for the murine study in GBM and they shall be pursuing a second MASH murine study. A MASH licensing can happen any time. They have ascertained funding to go forth with an Alzheimer's Disease Pilot Study, a Chronic Fatigue Syndrome Pilot Study and (2) Pilot Studies in LATCH. In concert with OHSU and their 3rd party collaborative AI research partner, CytoDyn is unstoppable in pursuing a long acting version of leronlimab which now has been shown to also cross the placenta and may now treat many more diseases of the new born which was previously impossible because of that placenta filter. They persist in the development of an HIV-CURE.

Here Are Some Of Their Publications:

"CytoDyn has also continued to pursue publication of our existing clinical data. The (1) CD10 manuscript describing the leronlimab trial of patients with mild to moderate Covid-19 was recently accepted for publication by Clinical Therapeutics. The (2) CD02 HIV paper, the (3) CD12 manuscript on severe/critical Covid, the (4,5) twin papers on the TNBC study results, and the (6) MASH manuscript are all pending either final author review or final data confirmation prior to submission. All published research will be available on the Company’s website, soon after publication." 6 Papers Coming.

Whenever even a portion of all this begins to materialize in the coming days, weeks and months, the damage CytoDyn inflicts upon its enemies becomes increasingly more serious. You think the shorts would think twice? No way. They are not even thinking at all; they are just shorting away at the command of their puppet master. They keep their attacks up. They shall even recruit more teams in attempts to help squash this company. This is of no deterrence to CytoDyn who becomes more and more unstoppable despite these attacks. CYDY shareholders know what G does because of CytoDyn's threat to them in HIV. What might Mrk do when leronlimab threatens the treatment advance against MSS mCRC in the coming proposed clinical trial, especially when Mrk has failed in every attempt at that fight? We shall see...

Yeah, they might ramp up their attack, but like I've been saying, the asteroid is now becoming quite visible in the sky, even during the day and it has not changed its vector heading. They don't realize, but it is on a b-line straight for their heads. This is the painted picture I see.

CytoDyn needs some more time. CytoDyn has some stubborn enemies who refuse to back down in the face of a warning. Rather, instead, it motivates them to double down in denial of the plain truth right before their blind eyes. In an effort to suppress and retard, their act of aggression supports only them and in fact, actually hurts the humans they claim to support. We, the shareholders of CYDY, appreciate the asteroid as it now looms over the horizon, drawing nearer each day. Don't know when, but it shall selectively obliterate those who bet against CYDY. This has been building up for a long, long time waiting to be released. We saw it when it could not even be seen by telescope. We saw it when it had to be calculated into existence, but now it appears as an approaching star in the day, soon, it becomes like a planetary body and even then, it is ignored or discounted as if it is not even there, headed straight for them, denying its presence, its existence. Deniers of truth.

Does it rock their boat? No. There won't be anything that rocks their boat that is strong enough to make them even remotely aware of the ensuing storm they are destined to bear, destined to be slammed by, destined to be buried by. So their life boat is simply doomed to be sunk. It is doomed to be torpedoed. A couple of hits which land and cause fire on their deck doesn't communicate anything to them except that it becomes even more a reason to fight back twice as hard. Well, the MOAB is coming dear short. Think twice G and don't speak to any of your friends or family to go in with you. Heed the warning.

Hope this was helpful.