Stage Being Set

Greetings Folks. Wasn't going to post. Was hoping for some more necessary information. So far this week, we received notice that the 1st patient was dosed in the MSS mCRC Phase 2 Clinical Trial. Then, just a day later, the Abstract was released which describes the Basket Trial ColoRectal Cancer Poster which Ben Weinberg, MD shall speak for CytoDyn at ESMO in Barcelona, Spain. It is interesting that CytoDyn launches this Clinical Trial in ColoRectal Cancer at the exact same time that ESMO in GI Cancer is taking place in Barcelona, Spain.

Right off the bat, I do want to quell people's fears that an ICI would not be incorporated into CytoDyn's ColoRectal cancer trial. Look, both Dr. Lalezari and Dr. Lataillade indicated that an ICI would be incorporated.

"We have also amended our current colorectal cancer trial to ensure the prospective collection of PD-L1 data in a second type of solid tumor."

No, Clinical Trials has not yet been modified to include it, but it eventually shall be included. It would be ridiculous if they determine that PD-L1 has been upregulated and NOT recommend subsequent treatment with an ICI. If that were to happen, it would practically be medical malpractice. They are just about obligated to make that recommendation and to have the patient's own treating oncologist write a prescription for a PD-1 blockade which he/she recommends.

So, finally, the long awaited trial has begun and as per protocol, the 1st 5 shall be treated with 350mg.

"As previously mentioned, Dr. Ben Weinberg from Georgetown University and the MedStar Health Alliance will be the lead Principal Investigator for the CRC study. Per the FDA’s request, the first five patients enrolled will receive 350 mg of leronlimab SQ once/week in combination with TAS-102 and bevacizumab. After a preliminary safety review by the Data and Safety Monitoring Board (“DSMB”), subsequent patients will be randomized to 350 or 700 mg of weekly leronlimab along with the same background regimen. The DSMB will perform a second safety review after the first 20 patients have completed at least 1 cycle of therapy and can then recommend restricting further enrollment to a single dose level, if deemed appropriate."

Regardless how ridiculous this FDA request is, it is still exciting, because it has finally begun. With the added protocol of measuring CTCs and CAMLs as well as PD-L1, we can always learn something with lower doses when comparing later to the higher dosing level.

"By tracking CTC and CAML counts, and CAML size at various time points, LifeTracDx® can provide prognostic insights and predict treatment response. CytoDyn is also interested in the expressions of CCR5 and PD-L1 markers on the tumor. These markers can change over time. LifeTracDx***^(®)*** can provide this information by a blood test - no tissue is required*. The LifeTracDx**^(®)* assay will help CytoDyn to better evaluate the effectiveness of their drug."

In mTNBC, CytoDyn was able to determine how well leronlimab worked by tracking the CTC and CAML levels. When leronlimab was given, these biomarkers fell to very low levels and when they fell below a certain threshold, then the cancer was considered in remission. The rate of leronlimab administration potentially could be tapered back when in remission. But if those biomarkers were continued to be tracked, and if the levels start to increase again, then the cancer would have returned. But if leronlimab were to be resumed, it might be that the cancer would again be held in check.

This time in MSS mCRC, PD-L1 shall also be measured and when those levels exceed a certain level, then a PD-1 blockade shall be recommended by the patient's treating oncologist in order to augment the ongoing leronlimab treatment. If you remember from The Graph, MSS mCRC type cancers do not originally produce much PD-L1 at all. But following treatment with leronlimab, these MSS cancer types are prodded to produce PD-L1 on their surfaces. Then, subsequent treatment with a PD-1 blockade could very well lead to the eradication of that cancer in that individual leaving him/her with NED. No evidence of Disease. This is what had happened in the mTNBC trial and since the MSS mCRC tumors are also of the MSS type, we are expecting them to behave in the same way. This is the correlation between all the MSS tumor cancer types, 85% of all cancer types, which we are believing that leronlimab induces these tumor types to express PD-L1 on their surfaces after sufficient leronlimab treatment, thereby making them susceptible to subsequent treatment and eradication by a PD-1 inhibitor or ICI.

When only 350mg is administered, we shall learn whether or not, 350mg is sufficient to induce that subsequent upregulated PD-L1 expression or if 700mg is necessary to induce that reaction.

Now, with respect to MSS mCRC, G is not involved. Actually, CytoDyn doesn't have a direct competitor in this indication. So, G is not directly affected by CytoDyn's performance in the MSS mCRC Clinical Trial, however, they are indirectly affected. So, then, no direct engagement, but the war rages on indirectly. We are still waiting to see and hopefully the next shareholder letter shall address it, and that is, how leronlimab performed against and in combination with Trodelvy in mTNBC in the murine study. Also, along those lines, still waiting for the same concerning Keytruda. Definitely would love to hear about this in the next shareholder meeting.

Why these two? Because they are both directly involved with oncology and we have already initiated our first oncology clinical trial. Whether it is being said or not, CytoDyn is making strides in HIV as I've recently described, but this recent PR says we've dosed our 1st patient in MSS mCRC, so we are making strides in oncology. The murine studies have finished, but we need to learn what was found. Or maybe they are opting not to say anything otherwise, logical deductions may be made regarding partnerships if they were to say something about a Synergistic effect between leronlimab and Keytruda which Cyrus Arman already said.

"From a mechanistic standpoint, we believe we could get a synergistic effect with a checkpoint inhibitor,” he said.

Leronlimab is currently being trialed in combination with Keytruda (pembrolizumab) in a breast cancer xenograft model in partnership with MD Anderson Cancer Center.

Arman said CytoDyn expects to observe an enhanced anti-tumor effect from the combination and identify immunological biomarkers."

Even recently, we saw the FDA approve G's Yeztugo and that was even congratulated by CytoDyn's own Max Lataillade. In the past, G received Break Through Designation on their Trodelvy for mTNBC when leronlimab was the better choice and now, with what has been discovered regarding ICIs, a BTD should certainly be applied for and granted. It is almost imperative that CytoDyn does make this application to the FDA and I'm sure Richard Pestell, MD is on that, but, an ICI is necessary. So are they waiting for a partner, or why not just get it done by making the recommendation for an ICI once measured PD-L1 exceeds certain threshold? I think it would be alarming if this BTD is not being pursued.

So, without more information, still can't tell if this is happening or not.

Sooner or later, G is going to need to learn how to accept life living with an approval for leronlimab. It is inevitable and G needs to be able to accept it. Differences need to be worked out and it might take a bit of time, so better get started. How long does it take for there to be some kind of resolution? How long does the fighting continue?

Or is the Stage Being Set for an event that does all the decision making itself? More information is necessary. We may hear from CytoDyn next week before ESMO on Friday, 7/4/25. Doesn't seem like the company is all that concerned about share price. Maybe they feel, that issue has already been addressed and is now, no longer an issue to them. That it is pretty much done now. A non-issue.

CytoDyn is CytoDyn first. What ever it takes to get leronlimab approved and to the people. CytoDyn is still working in other indications as well, such as Alzheimer's Disease which should be starting soon. Maybe this gets a shareholder letter mention. Hopefully LATCH is mentioned, that it has begun. Prostate Cancer, Fibrosis, Stroke, GlioBlastoma Multiforme, Chronic Fatigue Syndrome are all due to be discussed. These indications are sponsored by 3rd parties and proceed forward on the 3rd party's time schedule, not CytoDyn's. But, they are done at no cost to CytoDyn.

All of this aligns with CytoDyn's main objective, in getting leronlimab approved, distributed and to the people.