Thought I'd post this on IH since Ken Chowder is a member here:
From MGK_2 on IHUB:
Pivoting Through Open Parachutes On The Payoff Of The Pre-Clinicals
This post is dedicated to Ken Chowder. You can find him frequenting Investor's Hangout. His persistence in questioning my assumption that the S-3 is predicated upon early good results in the MSS mCRC Clinical Trial led to this post. So, thank you Ken.
So many questions have arisen revolving surrounding the S-3. I've put forth the notion that the S-3 is enacted upon based on the coming trial results which I expect to be early and good. But, the completed trial is going to take over a year, and without the further influx of cash, CytoDyn's funds are expected to be running out close to the beginning of 2026 or into February. What is interesting, startling even, is that CytoDyn is not requesting any more shares to be authorized and is therefore not out-rightly wholesaling the raising of funds from retail investors.
They do have 187 million Unreserved shares remaining with which to play for use by the S-3, $100 million raise, but I don't believe that they are intending on using all those shares for the S-3. UWS has argued only between 25 and 50 million Unreserved shares to be consumed for the purposes of the S-3 to raise up to $100 million, with 137 million Unreserved shares left.
Nobody knows precisely what is going to happen absolutely. Each of us only knows vaguely based on what was said in the S-3 documentation. The S-3 is true, but we are fallible human beings. We always make mistakes, yet, because of our impatience and curiosity, we still attempt to express our opinions on how this takes place. Perhaps we have not understood something correctly. Precisely how this gets executed is anyone's guess, but we have constructed some reasonable scenarios.
Currently, upon what does CytoDyn expect its shareholder to place their hope? Aside from what they've already done and apart from the 3rd party sponsorships, what has been done as of late, which facilitates them to keep us guessing? It is the S-3. They expect us to pin our hopes upon the S-3 because of how it has been laid out, with a vast number of questions requiring answering. The fact that CytoDyn is not asking for any more shares practically screams of their utter confidence that they have a partner, otherwise, it is utter stupidity. Whether or not their confidence is predicated upon Leronlimab's expected performance regarding ORR percentage & Cold to Hot transformation, in the current MSS mCRC Clinical Trial, is questionable.
u/Upwithstock has explained that in order to raise $100 million, the Suiting company needs to pay a premium to the current share price. If CytoDyn's cash in fact runs out by February 2026, then for survival purposes, the S-3 money would need to come in by then. In fact, the S-3 money needs to come in much sooner than that simply to keep everybody sane. Oh how G would love to play on that! Ken emphasizes that the MSS mCRC Clinical Trial won't be complete by the end of 2025, in fact the completion data is estimated at 1/2028. The question becomes then, within the next few weeks to no more than mid-late September, 2025, How does the Suitor justify to their own shareholders, the Premium intended to be paid to the CYDY Unreserved share price, if the Human data of the MSS mCRC Clinical Trial is ignored completely? What then is that justification based upon?
Everybody has ideas. But the absolute authority as to how this happens is CytoDyn. CytoDyn knows that they need the money, but they are not asking for any more shares. They are not asking shareholders to dilute their shares in order to raise the money. I have brought up the fact that results should happen faster than we think and that results are open and seen as fast as they happen. But, it remains only my speculation and assumptioni that the S-3 only gets enacted upon once early favorable results are obtained and upon which they could justify paying a Premium for these Unreserved shares. The Suitor certainly knows that CytoDyn is currently cash strapped and with any good and early favorable result, could induce the Suitor to make concessions with respect of their own standards given the results are good enough. It is still very possible that the S-3 does in fact get enacted upon based on early clinical signals, and good interim results, and not necessarily full completion of the trial, but Ken has brought up preclinical/poster data which deserves a look.
Ken Chowder has suggested that the S-3 potentially gets enacted regardless of the the Clinical Trial results and instead, might possibly be due to the Pre-Clinicals which CytoDyn has recently performed, but has not yet disclosed to its shareholders. What Pre-Clinical could Ken be referring to?
Way back in the September 2024 Letter to Shareholders, Dr. Lalezari said:
"In addition to CRC, CytoDyn is investigating the role for Leronlimab in two other oncology indications via strategic and low-cost research and development opportunities, and in collaboration with several reputable institutions. I am pleased to announce that CytoDyn is working with a team of experts to resume the exploration of Triple-Negative Breast Cancer (“TNBC”), including colleagues from the University of Hawaii Cancer Center, MD Anderson Cancer Center, and the Pennsylvania Cancer and Regenerative Medicine Research Center. We will be working with this team in the coming months to design and conduct a preclinical TNBC study that will aim to confirm the mechanism of action of Leronlimab in oncology and address the question of potential synergies with both antibody-drug conjugates and immune checkpoint inhibitors. The Company intends to use this preclinical study to form the basis for a potential partnership and better inform the design of a follow-up clinical study in patients with metastatic TNBC."
In the 2/24/2025 Press Release, Dr. Lalezari said:
"Based on these survival observations, the Company has initiated two pre-clinical studies in mTNBC that will evaluate possible treatment synergies between Leronlimab, an antibody-drug complex treatment (sacituzumab govitecan), and an immune checkpoint inhibitor (pembrolizumab). The Company will also continue to perform follow-up testing on the group of mTNBC survivors who currently identify as having no evidence of ongoing disease."
In the March 2025 Letter To Shareholders, he said,
"In concert with the observation of prolonged survival in patients with mTNBC described above, CytoDyn remains focused on expeditiously resuming our clinical development in this indication. Two previously announced preclinical studies in TNBC that will identify treatment strategies to optimize the design of future studies are now underway. A third study has begun to further examine the apparent mechanism behind the observed increase in survival as compared to existing treatment paths. In the meantime, we will continue discussions with KOLs about the possibility of initiating a follow-up study in patients with mTNBC on an abbreviated timeline, based on currently available data.
The Company also continues to explore the possible use of Leronlimab in the treatment of glioblastoma multiforme (“GBM”). A preclinical study at the Albert Einstein College of Medicine sequencing temozolomide and Leronlimab is now underway. CytoDyn is also in discussions with several KOLs in neuro-oncology about the possibility of initiating a pilot study in patients with GBM, also based on currently available data."
Focusing only on mTNBC, 3 Pre-Clinical mTNBC studies were underway by March 2025; that was 6 months ago. The first question I have is if Keytruda + Leronlimab combination was already studied at MD Anderson back in 2023, why are they doing it again? Because, now they're aware of the Cold to Hot transformation whereas prior, they were not. Second question is why are they testing the combination of Trodelvy + Leronlimab? To assess for the superiority of the combination over Trodelvy alone. Third question is on the third Pre-Clinical study. "...to further examine the apparent mechanism behind the observed increase in survival as compared to existing treatment paths". If they're doing a Pre-Clinical study on the Cold to Hot transformation leading to an increase in survival, then they're doing Pre-Clinical testing on the administration of an ICI once the tumors become Hot. More than likely, they're testing Pre-Clinically, Keytruda ICI + Leronlimab combination once the Tumors have become Hot. All of these Preclinical Studies have more than likely been completed, just not discussed or further mentioned. Why not? Going all the way back to September, 2024, "The Company intends to use this preclinical study to form the basis for a potential partnership and better inform the design of a follow-up clinical study in patients with metastatic TNBC."
Going all the way back to Building Good Things, which I wrote 3 months ago on 3/25/2025, with the help of u/BuildGoodThings, I said:
"The (3) pre-clinical murine studies in mTNBC beef up a BTD application in mTNBC. An understanding of how compatible and synergistic Leronlimab is with Trodelvy and with Keytruda shall be understood and potentially included into the application for mTNBC BTD. The increased rates by which Leronlimab upregulates the expression of PD-L1 on the Tumor's cell surface shall also be obtained, disclosed and included in the same application for mTNBC BTD.
...
Enter now the cagey Big Pharmas under NDAs who are in the wings waiting... Yes, it is more than possible. We just have to wait and see. We are coming into the season now with the formation of a Phase 3 clinical trial, with the FDA acceptance of BTD in mTNBC.
The new administration is favorable to cancer's cure. BTD should not be a problem. Neither should a Phase 3 clinical trial in mTNBC. CytoDyn knows how to run the trial. Syneos Health shall likely run the Phase 3 mTNBC trial as well as they run the Phase 2 MSS mCRC trial."
In the March Letter to Shareholders, Dr. Lalezari said:
"The Company continues to be on track financially and we forecast sufficient cash and drug supply on hand to advance our clinical priorities in 2025. As we approach key milestones and announcements in the coming months, we’ll evaluate opportunities to raise additional funds at optimal times and through methods that best serve the Company and its shareholders. We believe Leronlimab has already established the potential for tremendous value in the clinic, and in the coming months we look forward to sharing the basis for that conclusion.
In sum, the developments in oncology have set the stage for 2025 to be a benchmark year for CytoDyn. This is no longer a platform drug in search of an indication; we now have compelling data to support a role for Leronlimab in solid-tumor oncology and are executing on that vision."
So, what does all this mean when it comes to the picture established by the Pre-Clinicals in mTNBC? Why hasn't CytoDyn released the results of the (3) Pre-Clinical Studies they did in mTNBC? 2/3 of these studies were performed with Keytruda ICI. Another Pre-Clinical was done in 2021-3 with Keytruda ICI at MD Anderson.
"“This investigator-initiated study is being led by Jangsoon Lee, Ph.D., assistant professor of Breast Medical Oncology Research at The University of Texas MD Anderson Cancer Center. The study is intended to determine the potential synergistic therapeutic efficacy of leronlimab in combination with immune checkpoint blockade (ICB) to attempt to raise the standard of care for breast cancer patients.”"
The most recent Pre-Clinical studies were likely led by Richard Pestell working with a team of experts to resume the exploration of Triple-Negative Breast Cancer (“TNBC”), including colleagues from the University of Hawaii Cancer Center, MD Anderson Cancer Center, and the Pennsylvania Cancer and Regenerative Medicine Research Center.
Well then, what exactly have they uncovered? They are not asking for any more shares. If the announcement of where the money is coming from, is that it is not coming resulting from the early and good data which stems from the MSS mCRC Clinical Trial, but instead, comes regardless, possibly due to the suppressed results of the Pre-Clinical murine studies in mTNBC. If so, then, would the Premium paid be justified by the results of the murine Pre-Clinicals together in conjunction with what has already been seen in the Human mTNBC Basket Trial represented by the ESMO Poster? Just maybe, the S-3 has little to do with the MSS mCRC and much more to do with the mTNBC indication.
Leronlimab was well-tolerated with few TRAEs
Significant upregulation of PD-L1 in circulating cells (i.e. CTCs or CAMLs) was identified in 76%(n=16/21) of patients after Leronlimab, and in 88 (n=15/17) of patients who received a 525mg or 700mg dose
Patients treated with Leronlimab in combination with PD-L1 ICIs had prolonged survival
N=5/5 patients who induced PD-L1 in their CTCs/CAMLs and treated with ICI concurrently or subsequently with Leronlimab were alive after 48 months, with n=4/5 currently NED (these n=5 patients had 4 median lines of any prior therapy)
Upregulation of PD-L1 after Leronlimab along with the increased overall survival observed with the combination of Leronlimab & PD-L1 ICIs warrants prospective evaluation in future mTNBC studies
In the scenario presented here, we are finding justification for the Premium S-3 paid not coming as a result of any early or good results made in the MSS mCRC Clinical Trial, but rather, would becoming on behalf of the mTNBC indication. Is the S-3 really based on the mTNBC indication and not so much the MSS mCRC Clinical Trial? Could the murine Pre-Clinical studies in mTNBC actually provide that much power if supported by the Human Basket Trial Poster Results in mTNBC? The Pre-Clinical studies in mTNBC certainly have concluded. The knowledge has been ascertained, studied and distributed to pertinent parties. Have plans been made and established based upon those Pre-Clinical results tied together with the ESMO poster? Plans would be oriented towards the development of the mTNBC indication, but certainly could help towards the MSS mCRC indication.
The question is What exactly is it that enacts the S3? The one aspect we haven't yet addressed is the one which u/sunraydoc2 has mentioned already twice or even thrice. That is the possibility that our Suitor is our nemesis G. After all, one of the Pre-Clinicals is with the antibody-drug complex treatment (sacituzumab govitecan) Trodelvy, SG. Leronlimab + SG certainly would improve greatly upon SG alone. You never know. G might have had a second calling. They might have had a change of heart. If such an offer is presented through the S-3, then, CytoDyn would be practically forced to take it, given no funds otherwise, but it must be structured as very limiting for G, but still, the problem is, that it gives them a way in. If they get a board seat, then everything, eventually would go in their direction, but it isn't.
I don't think it is with G. I think it is with Merck. I think they're looking at mTNBC primarily and want 100% of the mTNBC market. I think they're fixin to start up a transitional Phase 2/3 in mTNBC with Keytruda ICI + Leronlimab combination. That announcement could be coming leading to the enactment of the S-3, instead of an announcement of any good or early MSS mCRC Results. The S-3 might have more to do with mTNBC and less to do with MSS mCRC.
Why is this feasible? Because 28 mTNBC Human patients have already been treated in a Basket Trial where as only 6 were treated in the MSS mCRC Basket Trial. Clinically significant results were retro-actively ascertained and appreciated which quite clearly proves out that Leronlimab transforms Cold Tumors into Hot Tumors in both Trials. However, the numbers are few in both trials, but better in the mTNBC trial. Neither of these trials were designed for such purposes. But, as a result of these findings, there yet remains 5 mTNBC patients and 1 MSS mCRC who had surgery due to concomitant HCC who still remain alive 5 years following the initiation of Leronlimab + ICI. In addition, all together, (4) Pre-Clinical studies in mTNBC have been undertaken, while zero Pre-Clinical studies have been undertaken in MSS mCRC.
So maybe Ken is right and the S-3 gets executed on behalf of the mTNBC indication and then, as the MSS mCRC Clinical Trial advances along its proposed path, in a year or so, another S-3, not for $100 million, but rather, more likely for $1 billion, is drawn up, using an available 100 million shares for $10 per Unreserved share. At that point, both oncologic indications are put into play together with our Suitor and each indication would have the Human data sufficient and necessary to justify that specific level of involvement.
In this specifically addressed and proposed answer to the current quagmire at hand, the S-3 waits upon our Suitor's readiness to initiate a transitional Phase 2/3 Trial in the mTNBC indication. Therefore, just as soon as the S-3 is enacted upon, the initiation of a transitional Phase 2/3 mTNBC Clinical Trial would subsequently begin. The Protocol for such a trial would require writing. The CRO for such a trial would need to be selected. Is that what is currently being done so as to prepare for the announcement coming? Just as soon as the S-3 is enacted, overnight, CytoDyn becomes inundated with work constituting the implementation of such a hypothetical, transitional Phase 2/3 Trial in mTNBC.
CytoDyn is ready. What they have already written in their Press Releases, 10-K and S-3 is absolute. But what I write here is all conjecture circling around their absolute truths. What they've written is the authority. I am not the authority. I go by their authority though. I know a lot of this is far fetched, but in a quandary such as this, the following saying comes to mind. "A parachute doesn't work unless it is opened. And that is like a mind. A mind must be open to work."
If Ken is right, the S-3 initiates CytoDyn's restoration and it may very well begin with the mTNBC indication which would soon be followed by the MSS mCRC indication. Certainly, the Pre-Clinicals run announced over the past year of Press Releases would lead to such a conclusion.
There is a time for everything, and the time right now is for this Quandary, this Quagmire of Silence which we need to think through and that explains why I'm pivoting in so many directions right now.
From MGK_2 on IHUB:
Pivoting Through Open Parachutes On The Payoff Of The Pre-Clinicals
This post is dedicated to Ken Chowder. You can find him frequenting Investor's Hangout. His persistence in questioning my assumption that the S-3 is predicated upon early good results in the MSS mCRC Clinical Trial led to this post. So, thank you Ken.
So many questions have arisen revolving surrounding the S-3. I've put forth the notion that the S-3 is enacted upon based on the coming trial results which I expect to be early and good. But, the completed trial is going to take over a year, and without the further influx of cash, CytoDyn's funds are expected to be running out close to the beginning of 2026 or into February. What is interesting, startling even, is that CytoDyn is not requesting any more shares to be authorized and is therefore not out-rightly wholesaling the raising of funds from retail investors.
They do have 187 million Unreserved shares remaining with which to play for use by the S-3, $100 million raise, but I don't believe that they are intending on using all those shares for the S-3. UWS has argued only between 25 and 50 million Unreserved shares to be consumed for the purposes of the S-3 to raise up to $100 million, with 137 million Unreserved shares left.
Nobody knows precisely what is going to happen absolutely. Each of us only knows vaguely based on what was said in the S-3 documentation. The S-3 is true, but we are fallible human beings. We always make mistakes, yet, because of our impatience and curiosity, we still attempt to express our opinions on how this takes place. Perhaps we have not understood something correctly. Precisely how this gets executed is anyone's guess, but we have constructed some reasonable scenarios.
Currently, upon what does CytoDyn expect its shareholder to place their hope? Aside from what they've already done and apart from the 3rd party sponsorships, what has been done as of late, which facilitates them to keep us guessing? It is the S-3. They expect us to pin our hopes upon the S-3 because of how it has been laid out, with a vast number of questions requiring answering. The fact that CytoDyn is not asking for any more shares practically screams of their utter confidence that they have a partner, otherwise, it is utter stupidity. Whether or not their confidence is predicated upon Leronlimab's expected performance regarding ORR percentage & Cold to Hot transformation, in the current MSS mCRC Clinical Trial, is questionable.
u/Upwithstock has explained that in order to raise $100 million, the Suiting company needs to pay a premium to the current share price. If CytoDyn's cash in fact runs out by February 2026, then for survival purposes, the S-3 money would need to come in by then. In fact, the S-3 money needs to come in much sooner than that simply to keep everybody sane. Oh how G would love to play on that! Ken emphasizes that the MSS mCRC Clinical Trial won't be complete by the end of 2025, in fact the completion data is estimated at 1/2028. The question becomes then, within the next few weeks to no more than mid-late September, 2025, How does the Suitor justify to their own shareholders, the Premium intended to be paid to the CYDY Unreserved share price, if the Human data of the MSS mCRC Clinical Trial is ignored completely? What then is that justification based upon?
Everybody has ideas. But the absolute authority as to how this happens is CytoDyn. CytoDyn knows that they need the money, but they are not asking for any more shares. They are not asking shareholders to dilute their shares in order to raise the money. I have brought up the fact that results should happen faster than we think and that results are open and seen as fast as they happen. But, it remains only my speculation and assumptioni that the S-3 only gets enacted upon once early favorable results are obtained and upon which they could justify paying a Premium for these Unreserved shares. The Suitor certainly knows that CytoDyn is currently cash strapped and with any good and early favorable result, could induce the Suitor to make concessions with respect of their own standards given the results are good enough. It is still very possible that the S-3 does in fact get enacted upon based on early clinical signals, and good interim results, and not necessarily full completion of the trial, but Ken has brought up preclinical/poster data which deserves a look.
Ken Chowder has suggested that the S-3 potentially gets enacted regardless of the the Clinical Trial results and instead, might possibly be due to the Pre-Clinicals which CytoDyn has recently performed, but has not yet disclosed to its shareholders. What Pre-Clinical could Ken be referring to?
Way back in the September 2024 Letter to Shareholders, Dr. Lalezari said:
"In addition to CRC, CytoDyn is investigating the role for Leronlimab in two other oncology indications via strategic and low-cost research and development opportunities, and in collaboration with several reputable institutions. I am pleased to announce that CytoDyn is working with a team of experts to resume the exploration of Triple-Negative Breast Cancer (“TNBC”), including colleagues from the University of Hawaii Cancer Center, MD Anderson Cancer Center, and the Pennsylvania Cancer and Regenerative Medicine Research Center. We will be working with this team in the coming months to design and conduct a preclinical TNBC study that will aim to confirm the mechanism of action of Leronlimab in oncology and address the question of potential synergies with both antibody-drug conjugates and immune checkpoint inhibitors. The Company intends to use this preclinical study to form the basis for a potential partnership and better inform the design of a follow-up clinical study in patients with metastatic TNBC."
In the 2/24/2025 Press Release, Dr. Lalezari said:
"Based on these survival observations, the Company has initiated two pre-clinical studies in mTNBC that will evaluate possible treatment synergies between Leronlimab, an antibody-drug complex treatment (sacituzumab govitecan), and an immune checkpoint inhibitor (pembrolizumab). The Company will also continue to perform follow-up testing on the group of mTNBC survivors who currently identify as having no evidence of ongoing disease."
In the March 2025 Letter To Shareholders, he said,
"In concert with the observation of prolonged survival in patients with mTNBC described above, CytoDyn remains focused on expeditiously resuming our clinical development in this indication. Two previously announced preclinical studies in TNBC that will identify treatment strategies to optimize the design of future studies are now underway. A third study has begun to further examine the apparent mechanism behind the observed increase in survival as compared to existing treatment paths. In the meantime, we will continue discussions with KOLs about the possibility of initiating a follow-up study in patients with mTNBC on an abbreviated timeline, based on currently available data.
The Company also continues to explore the possible use of Leronlimab in the treatment of glioblastoma multiforme (“GBM”). A preclinical study at the Albert Einstein College of Medicine sequencing temozolomide and Leronlimab is now underway. CytoDyn is also in discussions with several KOLs in neuro-oncology about the possibility of initiating a pilot study in patients with GBM, also based on currently available data."
Focusing only on mTNBC, 3 Pre-Clinical mTNBC studies were underway by March 2025; that was 6 months ago. The first question I have is if Keytruda + Leronlimab combination was already studied at MD Anderson back in 2023, why are they doing it again? Because, now they're aware of the Cold to Hot transformation whereas prior, they were not. Second question is why are they testing the combination of Trodelvy + Leronlimab? To assess for the superiority of the combination over Trodelvy alone. Third question is on the third Pre-Clinical study. "...to further examine the apparent mechanism behind the observed increase in survival as compared to existing treatment paths". If they're doing a Pre-Clinical study on the Cold to Hot transformation leading to an increase in survival, then they're doing Pre-Clinical testing on the administration of an ICI once the tumors become Hot. More than likely, they're testing Pre-Clinically, Keytruda ICI + Leronlimab combination once the Tumors have become Hot. All of these Preclinical Studies have more than likely been completed, just not discussed or further mentioned. Why not? Going all the way back to September, 2024, "The Company intends to use this preclinical study to form the basis for a potential partnership and better inform the design of a follow-up clinical study in patients with metastatic TNBC."
Going all the way back to Building Good Things, which I wrote 3 months ago on 3/25/2025, with the help of u/BuildGoodThings, I said:
"The (3) pre-clinical murine studies in mTNBC beef up a BTD application in mTNBC. An understanding of how compatible and synergistic Leronlimab is with Trodelvy and with Keytruda shall be understood and potentially included into the application for mTNBC BTD. The increased rates by which Leronlimab upregulates the expression of PD-L1 on the Tumor's cell surface shall also be obtained, disclosed and included in the same application for mTNBC BTD.
...
Enter now the cagey Big Pharmas under NDAs who are in the wings waiting... Yes, it is more than possible. We just have to wait and see. We are coming into the season now with the formation of a Phase 3 clinical trial, with the FDA acceptance of BTD in mTNBC.
The new administration is favorable to cancer's cure. BTD should not be a problem. Neither should a Phase 3 clinical trial in mTNBC. CytoDyn knows how to run the trial. Syneos Health shall likely run the Phase 3 mTNBC trial as well as they run the Phase 2 MSS mCRC trial."
In the March Letter to Shareholders, Dr. Lalezari said:
"The Company continues to be on track financially and we forecast sufficient cash and drug supply on hand to advance our clinical priorities in 2025. As we approach key milestones and announcements in the coming months, we’ll evaluate opportunities to raise additional funds at optimal times and through methods that best serve the Company and its shareholders. We believe Leronlimab has already established the potential for tremendous value in the clinic, and in the coming months we look forward to sharing the basis for that conclusion.
In sum, the developments in oncology have set the stage for 2025 to be a benchmark year for CytoDyn. This is no longer a platform drug in search of an indication; we now have compelling data to support a role for Leronlimab in solid-tumor oncology and are executing on that vision."
So, what does all this mean when it comes to the picture established by the Pre-Clinicals in mTNBC? Why hasn't CytoDyn released the results of the (3) Pre-Clinical Studies they did in mTNBC? 2/3 of these studies were performed with Keytruda ICI. Another Pre-Clinical was done in 2021-3 with Keytruda ICI at MD Anderson.
"“This investigator-initiated study is being led by Jangsoon Lee, Ph.D., assistant professor of Breast Medical Oncology Research at The University of Texas MD Anderson Cancer Center. The study is intended to determine the potential synergistic therapeutic efficacy of leronlimab in combination with immune checkpoint blockade (ICB) to attempt to raise the standard of care for breast cancer patients.”"
The most recent Pre-Clinical studies were likely led by Richard Pestell working with a team of experts to resume the exploration of Triple-Negative Breast Cancer (“TNBC”), including colleagues from the University of Hawaii Cancer Center, MD Anderson Cancer Center, and the Pennsylvania Cancer and Regenerative Medicine Research Center.
Well then, what exactly have they uncovered? They are not asking for any more shares. If the announcement of where the money is coming from, is that it is not coming resulting from the early and good data which stems from the MSS mCRC Clinical Trial, but instead, comes regardless, possibly due to the suppressed results of the Pre-Clinical murine studies in mTNBC. If so, then, would the Premium paid be justified by the results of the murine Pre-Clinicals together in conjunction with what has already been seen in the Human mTNBC Basket Trial represented by the ESMO Poster? Just maybe, the S-3 has little to do with the MSS mCRC and much more to do with the mTNBC indication.
Leronlimab was well-tolerated with few TRAEs
Significant upregulation of PD-L1 in circulating cells (i.e. CTCs or CAMLs) was identified in 76%(n=16/21) of patients after Leronlimab, and in 88 (n=15/17) of patients who received a 525mg or 700mg dose
Patients treated with Leronlimab in combination with PD-L1 ICIs had prolonged survival
N=5/5 patients who induced PD-L1 in their CTCs/CAMLs and treated with ICI concurrently or subsequently with Leronlimab were alive after 48 months, with n=4/5 currently NED (these n=5 patients had 4 median lines of any prior therapy)
Upregulation of PD-L1 after Leronlimab along with the increased overall survival observed with the combination of Leronlimab & PD-L1 ICIs warrants prospective evaluation in future mTNBC studies
In the scenario presented here, we are finding justification for the Premium S-3 paid not coming as a result of any early or good results made in the MSS mCRC Clinical Trial, but rather, would becoming on behalf of the mTNBC indication. Is the S-3 really based on the mTNBC indication and not so much the MSS mCRC Clinical Trial? Could the murine Pre-Clinical studies in mTNBC actually provide that much power if supported by the Human Basket Trial Poster Results in mTNBC? The Pre-Clinical studies in mTNBC certainly have concluded. The knowledge has been ascertained, studied and distributed to pertinent parties. Have plans been made and established based upon those Pre-Clinical results tied together with the ESMO poster? Plans would be oriented towards the development of the mTNBC indication, but certainly could help towards the MSS mCRC indication.
The question is What exactly is it that enacts the S3? The one aspect we haven't yet addressed is the one which u/sunraydoc2 has mentioned already twice or even thrice. That is the possibility that our Suitor is our nemesis G. After all, one of the Pre-Clinicals is with the antibody-drug complex treatment (sacituzumab govitecan) Trodelvy, SG. Leronlimab + SG certainly would improve greatly upon SG alone. You never know. G might have had a second calling. They might have had a change of heart. If such an offer is presented through the S-3, then, CytoDyn would be practically forced to take it, given no funds otherwise, but it must be structured as very limiting for G, but still, the problem is, that it gives them a way in. If they get a board seat, then everything, eventually would go in their direction, but it isn't.
I don't think it is with G. I think it is with Merck. I think they're looking at mTNBC primarily and want 100% of the mTNBC market. I think they're fixin to start up a transitional Phase 2/3 in mTNBC with Keytruda ICI + Leronlimab combination. That announcement could be coming leading to the enactment of the S-3, instead of an announcement of any good or early MSS mCRC Results. The S-3 might have more to do with mTNBC and less to do with MSS mCRC.
Why is this feasible? Because 28 mTNBC Human patients have already been treated in a Basket Trial where as only 6 were treated in the MSS mCRC Basket Trial. Clinically significant results were retro-actively ascertained and appreciated which quite clearly proves out that Leronlimab transforms Cold Tumors into Hot Tumors in both Trials. However, the numbers are few in both trials, but better in the mTNBC trial. Neither of these trials were designed for such purposes. But, as a result of these findings, there yet remains 5 mTNBC patients and 1 MSS mCRC who had surgery due to concomitant HCC who still remain alive 5 years following the initiation of Leronlimab + ICI. In addition, all together, (4) Pre-Clinical studies in mTNBC have been undertaken, while zero Pre-Clinical studies have been undertaken in MSS mCRC.
So maybe Ken is right and the S-3 gets executed on behalf of the mTNBC indication and then, as the MSS mCRC Clinical Trial advances along its proposed path, in a year or so, another S-3, not for $100 million, but rather, more likely for $1 billion, is drawn up, using an available 100 million shares for $10 per Unreserved share. At that point, both oncologic indications are put into play together with our Suitor and each indication would have the Human data sufficient and necessary to justify that specific level of involvement.
In this specifically addressed and proposed answer to the current quagmire at hand, the S-3 waits upon our Suitor's readiness to initiate a transitional Phase 2/3 Trial in the mTNBC indication. Therefore, just as soon as the S-3 is enacted upon, the initiation of a transitional Phase 2/3 mTNBC Clinical Trial would subsequently begin. The Protocol for such a trial would require writing. The CRO for such a trial would need to be selected. Is that what is currently being done so as to prepare for the announcement coming? Just as soon as the S-3 is enacted, overnight, CytoDyn becomes inundated with work constituting the implementation of such a hypothetical, transitional Phase 2/3 Trial in mTNBC.
CytoDyn is ready. What they have already written in their Press Releases, 10-K and S-3 is absolute. But what I write here is all conjecture circling around their absolute truths. What they've written is the authority. I am not the authority. I go by their authority though. I know a lot of this is far fetched, but in a quandary such as this, the following saying comes to mind. "A parachute doesn't work unless it is opened. And that is like a mind. A mind must be open to work."
If Ken is right, the S-3 initiates CytoDyn's restoration and it may very well begin with the mTNBC indication which would soon be followed by the MSS mCRC indication. Certainly, the Pre-Clinicals run announced over the past year of Press Releases would lead to such a conclusion.
There is a time for everything, and the time right now is for this Quandary, this Quagmire of Silence which we need to think through and that explains why I'm pivoting in so many directions right now.
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