docj
7 hours ago
Posted By: Katangolo
amFAR just posted this on the website. AI? A question about an HIV cure? A question about cancer cure?
Coincidence? At the very least interesting…
https://www.amfar.org/news/can-ai-help-piece-...r-and-hiv/
Can AI Help Piece Together the Puzzle of Cancer—and HIV?
Cracking the omics code
By Andrea Gramatica, PhD
February 28, 2025
In biology, omics refers to the comprehensive study of the molecules that make up cells and organisms. This includes genomics, for example, which focuses on the entire set of genes, or proteomics, which studies all proteins. These layers of information work together to determine how cells function, interact, and respond to their environment. Understanding omics data is crucial for medical research because it provides a holistic view of biological processes and helps scientists identify disease markers, predict treatment responses, and uncover hidden mechanisms of various conditions.
Towards precision medicine
New technologies now allow scientists to study patients in much greater detail by analyzing their omics data (genes, proteins, and other biological markers). This wealth of data has been instrumental in guiding the development of tailored treatments, marking a shift towards precision medicine—therapies designed to optimize outcomes for particular groups of patients.
A major hurdle in medical research is dealing with incomplete datasets: Genetic, protein, and molecular data often come in fragments, making it difficult to draw solid conclusions. Imagine trying to complete a puzzle with missing pieces; without them, the full picture remains unclear. Scientists face a similar challenge when studying diseases.
Expert puzzle solver
A new study led by Dr. Bo Wang and colleagues at the University of Toronto, Canada, published in Nature Machine Intelligence introduces Integrate Any Omics (IntegrAO), an AI-driven tool designed to integrate fragmented biological datasets in cancer research for more precise classification. By acting like an expert puzzle solver, IntegrAO stitches together different pieces of information, ensuring no valuable data is left behind.
This technology could be a game-changer in HIV research. Over the past 40 years, numerous clinical trials and laboratory studies have been conducted on blood and tissue samples from people living with HIV at different stages of infection, in varied settings, and under diverse treatment regimens. These studies have generated enormous amounts of omics data (spanning genomics, transcriptomics, proteomics, and epigenomics), providing a deep pool of biological information. However, much of this data was collected long before AI-powered tools were available and is not structured for seamless computational analysis. As a result, the sheer volume and complexity of the data remain an untapped resource for advancing HIV therapeutics.
Patterns revealed
The type of approach described in Dr. Wang’s study presents an opportunity to change this. By integrating and harmonizing these fragmented datasets, the model could reveal patterns that were previously inaccessible, uncovering new therapeutic targets and potential pathways to a cure.
As AI-driven tools like IntegrAO continue to evolve, they offer hope for a future where science and technology work hand in hand to deliver more effective, personalized treatments for HIV, cancer, and beyond. This is the dawn of a new era in precision medicine, one where AI helps bridge the gap between big data and real-world patient care, bringing us closer to solving some of the most complex medical mysteries of our time.
Dr. Gramatica is an amfAR vice president and director of research.
docj
1 day ago
Jake2212 does't post a lot but when he does it is always worth a read:
Posted By: Jake2212
Is Gilead seriously in play to invest in LL for breast cancer? Some may recall my post shortly after last Monday's TNBC PR in which I opined that Dr Jay clearly has a good reason to invest the time and money to conduct another preclinical study for LL in mTNBC, this time with SMC Labs. I assumed then that CYDY's main focus would be on the Keytruda arm, but noted parenthetically that, because we don't know what we don't know, perhaps the Trodelvy arm might actually be the main focus.
Well, faced with the necessity to muddle through another weekend without football games to watch, I revisited the March, 2023, BioSpace article in which Cyrus had waxed eloquent about the ongoing MD Anderson mouse study involving LL and Keytruda, with his expectation of synergistic results. But no results were ever announced. Unless the study was never completed, I would think that both CYDY and MRK were furnished with the results, suggesting to me that either CYDY or MRK may have invoked a NDA to bury the results. That outcome would have been consistent with ohm's prediction that Keytruda would add nothing to LL. Therefore, no synergistic effect.
So why repeat the LL/Keytruda mouse study 2 years later? Well. unless CYDY believes that the SMC Labs mice are considerably more humanized than the MD Anderson mice, the reason escapes me.
On the other hand, Gilead's Trodelvy, the other leading FDA approved treatment for mTNBC, wasn't involved in the aforementioned MD Anderson study, but was the drug that the FDA cited to deny LL breakthrough designation status when CYDY announced LL's mTNBC phase 2 clinical trial results in August and November, 2021. Back then, LL produced a OS (overall survival) endpoint that although only slightly better than Trodelvy's, was still ongoing because more than half of the 26 women from the trial were still alive.
From last Monday's PR we now know that LL's OS was ultimately many months beyond Trodelvy's. The exact difference will undoubtedly be announced at or before the upcoming conference in Munich. Also, bear in mind that 9 of the 26 women in the trial received only 350 mg doses of LL, and only 3 received the maximum 700 mg doses. Given that the 350 mg doses would not have fully covered the CCR5 cells (thank you ohm), it may well be that the final Leronlimab OS data for the other 17 women (if over half are now deceased) will be particularly provocative compared to Trodelvy.
As I now ponder the above info, it seems much more reasonable to intuit that the LL/Trodelvy arm will be the main focus of attention for both CYDY and Gilead. According to Gilead's recently released annual report, Trodelvy produced revenue of 1.3B in 2024, all of it treating breast cancer. In Merck's annual report, I was not able to isolate Keytruda's breast cancer revenue, but I believe it would compare favorably to or exceed Trodelvy's.
MRK's sp has declined about 30% in the last 12 months, while GILD's sp has increased 70% since last June. GILD had 10B in cash at the end of 2024. And ohm has stated in a recent post that he would not be surprised if LL and Trodelvy were to produce a synergistic effect. If that proves to be true, or even if it doesn't, obtaining the use or ownership of a breast cancer drug arguably far superior to Keytruda or Trodelvy would likely translate to billions in new revenues for GILD, and that's without considering the rest of ohm's list.
Admittedly, however, MRK should also be actively engaged with CYDY concerning LL. With a faltering sp, stagnant revenues, and a Keytruda patent cliff now 2 years closer, MRK has good reason to reconsider LL in light of the newly revised Leronlimab OS that has probably already been communicated to MRK by CYDY. Because, if MRK is no longer interested in CYDY/LL, why is Keytruda still being included in the current mouse trial? And what could be better than 2 BP heavyweights being focused on the major impact that using or owning LL could have for them.
Seems very interesting to me. But bear in mind that I don't know what I don't know. And that's always problematic.
MGK_2 responded:
MGK_2
Re: Jake2212 #150709
I put together this analysis on the human mTNBC trial as depicted in this
CytoDyn Announces Preliminary Results from 30 mTNBC Patients Treated with Leronlimab. Decreases in CAMLs after 4 Doses of Leronlimab were Identified in Over 70% of Patients and were Associated with a 450% Significant Increase in Overall Survival at 12-Month Analysis
I go into an analysis of it In Preparation for the Coming Results on mTNBC
Improved Comparison of the previous PR on 7/19 and The Compassionate Use Study of LL in BC
Here is an excerpt:
Quote:
"In standard of care, the majority of TNBC patients do not make it beyond 6-7 months. In the 7/19 PR, all 21 out of the 29 patients who actually responded to the Leronlimab treatment as seen by increases in CAML and / or CTC, remained alive at the 12 month point of analysis. 21 of 29 remained alive at 12 months with a series of (4) 700mg Leronlimab injections with carboplatin, where if they were to have received Standard of Care, they would have died by the 6-7 months point. In the latest PR on Compassionate Use Study of LL in BC, the numbers, claimed are 570-980% increase in Overall Survivability, (OS); this translates into 34 to 59 months of life with scheduled, continuous weekly 350mg Leronlimab injections. That's 3 to 5 years of life with continuous weekly Leronlimab injections."
I put together this post at about that time to determine how they extrapolated to get 4 year OS
Example using Spreadsheet to Estimate Overall Survivability using available Trial Data for future prediction
Here is an excerpt:
Quote:
The Press Release gave a range from 34-59 months as Overall Survivability. The mid point of that is at 48 months or at 4 years. On my hypothetical data example of this study, we have at 48 months: the likelihood of surviving is 46.2%. But 95% confidence interval requires adding and subtracting 17.37% which gives us a Range of 28.83 - 63.57%. 50% is within this Range. So this data set could qualify to be comparable with the actual since this Range include 50% at the same 3 month time interval of 48 months.
Now, in my hypothetical data set presented here, the Overall Survivability occurs at the 3 month time interval of 42 months, since Survivability is 49.6%, (closest to 50%). Here the 95% Confidence Intervals are: 17.5% giving a range of likely survivorship from 32.1 - 67.1%. Since 67% occurs at 24 months and since 32% occurs at nearly 57 months, we have a Range of 24 - 57 months, which is somewhat similar to the results of the Press Release, (34-59) months .
Lastly, previously put together thoughts on BTD
BTD for LL on mTNBC
Here is an excerpt:
Quote:
In contrast, our Compassionate Use Study reveals an overall survivability of 34-59 months, or 3-5 years . This was determined by use of statistical analysis and extrapolating a death rate to determine time at which 50% of original 30 patients would likely be dead by, and that came out to time range.
The FDA recommended withdrawal due to the current landscape of medications for treating mTNBC. Certainly, the FDA is aware of this most recent LL study and how it utterly blows the doors off the outcome from Atezolizumab with Paclitaxel. We just may have been the reason why the FDA made this recommendation.
With regard to BTD, break through therapy designation, I believe Leronlimab is the best drug for mTNBC out there right now. No one can touch our PFS or OS. We double the stand alone Standard of Care Paclitaxel for PD-L1 BC in PFS and OS. We have no side effects stand alone , but in this Compassionate Use Study of Leronlimab in Breast Cancer, LL was combined according to each Treating Physician's Choice with any one single-agent chemotherapy drug administrated according to local practice: eribulin, gemcitabine, capecitabine, paclitaxel, nab-paclitaxel, vinorelbine, ixabepilone, or carboplatin. Side effects of chemotherapy produce considerable morbidity.
docj
2 days ago
Some nice reading on a lazy Sunday afternoon:
MGK_2
Looking Forward
Welcome Here Folks.
As for me, being honest with myself, I'm not that good at compliments. Many thanks for all your kind words. Let's remember, although it may seem so, I'm not writing for anybody's benefit, really, except for mine. I write as I see fit to document this investment and this particular modality works best for me. One of the best aspects of Reddit is that it is searchable, so that particularly helps me to find things written days, weeks, months or even years ago.
I'm just like all of you, with no inside connections, but I try to make sense of what happens throughout the week and I put it down in writing. I've stayed focused, because, like many of you, I too have a significant portion invested in CytoDyn. This is not a pulpit. I'm in the pew with all of you. As far as teaching, I don't mind. If I can, I put out some posts which educate, but I have to feel it in order to do it.
For instance, yesterday's post, Comparing And Contrasting Murine 1 mTNBC To Murine 2 mTNBC, had a bit of my own thought mixed in there. This paragraph was the brunt of that post:
"This is like a conflict posed to the company. If the combination does well on the first study, do you repeat it again on the second to confirm? If the combination does poorly on the first study, do you repeat it again to make sure? I think in such situations, common sense is used. If the finding is that the combination drug does well is so profound, or if it is only borderline good, then I say that they would decide to repeat the study to confirm the finding one way or the other. If the finding is that the combination did poorly is profound, then, they would decide not to repeat the study. If the initial finding was a borderline poor result, then the decision would be to repeat the study to validate. So with this understanding, and since they are repeating the study, I can rule out that the initial murine study was not profoundly poor using the combination of (leronlimab + Keytruda). Therefore the outcome was either borderline good or bad or profoundly good that the combination drug exceeds monotherapy. It is possible, that the anti-inflammatory effects of leronlimab do in fact improve Keytruda's capacity to destroy the mTNBC tumors."
This was all my own reasoning. We do know for sure that CytoDyn is repeating (or has already repeated) the Murine mTNBC study, but whether or not the Murine 1 mTNBC study showed statistically significant benefit of the combination (leronlimab + Keytruda) over either drug alone, can not be definitively known, at least not from that reasoning. All I was saying was that the combination, more than likely, was not unequivocally worse than Keytruda monotherapy. If that were the case, then why repeat the study? I said that if the results of Murine 1 had showed that the combination was unequivocally superior to Keytruda monotherapy, or even if the results were equivocal, then the study would likely be repeated. These were all my stipulations and I reasoned out my thinking to explain why I made certain conclusions.
It is my firm belief that the leadership at CytoDyn are rational and do think and act rationally. Seems to me that things are in fact panning out for CytoDyn, and that affirms my trust in it's leadership. Otherwise, why would I spend so much time documenting something, if I thought it was doomed to failure? Certainly, I don't believe that, but rather believe in its future success. I hope that comes through in these posts.
CytoDyn is repeating the Murine mTNBC study in combination with Keytruda and in combination with Trodelvy. Here is a ChatGPT comparison of these 2 FDA Approved mTNBC medications:
Comparison of Keytruda vs. Trodelvy in Metastatic Triple-Negative Breast Cancer (mTNBC)
Parameter Keytruda (Pembrolizumab) + Chemo Trodelvy (Sacituzumab Govitecan)
Mechanism of Action Anti-PD-1 immune checkpoint inhibitor Antibody-drug conjugate targeting Trop-2
FDA-Approved Patient Population ~25–40% of mTNBC patients (PD-L1 CPS ≥10) All mTNBC≥2 prior therapies patients after
Median Overall Survival (OS) 23.0 months (PD-L1 CPS ≥10) vs. 16.1 months (chemo alone) 11.8 months vs. 6.9 months (chemo alone)
Median Progression-Free Survival (PFS) 9.7 months vs. 5.6 months (chemo alone) 4.8 months vs. 1.7 months (chemo alone)
Treatment Line 1st-line treatment in PD-L1+ patients 2nd-line or later treatment after prior therapies
Key Benefit Significant OS benefit in PD-L1+ patients Effective in broader mTNBC population
Common Side Effects Immune-related (colitis, pneumonitis, thyroid issues) Neutropenia, diarrhea, fatigue
Key Takeaways
Keytruda is used earlier (1st-line) in PD-L1-positive (CPS ≥10) mTNBC patients (~25–40%), offering a longer OS (23 months) and PFS (9.7 months) compared to chemo.
Trodelvy is used later (2nd-line or beyond) in all mTNBC patients, providing an OS of 11.8 months and PFS of 4.8 months, but still a significant benefit for those who progress after prior treatments.
Conclusion:
If PD-L1 CPS ≥10 ? Keytruda + chemo is the preferred first-line treatment.
If PD-L1 CPS
docj
2 days ago
MGK_2
Comparing and Contrasting Murine 1 mTNBC to Murine 2 mTNBC
Just wanted to extrapolate a bit to compare and contrast the prior MD Anderson Cancer Center murine 1 study in metastatic Triple Negative Breast Cancer with the current murine 2 study in metastatic Triple Negative Breast Cancer. (mTNBC)
Here is the Time Line History:
In October 2021, This BioSpace copy of CytoDyn's Press Release CytoDyn Announces Study To Evaluate Potential Synergistic Effects Of Leronlimab With Immune Checkpoint Blockade ICB, lays out murine 1 mTNBC study. CytoDyn
"today announced a study for treating triple-negative breast cancer (TNBC) with leronlimab in a humanized TNBC xenograft model. 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.
...
We are also very grateful to Dr. Scott Kelly for arranging for this study to be conducted by Dr. Jangsoon Lee, assistant professor of Breast Medical Oncology Research at The University of Texas MD Anderson Cancer Center*.”"*
This raised the question, "Which Immune Checkpoint Blockade (ICB) was being tested in combination with leronlimab?"
The following gives an idea of how much time would be necessary for the result. 6 weeks of mouse time is equivalent to 6 years of human life. Therefore, not even a few months would be necessary to determine the approximate effectiveness of an ICB combined with Leronlimab in the treatment of mTNBC. Let's say that leronlimab has an overall survivability (OS) of about 13 months and a progression free survival (PFS) of about 6 months for mTNBC. Let's triple that for HR+ and HER2- type breast cancers where OS = 36 months and PFS = 18 months. Therefore, if 6 mice weeks = 6 human years, then 3 mice weeks = 3 human years. So therefore, the results of the effectiveness of this combination of medications should not take long at all. If the combination medication was very effective, even allowing these mice to survive for just 4 weeks, or 5 weeks after being inoculated with the cancer tumors, then we can know that the combination is very effective in MSS tumor types. MSS being Microsatellite stable, which are a type of tumor which are very difficult to treat, but 85% of breast cancer is MSS. Keytruda alone is only indicated currently to treat MSI or Microsatellite Instability. But, Keytruda + leronlimab could become indicated to treat the MSS tumor population or about 2,000% more than what it currently treats in breast cancer alone. If it is found that leronlimab allows some of its mTNBC patients to remain alive for 4 years after treatment, they would be considered Cured. mTNBC patients usually don't live beyond 1 year following diagnosis. HR2+ and HER2- patients could live 3 years post diagnosis, but not mTNBC patients.
Now, the results of this study were never publicly released because the data was owned by MD Anderson. Scott Kelly originally set the trial up with MD Anderson in partnership with CytoDyn. The data was only disclosed to CytoDyn, but the hard data & Results were not given to CytoDyn. They were only shown the results. If they wanted the hard results to work with the data, they would need to purchase it from MD Anderson and that was not done because of costs. But they saw what they needed to see.
They wanted to determine whether there was any benefit to combining leronlimab with a check point inhibitor, PD-1 blockade, and they had a look at the data and got an answer, but never said one way or the other what they found.
Continuing on with the time line, 18 months after murine 1 mTNBC started, in March of 2023, in the BioSpace Article Embattled CytoDyn Sets New Course Towards NASH, Tough Tumors, Cyrus Arman related,
"Along with NASH, CytoDyn will focus primarily on oncology*. Here, the company* will target colorectal cancer and hormone receptor-positive, HER2-negative breast cancer.
These are both areas where checkpoint inhibitors have failed to show efficacy when added to a standard-of-care backbone, Arman said, adding that leronlimab has shown positive signals in both.
“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.
In terms of future partnerships, Arman isn’t concerned that CytoDyn’s history will have a negative effect.
“I think that most companies are data-first,” he said. “If we come and we show the data that we have…I think they’ll see, here’s an organization that has transformed from what it used to be.”"
Cyrus let us know, that the Immune Checkpoint Inhibitor was with Merck's Keytruda, pembrolizumab. "Arman said CytoDyn expects to observe an enhanced anti-tumor effect from the combination and identify immunological biomarkers." But Cyrus said this 18 months after the study began. Does that make any sense? By that time, the study had already concluded. CytoDyn had already been shown the results. CytoDyn already knew whether or not there was an improvement over leronlimab monotherapy by combining leronlimab with Keytruda against mTNBC. Nevertheless, Cyrus made the statement and he was comfortable making this statement in the BioSpace Article 18 months after the study began. CytoDyn was comfortable because the outcome of the study was likely favorable towards the combo treatment over leronlimab monotherapy."
Yet another 18 months of mTNBC hiatus passes, and then in the September 2024 Letter To Shareholders, mTNBC is reintroduced:
"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."*
Then, close to Thanksgiving time of 2024, CytoCyn Appoints Richard Pestell MD, PHD As Lead Consultant In Oncology.
"He is currently the President of the Pennsylvania Cancer and Regenerative Medicine Research Center*, a part of the Baruch S. Blumberg Institute in Doylestown, Pennsylvania. Prior to this role, he spent a decade at Thomas Jefferson University in Philadelphia, Pennsylvania, serving as Director of the Sidney Kimmel Cancer Center, Chairman of the Department of Cancer Biology and Executive Vice President. Dr. Pestell’s work has been published in over 600 publications, and his research has been credited with well over 95,000 citations. He previously served as Vice Chairman of the Board, and* Chief Medical Officer (CMO), spearheading the Company’s successful effort to obtain Fast Track Designation from the FDA for the use of leronlimab in combination with carboplatin for the treatment of patients with CCR5-positive metastatic triple-negative breast cancer. In addition, Dr. Pestell was instrumental in designing and initiating CytoDyn’s Phase 1b/2 clinical trial in that indication*."*
Lastly on the Timeline, most recently, on February 24, 2025, CytoDyn released CytoDyn Announces Promising Survival Observations In mTNBC Patients Treated With Leronlimab. This Press Release discusses the Phase 1b/2 clinical trial that Dr. Pestell initiated referenced just above. The resulted data of that clinical trial were delayed due to the actions of CytoDyn's CRO at the time, Amarex. Over the past few years, CytoDyn worked to obtain this data and has the results.
"...today announced encouraging survival outcomes among a group of patients with metastatic triple-negative breast cancer (“mTNBC”) treated with leronlimab.
... In addition, the Company confirmed that a small group of patients who failed treatment after developing metastatic disease survived more than 36 months after receiving leronlimab, are alive today, and currently identify as having no evidence of ongoing disease*.*
... Following the resolution of the Company’s dispute with its former CRO, CytoDyn obtained follow-up records from patients treated with leronlimab during the Company’s prior clinical trials in oncology. After confirming these patient outcomes*, CytoDyn worked with consultants and key opinion leaders to summarize the findings and submit an abstract to the* European Society for Medical Oncology (ESMO) Breast Cancer meeting taking place in Munich, Germany, from May 14 to 17, 2025*.*
“We are encouraged by the longer-term survival data to pursue this potentially paradigm-shifting therapeutic pathway for patients suffering from metastatic triple-negative breast cancer,” said Richard Pestell, MD, PhD, AO, the Company’s Lead Consultant in Preclinical and Clinical Oncology. “As a cancer therapeutic, leronlimab was well tolerated with remarkably infrequent treatment-related adverse events. These promising results suggest further studies with leronlimab are warranted to expand oncology treatment options and improve patient care.”
Dr. Jacob Lalezari, CEO of CytoDyn, added: “These provocative observations of improved survival in patients with mTNBC and prior treatment failure in the metastatic setting, including reported clearance of disease in a group of long-term survivors, provides early clinical evidence of leronlimab’s potential impact in the treatment of TNBC and other solid tumors*. I expect the Company’s oncology efforts to accelerate in the coming months, with* further announcements in both mTNBC and colorectal cancer*.”*
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."
So, this last paragraph is where we are at right now. End of the History Time Line. Discussion.
Everything written in this most recent February 2025 Press Release was also known in the September 2024, Letter To Shareholders. They are way ahead of what they announce. In September, 2024, CytoDyn knew they would be doing murine studies again in mTNBC.
"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.*"
They knew back in September, 2024, that they would be combining leronlimab with both Gilead's Trodolvy (sacituzumab govitecan) and Merck's Keytruda (pembrolizumab). February 2025 PR was just a delayed release of knowledge which they already had back in September of 2024. They needed the time in between for Pestell to come on board, and his team of experts to get organized to take a look at the prior MD Anderson murine 1 study which was set up by Scott Kelly, and extract out of it, the pertinent information which would be useful and design and initiate an appropriate combination murine 2 study in mTNBC that would use leronlimab in combination with both Keytruda and Trodelvy.
My main question is, "Why did they choose to include another combination of leronlimab + Keytruda?" Remember, Cyrus Arman hinted that the results were good?
“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."
This is like a conflict posed to the company. If the combination does well on the first study, do you repeat it again on the second to confirm? If the combination does poorly on the first study, do you repeat it again to make sure? I think in such situations, common sense is used. If the finding is that the combination drug does well is so profound, or if it is only borderline good, then I say that they would decide to repeat the study to confirm the finding one way or the other. If the finding is that the combination did poorly is profound, then, they would decide not to repeat the study. If the initial finding was a borderline poor result, then the decision would be to repeat the study to validate. So with this understanding, and since they are repeating the study, I can rule out that the initial murine study was not profoundly poor using the combination of (leronlimab + Keytruda). Therefore the outcome was either borderline good or bad or profoundly good that the combination drug exceeds monotherapy. It is possible, that the anti-inflammatory effects of leronlimab do in fact improve Keytruda's capacity to destroy the mTNBC tumors.
Considering the above paragraph, it is my suspicion that CytoDyn has chosen to repeat the combination of (leronlimab + Keytruda) in the new murine 2 studies with Richard Pestell against mTNBC because the initial MD Anderson murine 1 study probably did show that the combination of these two drugs was better than leronlimab alone against both MSS mTNBC. I tend to believe that if the original MD Anderson murine 1 study did not show any improvement what-so-ever of the combination of (leronlimab + Keytruda) over leronlimab monotherapy, then they would not have decided to confirm their findings by including Keytruda, in this second up coming study. There was enough good in the initial murine 1 study to warrant a repeat and confirmation of those good findings. Why validate a profoundly poor result by making the same mistake twice? Rather, the decision to validate the good is profoundly better.
If this conjecture proves to be the outcome of the 2nd murine mTNBC study, then this combination of (leronlimab + Keytruda) would give Merck the indication to treat 100% of MSS mTNBCs. Merck already has Keytruda's right to treat MSI mTNBC tumors. Right now, Keytruda alone may treat MSI type tumors, but not MSS type tumors. That is only 15% of all mTNBC tumors. But, if this combination is proven to be more effective than leronlimab alone, then 100% of mTNBC tumors become treatable by the combination drug. Chances of Merck offer just went up greatly.
As for Gilead's Trodelvy, sacituzumab govitecan, the combination of this antibody-drug conjugate with leronlimab, would be the 1st time this combination is being studied, but could very well be better than leronlimab alone by simply considering the fact that each drug has its own distinct mechanism of action and the combination could prove to exceed the monotherapy of either. Leronlimab's anti-inflammatory effects could bolster Trodelvy's capacity to fight the disease and make its contribution much greater that without leronlimab. If this becomes the outcome of this combination study, the possibility of getting an offer from Gilead greatly increases. Because, then, CytoDyn would have virtually (2) Cures in Indications Gilead already is in, HIV and mTNBC.
When we get to European Society for Medical Oncology (ESMO) Breast Cancer meeting taking place in Munich, Germany, from May 14 to 17, 2025*.* , these patients will already have been Breast Cancer Free for 48 months, in other words 4 years without BC = Cured. 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.
The implications that what Richard Pestell & CytoDyn are doing in conducting this confirmatory combination murine 2 study in mTNBC are huge. You don't repeat a study when initially, it's a total failure. We already know it is not a failure from the human trial, because as stated in the latest Press Release, some patients are still alive nearly 4 years after taking leronlimab, when most would have already died at most 1 year after contracting the disease. Remember, don't confuse mTNBC and HR+ or HER2- cancers. CytoDyn is expanding on what they already know from prior human trials and prior murine studies. More specific knowledge shall be gained, such that the next human clinical trial in mTNBC leads to leronlimab's approval. What a journey Folks!
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