Pristine_Hunter_9506

CytoDyn’s Integrated Biomarker Strategy: Tracking the Impact of Leronlimab
Abstract CytoDyn has dedicated significant resources to the identification, tracking, and interpretation of biomarkers in its clinical and preclinical programs. Central to these efforts is the development of leronlimab—a CCR5-blocking monoclonal antibody—and its impact on processes such as RANTES-mediated inflammation, tumor metastasis, and fibrosis. This article reviews the company’s work in monitoring biomarkers to optimize patient selection, evaluate treatment responses, and support regulatory submissions.

Introduction Biomarkers play an essential role in modern drug development by linking a therapeutic agent’s mechanism of action to clinical outcomes. In the case of leronlimab, tracking key biomarkers such as RANTES levels, CCR5 expression, and other inflammatory mediators has become a cornerstone of CytoDyn’s development strategy. Through a series of rigorous preclinical studies and clinical trials, CytoDyn aims to demonstrate that modulation of these biomarkers corresponds with meaningful therapeutic benefits in areas ranging from oncology and HIV to fibrotic liver diseases.

Clinical Applications and Biomarker Tracking Oncology Studies CytoDyn has integrated biomarker tracking into its clinical evaluations of leronlimab in oncology. Notably:

Investigator-Initiated Studies in Triple-Negative Breast Cancer (TNBC): In a humanized TNBC xenograft model led by researchers at MD Anderson Cancer Center, CytoDyn’s study has utilized immunohistochemistry (IHC) to assess CCR5 expression as a key biomarker. This work aims to correlate changes in the tumor microenvironment, including the modulation of RANTES and other cytokines, with anti-tumor activity. The study’s goals include identifying immunological biomarkers that not only validate leronlimab’s mechanism of action but might also prove useful for patient stratification in future trials .

Phase II Studies in Colorectal Cancer: In recent work, CytoDyn completed an FDA meeting regarding its Phase II study in microsatellite stable metastatic colorectal cancer (mCRC). This trial employs IHC and next-generation sequencing (NGS) to detect CCR5 expression on tumor cells. By doing so, the company seeks to determine whether elevated CCR5 in tumors can predict a more robust response to leronlimab when used in combination with standard agents, such as TAS-102 and bevacizumab .

Fibrosis and Inflammatory Pathways Preclinical Models of Liver Fibrosis: In collaboration with SMC Laboratories, CytoDyn has published findings from preclinical studies that demonstrated statistically significant fibrosis reversal in animal models of metabolic dysfunction-associated steatohepatitis (MASH) and chemically induced liver fibrosis. In these models, biomarker tracking—through both histological examinations and molecular assays—was fundamental to showing that leronlimab’s binding to CCR5 may downregulate pathways leading to liver fibrosis. These results are promising for future clinical applications in fibrotic diseases of the liver and potentially other organs .

Infectious Diseases and Immune Modulation COVID-19 and Inflammatory Biomarkers: Beyond oncology and fibrosis, early compassionate use studies during the COVID-19 pandemic suggested that leronlimab could reduce inflammatory mediators such as RANTES. This effort involved serial biomarker assessments to monitor the drug’s effect on cytokine levels, thereby lending support to its potential role in modulating the immune response during severe viral infections.

Strategic Advantages of Biomarker Integration The depth of CytoDyn’s biomarker research confers several strategic advantages:

Enhanced Patient Selection: By identifying patients with high CCR5 expression or elevated inflammatory markers, CytoDyn’s trials can enroll the most responsive patient populations. This targeted approach can improve the signal-to-noise ratio in clinical endpoints.

Adaptive Trial Designs: Biomarker data support the incorporation of adaptive designs, where interim analyses of biomarker trends (such as reductions in RANTES) inform adjustments in dosing, patient stratification, or even modifications of trial endpoints. Such flexibility can accelerate the clinical development timeline.

Regulatory Engagement: Consistent and reproducible biomarker data strengthen the argument for a drug’s mechanism of action. Regulators increasingly see value in surrogate endpoints, particularly when they reliably predict clinical outcomes. CytoDyn’s extensive biomarker tracking is being positioned as a linchpin to its regulatory strategy.

Conclusion CytoDyn’s commitment to tracking biomarkers has been a driving force in the development of leronlimab. From using immunohistochemistry to evaluate CCR5 expression in tumor tissues to monitoring cytokine profiles in clinical trials, the company’s integrated biomarker strategy is central to demonstrating the drug’s impact on key pathological processes. This rigorous biomarker-driven approach not only aids in optimizing patient selection and dosing but also lays a solid foundation for future regulatory approval and clinical success across multiple therapeutic areas.

By continually refining their assays and integrating adaptive trial designs, CytoDyn is well positioned to leverage biomarker data as a surrogate for clinical efficacy, thereby accelerating the path for leronlimab’s broader acceptance as a transformative therapeutic option.

Would you like to dive deeper into specific assay methodologies or examine further case studies on how biomarker tracking has influenced other drug approvals?

Advances in Assay Methodologies for Biomarker Tracking

Immunohistochemistry (IHC) Application: IHC remains one of the most widely used techniques for visualizing protein expression in tissue sections. For CytoDyn, IHC can be used to assess CCR5 expression on tumor cells or infiltrating inflammatory cells in biopsy samples. When evaluating leronlimab’s efficacy, researchers can compare the intensity and distribution of CCR5 or associated markers (like RANTES) before and after treatment.

Advantages: IHC provides spatial context, allowing researchers to understand not only if the target is present, but also its localization within the tumor microenvironment or inflammatory sites. This approach is particularly important in oncology, where the expression profile can vary widely within a tumor.

2. Enzyme-Linked Immunosorbent Assays (ELISA) Application: ELISAs are well-suited for quantitative measurement of soluble biomarkers in blood or other bodily fluids. In the context of leronlimab, ELISA can be used to track changes in serum RANTES levels over time. Frequent sampling during clinical trials helps determine the pharmacodynamic impact of CCR5 blockade.

Advantages: ELISA is highly sensitive, specific, and can be standardized easily, making it an excellent method for routine monitoring in both preclinical and clinical settings. Its quantitative nature facilitates correlation with clinical endpoints.

3. Multiplex Assays Application: Multiplex platforms, including bead-based assays, allow for the simultaneous measurement of multiple cytokines and chemokines (e.g., RANTES, other inflammatory markers) in a single sample. This approach helps capture a holistic view of the inflammatory pathway modulation.

Advantages: By tracking several biomarkers at once, researchers can identify patterns of response and better understand the broader immunomodulatory effects of leronlimab. Multiplexing enhances efficiency and provides deep insights into pathway networks.

4. Next-Generation Sequencing (NGS) and RT-PCR Application: NGS and quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) can be used to assess gene expression levels of CCR5, RANTES, and related inflammatory genes. Such studies are vital for confirming that observed protein-level changes are reflected in mRNA levels.

Advantages: These methods offer high sensitivity and specificity, enabling the detection of subtle shifts in gene expression in response to treatment. They are especially useful in developing companion diagnostics to predict which patients might benefit most from therapy.

Case Studies: Biomarker Tracking Influencing Drug Approvals

Trastuzumab (Herceptin) for HER2-Positive Breast Cancer Companion Diagnostic: One of the hallmark examples of successful biomarker-driven therapy is the use of trastuzumab in HER2-positive breast cancer patients. The approval of trastuzumab was tightly linked to IHC and Fluorescence In Situ Hybridization (FISH) assays that reliably determined HER2 overexpression or gene amplification.

Impact: Integration of these diagnostic tests ensured that only patients with a demonstrated overexpression of HER2 received the treatment, significantly increasing the drug’s efficacy and safety profile in the targeted population.

2. Pembrolizumab (Keytruda) for PD-L1-Positive Tumors Companion Diagnostic: Pembrolizumab’s approval in several cancers was accompanied by the development of a companion diagnostic assay that measures PD-L1 expression. This biomarker was crucial for selecting patients most likely to respond to immunotherapy.

Impact: The ability to stratify patients based on PD-L1 expression strengthened the clinical trial results, reduced heterogeneity in patient responses, and led to a more accelerated regulatory review process.

3. CAR T-Cell Therapies in Hematologic Malignancies Biomarker Integration: In the development of CAR T-cell therapies for certain leukemias and lymphomas, biomarkers, such as specific cell surface antigens (e.g., CD19), are used both for patient selection and for monitoring therapeutic effectiveness post-infusion.

Impact: Tracking these biomarkers has contributed to understanding the durability of responses and has driven further refinements in therapy design, ultimately paving the way for regulatory approvals.

Conclusion and Future Directions CytoDyn’s approach to tracking biomarkers leverages a multi-method strategy—ranging from IHC and ELISA to multiplex assays and NGS—to comprehensively monitor the impact of leronlimab on pathways driven by CCR5 and RANTES. The success stories from drug approvals that depend on companion diagnostics, such as trastuzumab and pembrolizumab, serve as guiding examples. These case studies illustrate how robust biomarker tracking not only enhances patient selection and assesses therapeutic efficacy but also significantly impacts the regulatory landscape by providing tangible surrogate endpoints.

Going forward, a combined strategy that incorporates adaptive trial designs with rigorous biomarker monitoring could position leronlimab favorably for achieving broader approval. Continuous refinement in assay methodologies and further integration of real-world evidence will also be key in demonstrating sustained clinical benefits and solidifying the drug’s place in precision medicine.

https://content.govdelivery.com/accounts/USFDA/bulletins/3db648d


US Food and Drug Administration
FDA Announces Plan to Phase Out Animal Testing Requirement for Monoclonal Antibodies and Other Drugs
Today, the U.S. Food and Drug Administration is taking a groundbreaking step to advance public health by replacing animal testing in the development of monoclonal antibody therapies and other drugs with more effective, human-relevant methods. The new approach is designed to improve drug safety and accelerate the evaluation process, while reducing animal experimentation, lowering research and development (R&D) costs, and ultimately, drug prices.

The FDA’s animal testing requirement will be reduced, refined, or potentially replaced using a range of approaches, including AI-based computational models of toxicity and cell lines and organoid toxicity testing in a laboratory setting (so-called New Approach Methodologies or NAMs data). Implementation of the regimen will begin immediately for investigational new drug (IND) applications, where inclusion of NAMs data is encouraged, and is outlined in a roadmap also being released today. To make determinations of efficacy, the agency will also begin use pre-existing, real-world safety data from other countries, with comparable regulatory standards, where the drug has already been studied in humans.

“For too long, drug manufacturers have performed additional animal testing of drugs that have data in broad human use internationally. This initiative marks a paradigm shift in drug evaluation and holds promise to accelerate cures and meaningful treatments for Americans while reducing animal use,” said FDA Commissioner Martin A. Makary, M.D., M.P.H. “By leveraging AI-based computational modeling, human organ model-based lab testing, and real-world human data, we can get safer treatments to patients faster and more reliably, while also reducing R&D costs and drug prices. It is a win-win for public health and ethics.”

Key Benefits of Replacing Animal Testing in Monoclonal Antibody Safety Evaluation:

Advanced Computer Simulations: The roadmap encourages developers to leverage computer modeling and artificial intelligence to predict a drug’s behavior. For example, software models could simulate how a monoclonal antibody distributes through the human body and reliably predict side effects based on this distribution as well as the drug’s molecular composition. We believe this will drastically reduce the need for animal trials.

Human-Based Lab Models: The FDA will promote the use of lab-grown human “organoids” and organ-on-a-chip systems that mimic human organs – such as liver, heart, and immune organs – to test drug safety. These experiments can reveal toxic effects that could easily go undetected in animals, providing a more direct window into human responses.

Regulatory Incentives: The agency will work to update its guidelines to allow consideration of data from these new methods. Companies that submit strong safety data from non-animal tests may receive streamlined review, as the need for certain animal studies is eliminated, which would incentivize investment in modernized testing platforms.

Faster Drug Development: The use of these modern techniques should help speed up the drug development process, enabling monoclonal antibody therapies to reach patients more quickly without compromising safety.

Global Leadership in Regulatory Science: With this move, the FDA reaffirms its role as a global leader in modern regulatory science, setting new standards for the industry and encouraging the adoption of innovative, humane testing methods. In recent years, Congress and the scientific community have pressed for more human-relevant testing methods. Today’s announcement is a step by the FDA towards its commitment to modernize regulatory science as technology advances.
Working in close partnership with federal agencies such as the National Institutes of Health, the National Toxicology Program and the Department of Veterans Affairs, the FDA aims to accelerate the validation and adoption of these innovative methods through the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). The FDA and federal partners will host a public workshop later this year to discuss the roadmap and gather stakeholder input on its implementation. Over the coming year, the FDA aims to launch a pilot program allowing select monoclonal antibody developers to use a primarily non-animal-based testing strategy, under close FDA consultation. Findings from an accompanying pilot study will inform broader policy changes and guidance updates expected to roll out in phases.

Commissioner Makary noted the far-reaching significance of this proposal. “For patients, it means a more efficient pipeline for novel treatments. It also means an added margin of safety, since human-based test systems may better predict real-world outcomes. For animal welfare, it represents a major step toward ending the use of laboratory animals in drug testing. Thousands of animals, including dogs and primates, could eventually be spared each year as these new methods take root.”

Posted By: mightycydy
Leronlimab for stroke recovery?

"Preclinical systematic review of CCR5 antagonists as cerebroprotective and stroke recovery enhancing agents"

Link:
https://elifesciences.org/articles/103245

Highlights:
The overall body of preclinical evidence for CCR5 antagonists in stroke demonstrates potential acute cerebroprotection with corresponding impairment reduction, as well as improved functional recovery in the subacute/early chronic phase.

In conclusion, CCR5 antagonists show promise in preclinical studies for stroke cerebroprotection, corresponding reduction in impairment, as well as improved functional recovery related to neural repair in the late subacute/early chronic phase.

_________________________

On a related note, from the March 2025 Cytodyn Letter to Shareholders:
A new collaborator, Dr. Tom Carmichael, Professor and Chair of Neurology at the University of California, Los Angeles, has published important preclinical observations demonstrating how a small molecule CCR5 inhibitor can expedite recovery following a cerebrovascular accident (“CVA” or “stroke”). CytoDyn is working with Dr. Carmichael and Dr. Kate Schunke at the University of Hawaii to conduct a preclinical study of stroke in transgenic mice that express human CCR5. We are excited by this initiative, given our view that there is an unmet need for innovative and effective treatment paths for patients in this category, and our belief that the market for therapies to treat stroke and/or traumatic brain injury could grow significantly over the next several decades. Dr. Carmichael will also be advising on the pilot study of AD to be initiated at Cornell Medical Center in New York.

Four prominent scientists, included one American, Dr. Richard Pestell, have received funding by the Research Hungary (HUN-REN) program for high impact research (read more here).

The HUN-REN program’s five-year $2.6 million grant will support Dr. Pestell’s groundbreaking studies to overcome therapy resistance of breast cancer.

A Distinguished Professor at the Blumberg Institute, Dr. Pestell says the EU award provides an ideal collaboration with Blumberg Institute colleagues in medicinal chemistry.

Known best for his discoveries on cell-cycle and cyclins, Dr. Pestell’s IND-enabling studies led to the development of cyclin dependent kinase inhibitors, that are now used widely for types of breast cancer. He is currently ranked #1 by Google scholar for his field of cell-cycle .

For his landmark research discoveries over the last 30 years Dr. Pestell , has received numerous awards including Election as a foreign member of Academia Europaea (AE), and received the order of Australia from Queen Elizabeth II.

Dr. Pestell is a medical oncologist who previously led two NCI cancer centers, served as the Executive Vice President of Thomas Jefferson University and founded 5 biotechnology companies in cancer treatment and diagnostics.

Read more about Dr. Pestell here.

https://blumberginstitute.org/faculty-news-blumberg-institute-scientist-receives-2-6-million-grant-from-the-research-grant-hungary-program/

MGK_2

In A League Of Its Own
Is leronlimab like any other drug? The drug has one simple task. To block CCR5 and it does that flawlessly at 100% Receptor Occupancy every time. It holds that RO for quite some time, a good, long 2-3 week half life in its current form. So, doing its job really is not an issue at all. That is because blocking CCR5 is not the challenge at hand.

For leronlimab to "work" as expected, it relies squarely upon the immune system to do its own job. If some thing is askew, if something is amiss within that complex immunomodulatory cascade, then the entire mechanism would misfire, because the next step would rely upon the current step which had relied upon the prior step. Everything must remain operating as it was originally designed to work so that the outcome obtained would be what the Designer had intended.

"YOU LIVE OR DIE BY THE IMMUNE SYSTEM

TC 01:05:22: So I wanna actually, can I stop and ask you a question, though? So your position is that cancer, but not just cancer, all kinds of illnesses are caused by weakened immune system and inflammation.



PSS 01:05:35: It's all about the immune system. Your body functions. You live or you die by the immune system. The senescent cells, aging is the immune system. The cells in your body that allow you to go to a hundred years old, a hundred and 20 years old, is based on the activity and the function of the immune system because the immune system is what's regulating your healthy cells."

The drug is not doing the work after all; rather, it is the immune system which accomplishes the healing because the drug only provides for the cellular milieu within the immune system and that is conducive to allowing the immune system to unimpededly perform its intended function.

The drugs which leronlimab is up against, or which might be combined with, so as to augment, are all owned and operated by Big Pharma. Those drugs are worth billions of dollars and they have made even more billions for their owners. King Keytruda. The Crowned Head Humira. Overlord Ozempic. "My" Majesty Mounjaro. Kaiser Skyrizi and on and on...

Some of these which I mention are out; some are on their way out while others are just getting started. It is through these that Big Pharma lifts up their voice. This establishes them as the partial prince of the power of puerility.

What do these blockbusters all have in common? They all target some small molecule within the body. Keytruda (pembrolizumab) targets the programmed cell death protein 1 (PD-1) receptor, which is found on the surface of activated T cells. By binding to PD-1, Keytruda blocks its interaction with the ligands PD-L1 and PD-L2, which are often expressed by certain cancer cells to suppress immune responses. This inhibition restores the immune system's ability to recognize and attack tumor cells.

Humira (adalimumab) targets tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in inflammatory and immune responses. By binding to TNF-alpha, Humira blocks its interaction with TNF receptors on cell surfaces, thereby reducing inflammation and the immune system's attack on healthy tissues. This mechanism is particularly effective in treating autoimmune diseases such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, and others

Ozempic (semaglutide) targets the glucagon-like peptide-1 (GLP-1) receptor. It acts as a GLP-1 receptor agonist, mimicking the effects of the naturally occurring hormone GLP-1. This activation leads to several beneficial effects:

Blood glucose regulation: Enhances glucose-dependent insulin secretion, reduces glucagon release, and slows gastric emptying, which helps control blood sugar levels.

Weight loss: Reduces appetite, food cravings, and energy intake by acting on GLP-1 receptors in the brain and gastrointestinal tract, contributing to decreased body weight.

These mechanisms make Ozempic effective for managing type 2 diabetes and obesity.

Mounjaro (tirzepatide) targets two key receptors: GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). This dual mechanism enhances insulin secretion, reduces glucagon levels, slows gastric emptying, and decreases food intake. These actions improve blood sugar control and promote weight loss in adults with type 2 diabetes and obesity.

Skyrizi (risankizumab) targets the interleukin-23 (IL-23) cytokine, specifically its p19 subunit. By binding to this subunit, Skyrizi prevents IL-23 from interacting with its receptor, thereby inhibiting downstream inflammatory signaling pathways. This mechanism reduces inflammation and is effective in treating conditions such as plaque psoriasis, psoriatic arthritis, and Crohn's disease.

For each case, a different molecule is targeted. One drug/molecule has nothing to do with the other drug/molecule. In most cases, the targeting of a certain molecule results in a known or predictable outcome. In every case, that outcome has been shown to be statistically significant in leading towards a measurable improvement of certain specific symptoms in a particular disease. In some instances, it results in the improvement of symptoms in only one or two diseases, while in other instances, multiple diseases are impacted. Keytruda has been found to be helpful in an array of cancers, and likewise, Humira has been proven helpful in rheumatoid arthritis, Crohn's disease, ulcerative colitis and psoriasis. Ozempic and Mounjaro are shown helpful in Diabetes and Weight loss, while Skyrizi in psoriasis and Chron's disease.

Turning back to leronlimab, what is its target? CCR5. But CCR5 is not a small receptor. Yes, size-wise, it is tiny. Quantity wise, it is extremely numerous. As for its location, CCR5 acts as Chief Lieutenant General of the entire militia. GPS of the Army, Navy, Air Force and Marines of our immune system. This special Receptor CCR5, governs the action of our Defenses and Offenses which operate against every disease and pathologic antigen invader.

"JL 16:24: What CCR5 does in the body, it's kind of like the GPS system of the Immune System. So it controls the movement of cells. It tells cells where they want to go and how they want to arrive. So, for example, we said in the cancer model that we were working, in the cancer, cells secrete this thing called RANTES which attracts these CCR5 positive cells which then surround the tumor and protect it from other cells of the Immune System that would try and get in and kill it and then by triggering CCR5 on Tissue Macrophages, those Macrophages, their polarization is altered, so that instead of attacking the cancer cells, they're now helping to build blood vessels, to help the cancer grow."

First off, by blocking CCR5, leronlimab prevents HIV and if performed with some degree of creativity, HIV is currently on the verge of a cure via leronlimab's CCR5 blockade. Leronlimab's capacity to block CCR5, in only the way which it can do, does so much more than just completely block HIV's progression. It also helps to prevent and eradicate all sorts of tumor types along with their associated cancerous metastases, even the nearly impossible to treat, Micro Satellite Stable MSS Tumor Typical cancers. It impedes the development of a collateral blood supply to tumors thereby starving and suffocating these tumors to death. It prevents the passage of metastatic cells into the blood supply therefore, metastasis is prevented. Leronlimab crosses the BBB, so it kills tumors which have metastasized to the brain; it also treats Glioblastoma Multiforme and Alzheimer's Disease. It crosses the Placenta, so near term infants may be protected against HIV via vertical transmission from the HIV infected mother. Leronlimab reduces fibrosis and scar tissue formation of any etiology and from any organ in the body, not only hepatic fibrosis, but also pulmonary fibrosis, cardiac fibrosis, renal fibrosis and on and on. The drug reduces inflammation all throughout the body, so it treats Long COVID together with Chronic Fatigue Syndrome. The drug is perfect for use in GVHD, Sepsis and is now being considered as a treatment in Stroke.

"CCR5 is expressed in over 95% of triple-negative breast cancers and influences breast cancer progression. In a murine model, Leronlimab prevented and reduced breast cancer metastasis suggesting a role for Leronlimab in the treatment of neoplasia. As CCR5 is central in inflammatory immune responses, it is currently being studied as a therapeutic for severe and critical SARS-CoV-2 infections and graft-versus-host disease (GVHD), where Leronlimab treatment reduced xeno-GVHD after HSCT of human cells to mice. Finally, Leronlimab is currently in phase 1 and 2 clinical studies to treat metastatic colorectal cancer, nonalcoholic Steatohepatitis, and long COVID after SARS-CoV-2 infection, demonstrating the diverse applicability of this safe and effective CCR5-targeting agent."

So, what is being rapidly discussed right here is not just one, two or even tens of disease entities. Literally, the drug can treat hundreds of disease entities. All with no side effects. Safely and Effectively.

Leronlimab is far different than all the other drugs because CCR5 is literally everywhere the immune system is, which is literally everywhere. Some drugs might somehow come close to emulating leronlimab, but, in truth, not very close at all. Really, none compare, even slightly. They realize they do not compare, and it becomes almost embarrassing to them how they don't hold a candle to its purview. Once leronlimab is unleashed, there shall be none else who might measure up to the newly created standard of drug excellence.

Let's try to understand. Those drugs have an important function, but do so by only speaking just one language. They do not speak universally, rather, they speak mono-lingually. All they are able to do is interact with their one receptor, like an "ear which can hear only one voice" and the outcome is always the same old predictable result. That's because what those drugs control are not in charge of running the entire immune system.

"Really, when Leronlimab binds to CCR5, it is blocking other ligands such as CCLigand5 from binding to CCReceptor5. G proteins are some of the components used by cells to perform some communication. When one cell wants to communicate with another cell, the cell that wants to speak, sends out a ligand, (its voice), and the cell that needs to hear, receives that ligand into its receptor, (its ear), and hears the "voice" of what the speaking cell said. Then, once heard, the hearing cell, sets off a chemical cascade within itself to accomplish what the speaking cell requested. That functionality of what the cell performs in response to obeying or listening to the request of the speaking cell varies based on the type of cell the hearing cell is. It may be a liver cell, a pancreas cell, an intestinal cell. It may be a neurological cell or an Immune cell. It may be a white blood cell of either the Innate or the Adaptive Immune system.

Well, respective to CytoDyn and to Leronlimab, CCL5 aka, RANTES is the voice of disease. Diseased cells like cancer, metastasis, tumor, all speak the mantra of CCL5 in a loud, blasting, dinnish format to the Innate and Adaptive Immune cells such as the Natural Killer Cells, the CD8 CytoToxic Killer T cells and to the T regulator and suppressor cells. When the cancer tumor cells chant the language of RANTES, the immune system gets confounded, deluded and confused. When RANTES binds completely to all the CCR5 receptors on the surfaces of these immune cells in mass, somehow, even these same G protein CCR5 receptors with RANTES bound to them get internalized into the inside of the immune cells and the inner cellular communication inside the cell just stops. The cells stop working. They stop functioning or they work for the tumor instead of killing it. They stop doing their immune, function of defending the human being. Rather, they either play dead and do nothing or begin defending the tumor and building up defenses and frameworks along with blood supply and nutrition for the tumor. Not only do they become paralyzed cells, but they have become deceived by RANTES to work and coexist on behalf of the tumor. Why? RANTES bound to their G Protein CCR5 and cells became confounded.

What I found to be unbelievable was when Leronlimab was introduced into a tumor environment, Leronlimab had a much stronger affinity for the G Protein CCR5 and displaced RANTES out from its binding site and replaced that binding site with itself. After the addition of Leronlimab, normal quantities of CCR5 G protein receptors popped up on the surfaces of the Immune Cells and the Immune cells begin functioning once again, the way they were meant to function. RANTES or CCL5, could no longer bind to CCR5 because Leronlimab bound with more affinity and Leronlimab kept the cells operating the way they should, for the patient, against the tumor and against metastasis."

Sometimes, the simple language which they speak are shared by only a few different diseases, but the language itself doesn't change, it is always the same. In such cases, speaking that language alters the course of those few diseases. Distant lands, distant states, oblivious to those words, those rulings, are still effected due to the consequences incurred of altering that specific language within the entire body. They falsely believe they are insulated by isolating their work to one small part, but in fact, they alienate and what results is a loss of function.

In stark contrast, the CCR5 receptor resides at the heart of ImmunoRegulation and Communication. At the base, at the origin. Since leronlimab is designed to 100% block CCR5, therefore, it secondarily blocks the CCL5 ligand, aka RANTES. This means that leronlimab blocks the distortion of the immunocellular communication and immunoregulation effected by RANTES directly at the origin of communication.

"On the other hand, the moment either the tumor finds a way to hide from these cells or your body's, or the tumor causes these cells to be suppressed. And that's why I call this the suppressor cells. And there are certain cells in your body called Treg cells or myelo-derived suppressor cells MDSCs, they use all technical, that when they get upregulated, you've lost your protection. And so the question then is, how do we understand this balance? How do we increase the killers, and how do we decrease the suppressors? "

Leronlimab blocks this distortion square at the base and heart of each and every biochemical cellular language. There are hundreds if not thousands of these biochemical languages. This means that leronlimab speaks all of these languages by binding to CCR5 better than RANTES. When leronlimab is present, it displaces RANTES from CCR5, and all the languages that RANTES speaks over are again restored and returned back their freedom to speak and power to enact and function as per their original design. They no longer are artificially controlled by the hypnotizing din of RANTES.

Leronlimab acts as an immunomodulator. Some of these cellular languages are strengthened while others are weakened by the effect of its presence. Its overarching, main effect is upon RANTES. RANTES, profusely produced and disseminated by the tumor is the primary voice of the tumor.

"And so I named the thing Quantum Oncotherapeutics just to be controversial so that doctors could understand what I'm talking about is that we need to understand the fact that you have a killer T cell and you have a killer suppressor cell. We have an M1 macrophage that actually chumps things up and M2 macrophage that blocks that. You have an NK cell that kills, an NK cell that inhibits. And we need to have that balance. Otherwise, you'll get into autoimmune disease. But there's a thing called quantum entanglement that is this cat alive or is this cat dead? If somebody interacts with that, and the person that interacts with that is the doctor. So you, as a doctor, could either be enlightened enough to activate just the activators and suppressors, suppressors and change the dynamic towards the cure. But it's very complex because it's now quantum because all those changes are happening in minutes in your body. These molecules, like God's particle, where they're colliding with each other and cells are colliding and interacting, happens within minutes. So you need to have a theory of how you interact at that level. And in so doing, the first thing you need to understand is how does cancer happen, and then how does it grow? How do you stop it?



EVERYTHING WE ARE DOING IS ACTIVATING THE SUPPRESSOR CELLS

PSS 014:01: This idea of a vaccine, a cancer vaccine, do you radiate that cancer? Do you remove that cancer? Do you remove the lymph nodes? Do you give chemotherapy? And crazy enough, over the last fifty years, I figured out that everything we're doing is not the word wrong because that's a bad statement, a pejorative statement. It's not enlightened, a better way to say it. Because everything we're doing is tipping the scales towards the suppressor cells. We're activating the suppressor cells. We're not activating the killing cells. And we can go into this conversation where I can explain that. So the key system which you just said is cancer is all about the immune system. So if you activate the immunosuppression system, you get more cancer. So then the fundamental root cause is what's activating that immune system on the other way. Yes. And that's inflammation."

RANTES induces severe suppression of the immune system which would otherwise fight the tumor. RANTES is found in great density in the vicinity of the tumor, in the Tumor Micro Environment because the tumor itself produces RANTES and voices it to all surrounding ears. When heard, it is especially effective in weakening and suppressing the immune system against cancer. RANTES turns the privates, sergeants, lieutenants, captains, majors, colonels and generals of the Immune System's Army, Navy, Air Force and Marine Corps into suppressed T-regulator cells and MDSCs which actually guard and protect the tumor against the attacks of the body.

"Cancer can not hide. Cancer can not deceive. Cancer can not trick. Cancer can not fool the immune system, the macrophages, the Cytotoxic killer T-cells, the Natural Killer cells, the dendrites. No, all remain alert when LL is present. They do not become zombies when RANTES binds, but they become who they were designed to be, the army, navy, air force, marines and coast guard of our immune system."

CCL5 / RANTES is the voice of the tumor as it shouts all around it, to all its neighboring vicinities, "I'm self, Protect me!". The tumor exudes RANTES and Natural Killer Cells NKCs immediately become slaves for the tumor's survival. None of the drugs discussed above target CCR5 or CCL5 aside from leronlimab. Maraviroc does it but not nearly as well as leronlimab. At maximum, Maraviroc achieves only about 80% CCR5 Receptor Occupancy.

"The novel strategies that Sacha develops shall contain leronlimab, because the novel drug does need to contain a CCR5 blockade which operates at 100% R.O. so as to prevent the reformation of any HIV Reservoir. No less than 100% R.O. would be suitable, so maraviroc would not suffice here as it has somewhere only around 78% R.O."

Pharmacology is currently scrambled because there is a separate drug for the vast number of different languages. No drug exists that can speak all the languages. No interpreter or translator exists until now. Leronlimab does speak all these cellular languages because the receptor it blocks holds the keys to every language. CCR5 lies at the heart of all biochemical cellular communication. RANTES has that key, but tumors and disease alike abuse its use and control by inducing cultism, a zombi like following, a slaveship of tumors and disease through the use of hypnotism and a drinking of the grape juice. Leronlimab annuls RANTES' voice and restores the normal functioning and awareness of the immune system.

There exists a multitude of CCR5 receptors on nearly every bodily organ, so therefore, CCR5 plays a massively important role on each of these organs in our bodies. CCR5 plays a huge part in the immunoregulation of nearly every bodily tissue. CCR5 plausibly plays what could be the most important function in nearly every Immune Cell in our bodies, because when occupied by RANTES, the Immune System in the local environment become completely suppressed.

"...they biopsied the colon of young people temporarily when no COVID to COVID and showed the persistence of replicating viruses in the colon tissue two years out. Replicating COVID viruses? Replicating COVID viruses. Replicating. Asymptomatic replicating in the tissue, meaning there's inflammation. And when you have this inflammation, these neutrophils, now getting geeky again, plasticize, flip from a protective neutrophil to a suppressive neutrophil. It's called an n two. It's called a myeloderived suppressor cell. That's official name. So now you have suppression in your body, and it's no wonder that then converts into colon cancer."

Leronlimab blocks CCR5, but in doing so, also blocks RANTES and displaces RANTES out of the CCR5 ear. When RANTES is blocked, the immune cells are no longer deceived by the tumors screams for assistance. Leronlimab plugs the ears such that the tumors cries for help are silenced. By doing so, leronlimab ensures that the fight goes on until the immune system wins the war against the tumor. It insures that none of the soldiers abandon the fight due to unwittingly becoming a slave of the enemy.

Once RANTES is heard by CCR5, the immune cells become zombies and no longer communicate with each other. They become tumor slaves. Their cellular communication becomes pro-tumor, not pro-body. They begin building a collateral blood supply to and from the tumor siphoning off the body's blood supply, so the tumor can eat and breathe. Instead of a militia for the body, the tumor converts them into a militia for the tumor as well as construction workers fabricating the necessary network and framework that ensures the tumor's survival. Instead of killing the tumor, they protect the tumor from any attack by hypnotizing and converting any would be killer cells into even more tumor slaves. These RANTES hypnotized T-Cells and NKCs actually change their allegiance and phenotype from M1 to M2, from killer T-Cells to T-Regulator Cells. But, with treatment, leronlimab becomes the voice of reason. Leronlimab dislodges RANTES from the CCR5 ear and further blocks RANTES from binding to and being heard by CCR5. Therefore, the deceiving commands of the RANTES language no longer are even heard when leronlimab is present, so the immune system remains the militia it was originally designed to be and eventually eradicates the tumor.

None of the drugs above listed above block CCL5 nor achieve what leronlimab can do. Even with the application of multiple drugs, where each one targets its own molecule, the same Immunomodulatory effect that leronlimab produces remains unachievable. The whole of those drugs together in combination do not measure up to the singular output of blocking CCR5 with leronlimab. When the combination of multiple drugs is attempted, especially when united together against leronlimab, they assuredly fail.

Therefore, as a result of its one mechanism of action in binding to CCR5 with even more affinity than its main ligand CCL5, leronlimab has a tremendous variety and a multitude of outcomes, none of which are directly measurable, because each outcome is immunomodulated, which is dependent upon the degree or state of the disease being addressed, combated and treated.

It seems as if CCR5 is a key to the disabling of the immune system, and many disease processes have access to that CCR5 key, namely RANTES. HIV, the Bubonic plague and when RANTES is produced by tumors, and many diseases like COVID, Influenza, then, the immune system may be compromised and even disabled. When leronlimab blocks the CCR5 ear, then the immune system is no longer disabled by RANTES and then can operate as it was originally designed without any interference.

Hopefully, we can move forward from this understanding. This drug is going EVERYWHERE. Even in its multiple forms, Long Acting leronlimab, leronlimab which crosses the placenta, leronlimab-PLS, and leronlimab which self-replicates, leronlimab-AAV, all forms do the same thing. They all block CCR5, but the question is for how long and that is how they differ.

So much research has been done regarding the blockade of CCR5 and the results of doing so in the multiple and various disease processes. Yet, this is all but ignored by Big Pharma who is all the more confident in their monolinguistic treatments. All of their confidence is placed in a variety of medications that can not and therefore, do not speak to each other. Instead of going after the real cause of the problem, which is the over-ruling complete disabling of the immune system, they preferably choose another path, not entirely obvious and simply have no regard to any possible consequence of that choice, and settle for even mediocre improvement. They choose not to re-engage the immune system, but rather accept its inability to defend the body, and design a work around. Then they repeat the process, with another drug, choosing yet another ill effective avenue. In each avenue, they speak, each their own language and only randomly work together in unison in a haphazard manner which either destroys or raises up. Each one uses its drugs for different purposes with nobody knowing for certain what the other is doing. Everything is performed in secret and the consequences of their use is yet unknown until it is not. Then, they will say, "we did not know that would happen" or "we were only trying to help".

On the other hand, leronlimab is not monolingual, but rather polylingual. It speaks every biochemical language of the body. Maybe the term ought to be panlingual. Our sheer confidence lies within a singular medication which speaks impartially to the entire body as a whole, which is neither compartmentalized nor separated by individual except of course to those with the delta 32 deletion mutation. The biochemical words, unfiltered, go everywhere, disseminated and distributed evenly to all the CCR5 ears within the entire body, thereby inducing the whole body to heal. The single, solitary drug is applicable for the whole host of disease processes. A variety or combination of drugs are not necessary. Leronlimab by its lonesome is all that is necessary because it sets the tone, the milieu, the environment where the immune system can do its job and heal the body. Leronlimab, because it re-engages the immune system, thereby enables each and every organ system, to communicate with each other, uninterrupted, even in their own separate language, because it enables the interpretation of the conversation, as it speaks every language, by freeing the immune system of the hypnotizing effects of RANTES. With leronlimab on board, nothing is a secret. Every organ system knows exactly what is happening in the other organ system next door and across the street, because, that is how it was originally designed, and leronlimab simply restores the balance before the disease came in, invaded and flipped things on its head.

Big Pharma instinctively believes you can achieve the sought after health we all seek through a vast variety and multitude of failing treatments. Leronlimab says, it is done and finished in one full swoop. BP wants to treat, over and over, with yet ever more increasingly powerful drugs, by blocking or augmenting even more refined and defined pathways, but yet ignoring the root cause of all disease, which is the disabling of the immune system.

"So if you really think about what the cause of cancer is, you know, and I did a piece with Sanjay Gupta many, many years ago on sixty Minutes. And I said, you know, the cause of cancer is its inability. It's not the rapidity of its growth, but its inability to die. And its inability to die is because it either hides from the cells that are matter, I. E. Your natural killer cells or your t cells, or and this is what I'm really worried about. Your body and the cancer has found a way to suppress your killer cells. And once they do that, once they activate what are called the suppressor cells, and you call yourself immunosuppressed, and then I think you see this rapid progression because there's nothing stopping it."

On the other hand, with one definitive treatment of leronlimab, the disease, in its entirety may be swept away indefinitely. Big Pharma gets around this by extending the half life of their disease sparing and prolonging drugs. This way they reduce quantity of treatments while extending duration of disease. Treatments then become necessary every 6 months instead of weekly, but by making such changes, they increase the progression of disease if their continued treatments are missed. Their drugs remain a treatment, because they do not eradicate the problem at its root. The disease always comes back and sometimes returns with a vengeance. They purposely permit the disease to sit and ruminate for the medications to wear off so it may re-emerge and re-infect. They hope that by treating more and more, even repeatedly with the same symptom treating medications, that eventually, the disease itself becomes too fatigued to fight back anymore and eventually dies off. This doesn't ever happen, but the idea is pushed unto the masses.

Each separate drug, possessing its own separate purpose, with a sufficient number of treatments, eventually could lead to health or if possibly combined with yet another treatment, which speaks yet another language, could bring about health. This is their mentality. Their hope. Their ideology. How flawed. Yet, if you disagree, you become disparaged. Punished to the nth degree if you disagree. If you refuse to give allegiance to their theocracy. Look at what has damn near happened to CytoDyn. Yet, the masses are forever forced to flock unto their medications only for a few extra months of suffering, forever hopeful and persistently begging for complete healing which never, ever comes, while leronlimab sits waiting, deep frozen in sub-zero, cryo-refrigeration, and maintained duly far enough away from their dying, helpless grasps. All power to BP, who prolong disease suffering by lengthening their disease treatment protocols.

https://talkmarkets.com/content/stocks--equities/when-penny-stocks-can-become-compelling-a-long-term-buy-with-cydy?post=489422


When Penny Stocks Can Become Compelling: A Long-Term Buy With CYDY
By James Gornick
Thursday, April 3, 2025 8:19 PM EDT


Introduction

CytoDyn Inc. (CYDY) is a clinical-stage biotechnology company developing leronlimab (PRO 140), a humanized monoclonal antibody targeting the CCR5 receptor. Leronlimab is being explored in multiple therapeutic areas, including HIV, immunology (graft-versus-host disease), and oncology. One of the key oncology targets for leronlimab is metastatic triple-negative breast cancer (mTNBC) – an aggressive breast cancer subtype with limited treatment options and poor prognosis. This report provides a detailed investigation of CytoDyn’s progress in advancing leronlimab for mTNBC, focusing on regulatory designations (Fast Track and Orphan Drug status) and clinical developments. It also evaluates CytoDyn’s financial and investment outlook for late 2025 through mid-2026, including stock performance, revenue projections, and R&D expenditures. Furthermore, a comparative analysis of competing therapies and companies in the mTNBC space is presented to gauge CytoDyn’s market positioning and the competitive landscape. Finally, we examine CytoDyn’s strategic projects and expenditure across North America and Europe, detailing how resources are allocated and potential impacts on the company’s growth trajectory.



Leronlimab in mTNBC: FDA Fast Track and Orphan Drug Designations

Fast Track Status: Leronlimab has received Fast Track designation from the U.S. FDA for mTNBC. In May 2019, the FDA granted Fast Track status to leronlimab (a CCR5 antagonist) in combination with carboplatin for treating patients with CCR5-positive metastatic triple-negative breast cancer. This designation, aimed at expediting the development and review of drugs for serious conditions with unmet needs, recognized the promising preclinical results of leronlimab in TNBC. Notably, murine models showed that CCR5 blockade dramatically reduced breast cancer metastasis (up to 98% reduction in tumor spread in a 6-week xenograft study). Fast Track status has enabled CytoDyn to engage in more frequent FDA communications and to submit parts of a Biologics License Application (BLA) on a rolling basis when ready. It signifies regulatory acknowledgment of leronlimab’s potential in TNBC but is not an approval; CytoDyn must still demonstrate efficacy and safety in clinical trials to achieve marketing authorization.



Orphan Drug Status: CytoDyn has also pursued Orphan Drug designation for leronlimab in mTNBC, although the outcome is nuanced. Triple-negative breast cancer, especially in metastatic form, is a serious disease but not very common as a subset of breast cancer, potentially qualifying it as a rare disease. In 2018, CytoDyn announced it had filed for Orphan Drug designation for mTNBC on the strength of compelling preclinical metastasis data. However, to date the FDA’s granted orphan designations for leronlimab have been in other indications – leronlimab has FDA Orphan Drug designation for prevention of graft-versus-host disease (GvHD). It is not publicly confirmed that orphan status was granted for TNBC, suggesting the application may still be under review or was not approved. (Triple-negative breast cancer may exceed the prevalence threshold for orphan status unless a specific subset is defined.) CytoDyn’s pursuit of orphan designation underscores its strategy to leverage incentives (e.g. tax credits, market exclusivity) for developing leronlimab in niche populations. Even without a formal orphan label in TNBC, Fast Track and potentially future Breakthrough Therapy designations remain key regulatory assets. In fact, following positive interim efficacy signals, the FDA encouraged CytoDyn to request a Breakthrough Therapy meeting, and CytoDyn submitted a Breakthrough Therapy Designation (BTD) application for leronlimab in mTNBC in late 2021. The BTD request was based on pooled Phase 1/2 and compassionate use data showing meaningful survival benefits (details below). While BTD is still pending (not yet granted as of the latest updates), the pursuit highlights progress toward potentially accelerated approval pathways if ongoing and planned trials confirm the early promise.



Clinical Progress in Metastatic Triple-Negative Breast Cancer

Trial Developments: CytoDyn’s clinical program in mTNBC has progressed through early-phase studies, showing encouraging signals. An initial Phase Ib/II trial (NCT03838367) evaluated leronlimab with carboplatin in CCR5+ mTNBC patients. By pooling results from that trial, an expanded compassionate use program, and a small basket trial, CytoDyn analyzed outcomes for 28 women with stage IV TNBC who received leronlimab alongside standard chemotherapy. All patients were heavily pre-treated (having failed ≥2 prior systemic therapies), and many had aggressive disease (61% had visceral metastases and 21% had brain metastases at baseline). The findings, reported in late 2021, were notable:

• Overall Survival (OS): Patients given higher dose leronlimab (525 mg or 700 mg weekly) plus chemotherapy achieved a median OS of 12+ months, exceeding historical outcomes with standard chemo (~6.6 months) and appearing slightly longer even than the benchmark of 11.8 months OS with sacituzumab govitecan (Trodelvy). (Trodelvy is an FDA-approved antibody-drug conjugate for mTNBC after ≥2 prior treatments, which had received its own Fast Track and Breakthrough designations.) In the subset who received leronlimab + carboplatin specifically, median OS was also 12+ months. By comparison, Trodelvy’s phase III trial OS was 11.8 months and standard single-agent chemo ~6–7 months, highlighting a potentially meaningful survival benefit for leronlimab-combination therapy.

• Progression-Free Survival (PFS): High-dose leronlimab plus chemo yielded a median PFS of 6.2 months, significantly longer than historical controls (˜2.3 months on chemo alone, and 4.8 months with Trodelvy). This suggests leronlimab may delay disease progression when added to treatment.

• Tumor Response and Disease Control: Among 12 evaluable patients with measurable lesions on PET/CT, 92% achieved disease control (stable disease or partial response) after starting leronlimab; 25% had partial responses and 67% had stable disease, with only one patient (8%) progressing at first assessment. Such disease control rate is promising in refractory mTNBC. Additionally, a circulating tumor cell (CTC) biomarker analysis (LifeTracDx™) indicated that patients whose CTC and CAML (cancer-associated macrophage-like cell) counts decreased on therapy were the ones showing clinical improvement. This not only validates leronlimab’s anti-metastatic mechanism (targeting CCR5 on tumor cells and the tumor microenvironment) but could provide a way to identify responders early.

These results, albeit from a small non-randomized dataset, signaled that leronlimab may improve survival in mTNBC, potentially rivaling existing third-line therapies. The FDA’s Fast Track designation was granted on the strength of earlier preclinical data, and these human data encouraged CytoDyn to seek Breakthrough designation. While a definitive Phase III trial is needed for approval, CytoDyn’s management has indicated that if further data remain positive, they could explore accelerated approval for mTNBC. Notably, the FDA has suggested that with compelling interim results, a regulatory filing could be considered sooner, especially given the dire outcomes in this patient population.

Current Status and Next Steps: As of early 2025, CytoDyn is consolidating and building upon these oncology findings. After resolving a legal dispute with its former CRO (which had delayed data access), the company recently updated the survival status of patients from the mTNBC trials. In a February 2025 announcement, CytoDyn reported remarkable long-term survivors among leronlimab-treated mTNBC patients – some patients who had exhausted prior treatments survived beyond 36 months with no evidence of active disease. These anecdotal but striking outcomes have been compiled into an abstract submitted to the ESMO Breast Cancer conference (Europe) in May 2025 for peer review. The implication is that a subset of mTNBC patients may achieve prolonged remission on leronlimab, which, if validated, would be paradigm-shifting in a cancer known for rapid progression.

To further strengthen the case for leronlimab in TNBC, CytoDyn is initiating new preclinical studies of combination therapies. Two investigator-sponsored studies will examine leronlimab in combination with: (1) sacituzumab govitecan (Trodelvy), the ADC therapy, and (2) pembrolizumab (Keytruda), an immune checkpoint inhibitor. The goal is to explore synergistic effects – for example, whether adding leronlimab can enhance the efficacy of these approved treatments. Such combinations make scientific sense: Trodelvy delivers cytotoxic payload to kill tumor cells, potentially releasing antigens and inflammatory signals, while leronlimab could prevent the resultant inflammatory tumor microenvironment from spurring further metastasis (CCR5 is implicated in metastasis and tumor immunosuppression). Likewise, CCR5 blockade might augment immunotherapy (Keytruda) by modulating immune cell trafficking. Results from these studies will guide the design of the next clinical trial in TNBC – likely a more definitive Phase II/III study testing leronlimab with standard therapy in a controlled setting.

It’s worth noting that CytoDyn’s oncology focus had been somewhat on hold during a corporate transition period in 2022–2023 when the company faced FDA clinical holds and management changes. The FDA placed a partial clinical hold on leronlimab in March 2022 (due to manufacturing/quality and safety data issues) which affected trials in HIV and halted COVID-19 studies. This hold indirectly slowed oncological progress as well. However, in March 2024 the FDA lifted the clinical hold on leronlimab, signaling that CytoDyn satisfactorily addressed the agency’s concerns. With the hold resolved, CytoDyn is now free to “return to the clinic” and has renewed momentum in its trials. The company’s CEO (appointed Nov 2023) emphasized that getting the hold lifted, publishing pending data, and advancing new trials were top priorities – all of which have seen progress.

In summary, leronlimab’s development in mTNBC is progressing on both regulatory and scientific fronts. It holds Fast Track status and has produced encouraging Phase 1/2 results that led to a Breakthrough designation application. Upcoming milestones likely include presenting mature data (ESMO 2025), launching a follow-up trial (potentially Phase II/III in late 2025), and if data are strong, seeking accelerated approval or a partner to support a Phase III. CytoDyn’s ability to realize FDA approval will depend on confirming these early survival gains in a larger patient population.



Financial Performance and Investment Outlook (Q4 2025 – Q2 2026)

Historical and Current Stock Performance

CytoDyn’s stock has historically been volatile, reflecting its high-risk, developmental stage status. Prior to 2020, CYDY traded below $1 per share and was relatively under the radar. During the early COVID-19 pandemic, however, CytoDyn garnered intense investor attention by attempting to repurpose leronlimab for severe COVID-19. Behind a wave of publicity and speculation, the stock surged to an all-time high of $10.01 by June 30, 2020. This meteoric rise (a >10-fold jump) was fueled by hopes that leronlimab could be a COVID treatment and rumors (later debunked) that it might be part of the U.S. government’s Operation Warp Speed. The rally proved short-lived: as clinical testing failed to show clear benefit in COVID-19 and questions arose about the company’s promotional tactics, shares tumbled back down, trading near $2 by mid-2021. In subsequent years, the stock continued to decline amid regulatory setbacks – by late 2022, after the FDA imposed clinical holds and CytoDyn’s CEO was replaced, CYDY traded in the pennies (well under $1 again). Heavy dilution of the share count over time has also weighed on the stock price. For instance, shares outstanding roughly doubled from ~570 million in 2020 to over 1.2 billion by 2025, as the company issued equity to raise capital.

As of early 2025, CytoDyn’s stock remains a penny-stock but has shown recent signs of recovery. On February 24, 2025, CYDY closed at $0.35 per share (up ~17% that day), with a market capitalization of about $439 million (1.23 billion shares outstanding). This uptick coincided with the positive mTNBC survival news and general optimism following the FDA hold lift. The stock has logged several consecutive days of gains, indicating renewed investor confidence or speculative interest ahead of anticipated oncological developments. Still, at $0.75 $1.40, the price reflects a cautious valuation given the company’s lack of revenue and need for further trial success. It’s also significantly below peaks, illustrating the risks investors have priced in (e.g. past clinical disappointments and financing needs). The historical peak of $10/share in 2020 was clearly an anomaly driven by pandemic hype, and current levels are more grounded in the slow path of drug development.

Looking forward into Q4 2025 – Q2 2026, CytoDyn’s stock performance will hinge on key catalysts and milestones:

• Clinical Data & Conferences: If the ESMO 2025 presentation of mTNBC data is well-received (Q2 2025 event) and if CytoDyn initiates a new Phase II/III trial by late 2025, positive momentum could carry into the stock. Any signals of efficacy confirmation or trial expansion could drive speculative runs. Conversely, delays or lackluster data would dampen investor enthusiasm.

• Regulatory Decisions: A potential Breakthrough Therapy designation grant in 2025 would be seen as a strong positive, possibly boosting share price. On the other hand, if the FDA declines BTD or if interim data do not support an accelerated approval plan, the stock might stagnate. Additionally, CytoDyn’s other program in HIV could see developments – the partial clinical hold on the HIV program was lifted in Feb 2024, and the company may re-file its HIV BLA or start a new HIV trial. Any progress toward approval in HIV (e.g., BLA resubmission by 2025) could significantly rerate the stock upwards, given that HIV was originally the lead indication for leronlimab.

• Financing and Listing Status: CytoDyn will likely need to raise additional capital to fund Phase II/III trials through 2026. The company’s ability to secure non-dilutive funding or partnerships (discussed below) versus issuing more shares will impact stock performance. If heavy dilution continues, it could suppress share price despite clinical progress. Conversely, landing a partnership deal (e.g. licensing leronlimab rights in a region or indication) could provide funding relief and be viewed favorably by investors. CytoDyn currently trades over the counter; any efforts to up-list to a major exchange (or regain NASDAQ listing if attempted) by meeting price and governance criteria would also influence investor perception.

Overall, the investment outlook for Q4 2025 – Q2 2026 is cautiously optimistic but volatile. CytoDyn is essentially at a pivotal stage – it has a promising asset and upcoming trials, but also a history of setbacks. Successful execution of its 2025 clinical plans (especially in oncology) could “make 2025 a pivotal year for the Company,” as the CEO stated. This could translate into significant stock appreciation in 2026 if a clear path to an approval or major partnership emerges. However, the downside risks (scientific failure, funding shortfalls) remain high, meaning the stock may continue to trade on speculative swings. Investors are likely to watch each milestone closely, and we can expect price volatility around data releases and financial announcements.



Revenue and Earnings Forecasts

As a development-stage biotech, CytoDyn has not generated product revenue to date. The company has no approved products on the market, and thus no sales or licensing revenue as of FY2024. All operations have been funded by external financing (equity and debt) since inception. In its latest annual report, CytoDyn explicitly states: “We have not generated revenue from product sales, licensing, or other income opportunities to date. Since our inception, we have incurred operating losses each year…”. This pattern is expected to continue for the foreseeable future, at least until FDA approval allows commercialization.

Near-term revenue forecasts (Q4 2025 – Q2 2026) remain effectively zero, given that leronlimab would unlikely be approved and launched by that time. The earliest scenario for revenue would be if CytoDyn were to license out leronlimab or partner on a regional basis, yielding upfront payments. Management has indicated they are exploring licensing deals for certain indications to bring in non-dilutive funds. For example, a partnership for HIV or cancer could involve milestone payments. However, unless such a deal materializes, analysts do not project meaningful revenue in 2025 or early 2026. Even with an optimistic timeline, approval for mTNBC or HIV could come in late 2026 or 2027, which means commercial sales would start beyond Q2 2026.

That said, investors may start to price in future revenue potential if late-2025 clinical results are strong. Sell-side analyses (where available for OTC stocks) often model peak sales for leronlimab in various indications. For instance, the HIV combination therapy market or a TNBC niche could each represent several hundred million dollars annually in peak sales if leronlimab succeeds. There is also an upside in multiple indications (oncology, HIV, immunology), which could cumulatively reach blockbuster revenue in a best-case scenario. But such outcomes are speculative at this stage. In the absence of concrete revenue, CytoDyn’s quarterly “financials” through early 2026 will continue to show net losses, with any one-time licensing or legal settlement gains being the only boosts. (Notably, in 2023 CytoDyn won a legal settlement against its former CRO, yielding a $12 million cash payment and cancelation of $14 million in payables. This was reflected in improved finances in FY2024 but is a non-recurring event.)

Earnings per share (EPS) will likely remain negative through Q2 2026. The magnitude of losses may shrink if the company curtails expenses or finds partners but will expand if they self-fund a large Phase III trial. Investors should be prepared for continuing net losses and cash burns until at least one product approval or major partnership.



R&D Expenditures and Financial Health

Research & Development (R&D) Spending: CytoDyn’s R&D expenditure has fluctuated significantly over the past few years, reflecting the company’s shifting focus and resource constraints. In the fiscal year ended May 31, 2021 – at the height of CytoDyn’s multi-indication push (HIV BLA filing, multiple COVID trials, and oncology trials all ongoing) – R&D spend was very high. FY2021 R&D expenses totaled approximately $58.4 million, an ~11% increase over the prior year. This heavy spending was due to late-stage trials and manufacturing scale-up (e.g. costs of a Phase 3 HIV trial and COVID Phase 2/3 trials, as well as preparing biologics manufacturing with partners like Samsung). In FY2022, after the COVID trials and certain programs wound down, R&D expenses dropped to about $27.0 million. The reduction continued drastically into FY2023, when CytoDyn was largely in a holding pattern due to the FDA clinical hold and funding issues – R&D spend in FY2023 was only $2.6 million. Essentially, many R&D activities were paused in 2022–2023, and some prior expenses were even reversed (for example, CytoDyn had a credit in “Clinical” category in 2023, likely due to recovering costs or over-accruals).

In the most recent year, FY2024, R&D investment rebounded to about $7.2 million. The breakdown shows CytoDyn ramped up spending on manufacturing (CMC) and preparing new trials: of the $7.24M, about $3.87M went to CMC (up 129% from prior year), $1.9M to clinical trial costs (compared to effectively $0 in 2023), and nearly $1M to patents/licenses. This indicates that by late 2023 and early 2024, the company was preparing to restart clinical development, investing in drug production and trial startup for oncology and perhaps an inflammation study. Going forward, we can expect R&D expenditures to climb as CytoDyn progresses its pipeline. Initiating a Phase II colorectal cancer trial and a potential Phase II inflammation trial in 2024 will incur new costs. If a Phase IIb/III TNBC trial begins in 2025, that would significantly increase R&D spending through 2026. Thus, for the outlook period:

• FY2025 (ending May 2025) R&D might increase substantially from FY2024’s $7M, possibly into the mid-teens of millions, given trial launches and ongoing preclinical projects.

• FY2026 could see R&D spending grow further if multiple trials are fully underway (potentially $20M+ range, albeit still modest compared to larger biotech companies).

Financial Resources and Cash Burn: CytoDyn’s net losses have historically been large due to operating expenses and interest in debt. In FY2023, the net loss was $79.8 million, which improved to $49.8 million net loss in FY2024 (the improvement partly thanks to the $12M legal settlement and cost-cutting). The company has taken steps to reduce General & Administrative (G&A) costs – e.g., cutting headcount and legal fees related to past investigations. G&A decreases in FY2024 indicate a leaner operation focusing resources on core R&D. The CEO stated in Dec 2024 that CytoDyn has “sufficient cash and drug supplies on hand to complete its clinical priorities in 2025.” This suggests that recent financings plus the Amarex settlement have bolstered their cash position enough to fund the planned trials through at least mid-2025. The settlement with Amarex not only provided $12M cash (with $10M upfront) but also eliminated a $14M debt from the balance sheet, significantly improving liquidity. Additionally, CytoDyn reclaimed about $6.5M in previously restricted cash related to the Amarex case.

Despite these improvements, CytoDyn will likely require further funding in late 2025 or 2026. The cash burn (operating loss plus debt servicing) will continue, and currently the company relies on issuing equity or convertible notes. Investors should monitor the company’s financing announcements: an equity raise could dilute shares (the share count has ballooned above 1.2 billion), whereas a partnership deal could infuse capital without as much dilution. The investment outlook through Q2 2026 must account for this financing risk. Positive developments in the clinic could ease fundraising – for example, strong Phase II data might attract a licensing partner or allow a strategic investment at a higher share price. The CEO has expressed optimism that the current strategy will unlock significant shareholder value and potentially allow non-dilutive opportunities. If those materialize, the financial overhang will lessen. Conversely, in a bearish scenario where trial results disappoint or capital markets tighten, CytoDyn might face a cash crunch and be forced to issue shares at a low price or cut back programs, which would hurt the investment thesis for 2025–2026.

In conclusion, CytoDyn’s financial health is stabilizing but remains that of a development-stage biotech: no revenue, ongoing losses, and reliance on external funding. Key financial indicators to watch through 2026 include the R&D spend trajectory (as a marker of pipeline progress), the company’s cash balance/runway, and any revenue-like inflows from partnerships. The investment outlook is highly event-driven – significant scientific or regulatory milestones in the next 4–6 quarters have the potential to markedly improve CytoDyn’s valuation (as seen by the stock’s responsiveness to news), while setbacks could exacerbate dilution and delay any potential profitability beyond the forecast horizon.



Competitive Landscape: mTNBC Therapies and Market Positioning

Metastatic triple-negative breast cancer is a fiercely competitive and fast-evolving therapeutic area, despite being a relatively niche subset of breast cancer. Any company developing a new mTNBC therapy must contend with existing treatments and numerous pipeline agents from both large pharmaceutical players and smaller biotechs. Below we compare leronlimab and CytoDyn’s strategy with key competing therapies and companies in the mTNBC space, evaluating market positioning, potential threats, and opportunities:



Current Approved Therapies for mTNBC:

• Chemotherapy (Standard of Care): For years, the backbone of mTNBC treatment was cytotoxic chemotherapy (e.g. taxanes, anthracyclines, platinum agents). While chemo has response activity, mTNBC often relapses quickly. Median overall survival on single-agent chemo in refractory mTNBC is only ~6 months. Leronlimab is being developed on top of chemotherapy (e.g. with carboplatin), aiming to improve on this low baseline. If leronlimab continues to show that adding it can roughly double OS compared to chemo alone (12+ vs ~6 months) , it could carve out a role as a chemo-sensitizer or metastasis inhibitor adjunct to standard drugs.

• Immunotherapy (Checkpoint Inhibitors): Pembrolizumab (Keytruda, by Merck) is approved for first-line treatment of mTNBC in combination with chemo for tumors expressing PD-L1. In the Keytruda + chemo significantly improved outcomes in PD-L1 positive mTNBC, extending median survival to ~23 months vs ~16 months with chemo alone in that subset (and improving progression-free survival). This has made immunotherapy + chemo the standard 1st-line for ~40% of mTNBC patients (those with PD-L1≥10 by CPS score). Leronlimab, by contrast, is being explored primarily in later-line disease regardless of PD-L1 status. It may not directly compete with Keytruda in first line but could complement immunotherapy. Indeed, CytoDyn’s planned preclinical combination of leronlimab with pembrolizumab suggests a strategy to eventually move into earlier lines or PD-L1–negative patients, by enhancing immune response in those who don’t qualify for Keytruda now. Threat/Opportunity: Merck is a dominant player; if checkpoint blockade evolves (new checkpoints or combo regimens), it could raise the bar for new entrants. However, leronlimab’s unique mechanism (CCR5 blockade) might be synergistic with checkpoint inhibitors, potentially making it an attractive addition rather than a head-to-head competitor. This could be an opportunity for a partnership (e.g., if Merck or another big pharma sees value in adding CCR5 inhibition to their regimen).

• Targeted Therapy for BRCA-mutated TNBC: A small subset of mTNBC patients (~10%) have BRCA1/2 germline mutations. PARP inhibitors (olaparib, talazoparib) are approved for those patients and can provide benefit. This doesn’t directly overlap with leronlimab’s approach, as CCR5 targeting is agnostic to BRCA status. Leronlimab could theoretically be combined with PARP inhibitors too if needed. The PARP-treated population is limited and does not pose a major threat to leronlimab’s addressable market, but it reduces the pool of patients in later lines (BRCA-mutant patients might use PARP first, delaying other options).

• Antibody-Drug Conjugate (ADC) Therapy: Perhaps the most significant competitor to leronlimab in the post-chemotherapy setting is Gilead Sciences’ sacituzumab govitecan, brand name Trodelvy. Trodelvy is an ADC that delivers a toxic payload to Trop-2 expressing tumor cells. It was granted accelerated FDA approval in April 2020 for mTNBC after ≥2 prior therapies and converted to full approval in 2021 after confirmatory data. In its phase III ASCENT trial, Trodelvy improved median OS to 11.8 months vs ~6-7 months for chemo in refractory mTNBC and had a median PFS of 4.8 months vs ~1.7 months on chemo. This positioned Trodelvy as a standard 3rd-line option, and it has quickly been adopted in guidelines. Trodelvy’s success underscores how high the stakes are: it sets a new benchmark in a setting where leronlimab also seeks to demonstrate benefit. Comparison: The data CytoDyn has reported suggest leronlimab+chemo might achieve similar or slightly better efficacy than Trodelvy (OS ~12+ months; PFS ~6.2 months). Importantly, some patients on leronlimab had brain metastases (21% of the cohort) and still achieved those outcomes, whereas Trodelvy’s trial included only 12% with brain mets. If leronlimab can confirm these outcomes in a larger trial, it could potentially compete with Trodelvy or even be used in combination with it. CytoDyn is testing synergy with Trodelvy preclinically, hinting at a vision where a CCR5 blocker might be added to ADC therapy to further extend survival or prevent metastatic spread to brain/bone. However, Trodelvy’s major advantage is that it’s already approved and, on the market, worldwide (Gilead is also expanding Trodelvy to earlier lines and other cancers). Gilead’s large resources and oncology focus (they acquired Immunomedics for $21 billion to get Trodelvy) means they will vigorously defend that franchise. A potential threat is that by the time leronlimab is ready, next-generation ADCs could be on the scene: for example, AstraZeneca/Daiichi Sankyo’s datopotamab deruxtecan (another Trop-2 ADC) is in phase 3 trials for TNBC, and Seagen/Merck’s ladiratuzumab vedotin (an ADC targeting LIV-1) was in development via a partnership. These novel ADCs aim to further improve outcomes or move to earlier lines, which could shrink the unmet need in later-line TNBC. CytoDyn will need to position leronlimab either as combinatorial (making other therapies work better) or target a unique niche (e.g. patients with certain metastatic profiles, or those who cannot tolerate more toxic drugs). One opportunity is safety: leronlimab, being a targeted immunologic agent, has shown a favorable safety profile with lack of significant adverse events noted in trials. If it can be given long-term with minimal toxicity, it may be very useful as maintenance or add-on therapy, whereas ADCs and chemo have cumulative toxicities.

• Emerging Therapies: Beyond the big names, numerous smaller companies are exploring TNBC treatments: immune therapies (TIL cell therapies, cancer vaccines), targeted inhibitors (e.g. AKT inhibitors like ipatasertib – though one such trial failed), and other novel antibodies. While none has yet changed the standard of care, the field is crowded. For CytoDyn, a notable similar approach is CCR5 inhibition by other means. Maraviroc, a small-molecule CCR5 inhibitor (originally an HIV drug by Pfizer), showed some preclinical efficacy in cancer models, but no pharma has actively advanced it for TNBC. CytoDyn’s own preclinical work was inspired by maraviroc’s effects on metastasis, and so far, leronlimab is leading in this mechanism. Thus, direct competition on CCR5 is minimal. However, if leronlimab’s concept proves valid, larger firms might develop their own CCR5-targeting antibodies or small molecules.

Market Positioning of CytoDyn: CytoDyn is unique in focusing on metastasis prevention and immunomodulation via CCR5 blockade, whereas competitors mostly focus on killing tumors directly (chemotherapy, ADCs) or unleashing immune attack (checkpoints). Leronlimab’s potential use across diseases (HIV, cancer, inflammatory conditions) is a differentiator – success in one area could bolster the others. In mTNBC specifically, CytoDyn’s strategy might be to position leronlimab as an adjunct therapy to improve outcomes when added to existing regimens. This cooperative positioning could reduce competitive head-to-head clashes. For example, instead of replacing Trodelvy or Keytruda, leronlimab could be combined with them to yield incremental benefits (as their new studies propose). If that synergy is demonstrated, CytoDyn could partner with larger oncology companies (Merck, Gilead, etc.) to incorporate leronlimab into combo trials. This is both an opportunity (piggybacking on established drugs can accelerate adoption) and a threat (if the combos fail, leronlimab might have no standalone path).

Another aspect of market positioning is pricing and market size. TNBC is a smaller market than hormone-positive breast cancer, but therapies like Trodelvy have shown it can be lucrative – analysts projected Trodelvy to reach $4–5 billion in peak sales to justify its $21B acquisition price, factoring in expansion beyond TNBC. CytoDyn will likely seek Orphan drug-type pricing if leronlimab reaches market in TNBC (premium pricing for a rare, aggressive disease). However, payers will expect significant benefit given the cost of existing therapies. If leronlimab can show an overall survival benefit on par with or better than competitors, it will have a strong value proposition.

In terms of competitive threats, aside from therapeutic efficacy, CytoDyn faces competition for clinical trial enrollment and mindshare. Companies like Gilead, Merck, AstraZeneca are running numerous TNBC trials – CytoDyn will need to recruit patients for its future studies, which could be challenging if patients have other trial options. The company’s smaller size and resources mean it must execute trials efficiently to not fall behind. There is also the risk that any failure or safety issue in one CytoDyn program could spill over to others (for instance, if a safety signal emerged in HIV or another cancer, it could cloud the prospects in TNBC). Larger competitors usually have more buffers in that regard.

Potential Opportunities for CytoDyn: If leronlimab’s unique approach is validated, CytoDyn could fill an important gap in TNBC care: preventing or controlling metastasis. One intriguing angle is the long tail of survivors they observed – if a subset of patients achieves durable remission with leronlimab, it hints at a possibility of turning TNBC into a chronic disease or even curing some cases. No current therapy offers that in late-line TNBC. Establishing such a niche (perhaps treating minimal residual disease to prevent recurrence or metastasis) could make leronlimab an essential part of TNBC management. Additionally, leronlimab could secure multiple FDA designations (BTD, Orphan) for TNBC which confer market advantages like expedited review and potentially 7-year exclusivity if Orphan status is obtained. This would help CytoDyn compete against big pharma by extending its runway post-approval.

In summary, CytoDyn’s leronlimab faces stiff competition from both standard treatments (chemo) and advanced therapies (Trodelvy, Keytruda) in mTNBC. However, its mechanism of action is complementary, and early data suggest it can enhance outcomes beyond what current drugs achieve. The competitive landscape is both a validation (big investments by Gilead, Merck show the value of effective TNBC drugs) and a challenge (those companies set the efficacy bar and control market access). CytoDyn’s ability to thrive will depend on differentiating leronlimab’s clinical profile (safety, unique benefits) and possibly teaming up with larger players to integrate into combination regimens. If successful, leronlimab could become a valuable adjunct in TNBC therapy – an outcome that would not only benefit patients but also position CytoDyn strongly against its larger competitors.



Regulatory and Market Factors Impacting CytoDyn’s Trajectory

CytoDyn’s future is highly sensitive to various external factors beyond just clinical trial results. These include regulatory decisions, industry trends, and broader market conditions in biotech. Below we analyze the most relevant factors that could shape the company’s trajectory through 2025–2026:

Regulatory Approvals & Designations: The timeline and success of FDA approvals will be the single biggest factor for CytoDyn. The company is juggling multiple potential approval paths:

• In HIV, CytoDyn was on the cusp of filing for approval in 2019 (leveraging Fast Track to do a rolling BLA), but that effort faltered due to deficiencies in the application and the partial clinical hold in 2022. Now that the hold is lifted (2024) , CytoDyn may reinitiate its HIV program, possibly with a refined trial in a niche population (the May 2024 Shareholder Letter mentions a trial in HIV patients with immune dysfunction post stem-cell transplant as a “proof of cure” study) . If CytoDyn manages to resubmit the HIV BLA or gain approval for a smaller HIV indication by 2025–2026, that would dramatically alter its trajectory – providing the first revenue stream and validating its platform. However, the company must navigate lingering regulatory scrutiny; the FDA will likely require robust data and compliance given past issues. A failure to get HIV approval after years of effort would be a blow, whereas a successful approval (perhaps as combination therapy for multi-drug-resistant HIV) could greatly boost investor confidence.

• In Oncology (mTNBC), regulatory interactions will revolve around trial design and potential early approval pathways. Achieving Breakthrough Therapy Designation (still pending as of 2025) would facilitate more intensive FDA guidance on designing a pivotal trial. If leronlimab’s ongoing evidence impresses regulators, CytoDyn might attempt an accelerated approval based on a Phase II single-arm study (if outcomes are outstanding in a high unmet-need subset). This would be contingent on a confirmatory trial. The FDA will evaluate the totality of data – any missteps in trial execution or data integrity could slow progress. On the other hand, a supportive FDA (as implied by Fast Track and suggestion to seek BTD) could mean a smoother path. Additionally, CytoDyn might consider ex-U.S. regulatory strategies: for instance, seeking EMA approval or Conditional Marketing Authorization in Europe if data is compelling. To date, leronlimab has not announced EMA’s PRIME designation or similar, but as the program advances, engaging European regulators could open a parallel path. A factor here is Orphan Drug designation in regions: while U.S. orphan status for TNBC is uncertain, CytoDyn could seek EMA orphan designation for mTNBC if criteria are met, which would give 10 years of EU market exclusivity upon approval. Success or failure in obtaining these designations will impact CytoDyn’s competitive protection and attractiveness to partners.

Clinical Trial Developments & Timeline: The speed and outcome of CytoDyn’s ongoing/planned trials will strongly influence its trajectory. Any significant delays in trial enrollment or data readouts (due to competition for patients, operational issues, etc.) could push milestones beyond Q2 2026, which the market would view negatively. Conversely, if CytoDyn can quickly enroll and perhaps report interim results from a Phase II oncology trial by mid-2026, it could create positive momentum. The company’s new leadership and CRO partnerships aim to ensure trials are well-run: CytoDyn has engaged Syneos Health as CRO for its oncology trial in colorectal cancer and is presumably applying lessons from past CRO problems (the Amarex case) to avoid data mishandling. Achieving milestones on schedule – such as “first patient in” for trials, interim analyses, and completion of enrollment – will be important signals. A particular regulatory risk to watch is if any safety issues emerge in trials; CCR5 blockade has generally been well-tolerated (no serious drug-related adverse events in HIV trials), but broader use in cancer patients might reveal new effects. The company’s integrated safety analysis of ~1600 patients to date shows a favorable profile, which is reassuring. Maintaining that safety profile is crucial; a safety scare could lead to another clinical hold or require additional studies.



Industry and Market Trends:

The biotech sector’s condition between 2025 and 2026 will affect CytoDyn’s fortunes. A few macro factors include:

• Investment Climate: The ease of raising capital for small cap biotechs varies with market cycles. If the biotech sector is bullish (high investor appetite for risk, strong IPOs and financings) in late 2025, CytoDyn may find it easier to raise money at favorable terms or even uplist its stock. If a bearish or high-interest rate environment persists, funding could be scarce, forcing dilutive financings. CytoDyn’s cash runway must last through these cycles, or it should aim to secure a partnership to mitigate financing needs. The CEO has highlighted that “third parties interested in partnering” increased after the hold lift, which could be fortuitous if broader markets tighten – partnerships can provide capital independent of public markets.

• M&A and Partnerships in Oncology: The last few years saw major acquisitions (Gilead-Immunomedics for $21B, Merck’s deals with Seagen, Pfizer’s acquisition of Seagen in 2023, etc.) indicating big pharma’s hunger for oncology assets, especially in breast cancer. If leronlimab’s data continues to impress, CytoDyn could become a takeover or licensing target. An acquisition of CytoDyn by a larger company is a scenario that would dramatically change the investment outlook (often yielding a premium to shareholders). Even short of acquisition, a regional licensing deal (for example, a deal granting partner rights in Europe or Asia in exchange for upfront cash and milestones) could accelerate development in those regions and give CytoDyn funds to focus on North America. Global market factors, such as the size of the TNBC market in Asia/Europe, could drive such deals – mTNBC is an area of unmet need globally, so interest is not limited to the U.S.

• Competitive Approvals: If a competitor achieves a new approval in mTNBC between 2025–2026, it could impact CytoDyn. For instance, if datopotamab deruxtecan (Dato-DXd) reports positive Phase 3 results and gets FDA approved in 2025, it would become a direct competitor to Trodelvy (and indirectly to leronlimab’s niche). Alternatively, if a competitor’s trial fails, that could leave more room for leronlimab. CytoDyn must keep an eye on competitors’ timelines. Notably, Merck and AstraZeneca’s Phase 3 trials in TNBC are reading out in 2024–2025; positive results could entrench new standards of care. CytoDyn will need to design its Phase 3 (when it comes) such that it can demonstrate added benefit over whatever is standard at that future time. The clinical and regulatory bar is moving target – FDA’s approval of an effective new drug can raise the required comparator for subsequent trials.

Intellectual Property (IP) and Exclusivity: CytoDyn’s ability to secure its market will depend on patents and exclusivity periods. Leronlimab is a novel antibody, and CytoDyn has patents around its use in HIV and potentially cancer. The development of a long-acting formulation of leronlimab mentioned by the CEO is partly to extend patent life. Orphan Drug exclusivity (7 years U.S., 10 years EU) for any approved indication would be an asset to keep competitors (including biosimilars) at bay. If CytoDyn fails to get approvals before key patents expire, it could face biosimilar competition down the line (though that is beyond 2026 horizon). In the nearer term, IP doesn’t pose an obvious roadblock; rather, it’s a defensive factor that could enhance CytoDyn’s value if solid.

Legal and Governance Factors: CytoDyn has had a tumultuous past with legal issues – e.g., class-action shareholder lawsuits (alleging the former CEO made misleading claims about COVID), SEC and DOJ investigations into potential stock fraud, and the Amarex litigation. Many of these have been addressed: the Amarex lawsuit was settled favorably; the former CEO Nader Pourhassan was terminated in early 2022 and later indicted by the DOJ (in 2023) for alleged schemes to defraud investors. The resolution of these issues is largely positive for CytoDyn moving forward, as it can distance itself from past controversies. A new management team led by Dr. Jacob Lalezari is in place, with an emphasis on scientific integrity and shareholder communication. Continued regulatory compliance and transparent reporting will be essential to regain and keep investor trust. Any lingering legal matters (such as the outcome of the DOJ case involving former executives) could have a reputational fallout but likely won’t directly impede operations if the company itself is not charged. Thus, cleaning up governance has been a necessary step and appears to be on track – this reduces one risk factor for the trajectory ahead.

Broader Breast Cancer Market Trends: The TNBC landscape is part of the larger breast cancer treatment trend moving toward personalized and combination therapies. A factor that could influence leronlimab’s adoption is how the treatment paradigm evolves. For example, increasing use of neoadjuvant therapies (treatments before surgery) in earlier-stage TNBC might change the nature of metastatic disease (patients relapsing later might have more resistant disease). Also, the distinction between TNBC and other subtypes could blur if new classifications (like tumor gene expression profiles) lead to different segmentations. CytoDyn will benefit if the paradigm increasingly recognizes the role of the tumor microenvironment and metastasis pathways – which would highlight CCR5’s relevance. Publications and academic interest in CCR5 and cancer could thus indirectly boost CytoDyn’s prospects. The company is contributing by preparing publications on its TNBC results for peer-reviewed journals, which will engage the oncology community and could spur investigator-initiated studies (like the mentioned Alzheimer’s and HIV-cure pilot studies leveraging leronlimab’s unique mechanism). These kinds of scientific developments can create a favorable environment for acceptance of a new therapy if it gets approved.

In summary, CytoDyn’s path forward will be shaped by a confluence of regulatory milestones, trial outcomes, and external market conditions. The company appears to have navigated out of a period of regulatory and legal uncertainty (FDA hold lifted, lawsuits settled), setting the stage for focusing on execution. Key positive inflection points would include securing breakthrough status, initiating/completing pivotal trials, and possibly aligning with a strategic partner – any of which would likely be met with strong market enthusiasm. Conversely, macro challenges like funding the environment or competitor successes could pressure CytoDyn to deliver exceptional results to stay competitive. Stakeholders should keep a close watch on FDA communications, trial progress updates, and industry deal-making as barometers of CytoDyn’s trajectory through 2025 and into 2026.



Projects and Expenditures in North America and Europe

CytoDyn’s operations span primarily North America, with growing engagement in Europe for scientific and future commercial efforts. The company’s projects (clinical trials, partnerships, manufacturing) and financial allocations reflect a strategy to advance leronlimab on both continents, albeit with different focuses. Below is a breakdown of key projects and expenditures by region, along with their strategic priorities and expected impact on growth:

North America (United States & Canada):

This is CytoDyn’s core domain for R&D and clinical development. Most of the company’s expenditures are directed here, as the U.S. is where virtually all its trials are being conducted and where the company is headquartered (Vancouver, Washington). Key North American projects include:

• Clinical Trials in the U.S.: CytoDyn’s active and planned trials are largely U.S.-based. For instance:

• The Phase II trial in metastatic colorectal cancer (CRC) (for MSS CRC patients) was cleared by the FDA in late 2024 and will be conducted at U.S. sites (with Dr. Ben Weinberg at Georgetown as lead investigator). CytoDyn has hired Syneos Health (a global CRO) to run this study. Expenditures for this trial include CRO fees, clinical site costs, and drug supply – these are budgeted as part of 2025 R&D spend. Success in this trial could open another oncology indication for leronlimab, providing growth beyond breast cancer.

• The planned Phase II inflammation trial (possibly in NASH or Long COVID or another inflammatory condition) is also set in the U.S., aiming to elucidate leronlimab’s mechanism in immune modulation. While a secondary priority to oncology, this could broaden CytoDyn’s pipeline if funded (perhaps through partnerships given limited internal budget).

• Follow-up TNBC trials: As discussed, a new TNBC trial (Phase II/III) will likely be U.S.-led. CytoDyn will leverage its previous trial site network (which included institutions like Northwestern, Vanderbilt, MD Anderson, etc., per earlier announcements) for any future study. The company has also re-engaged Dr. Richard Pestell, a leading oncologist, as a consultant for oncology programs including TNBC, indicating commitment to push this forward domestically. The cost of a Phase IIb or III TNBC trial in North America will be a major expenditure – potentially requiring tens of millions of dollars – which the company might seek a partner or special funding for if it goes alone.

• HIV trials in North America: With the FDA hold lifted, CytoDyn may conduct a smaller HIV trial in the U.S. to support a BLA resubmission (possibly focusing on HIV patients with persistent inflammation or as an adjunct in stem cell transplant for cure research). The cost here could be partly defrayed if it’s an investigator-initiated study (as hinted for the HIV cure project). The company also previously ran pivotal HIV trials in the U.S. (completed by 2019) and might not need a large new trial if prior data is sufficient after addressing FDA questions. However, some expenditures continue for regulatory compliance and maintaining BLA readiness.

• Manufacturing and CMC (Chemistry, Manufacturing, and Controls): CytoDyn’s manufacturing efforts are mostly based in North America (with some international partnerships). The drug substance for leronlimab has been produced by Samsung BioLogics (South Korea) under a long-term agreement, but drug product (fill-finish) and additional production is involved in the U.S. For example, Ajinomoto Bio-Pharma Services (with facilities in California and Belgium) has been partnering with CytoDyn to provide fill-finish manufacturing for leronlimab. This partnership was initially to support COVID-19 trial supply in 2020, but Aji Bio-Pharma also has capacity for other indications. CytoDyn’s CMC spending ($3.87M in FY2024) indicates ongoing production of leronlimab for trials. The North American expenditure includes maintaining inventory of clinical grade leronlimab, tech transfer processes, and quality testing. Having drug supply ready is crucial for any quick trial expansion or eventual commercial launch. The impact on growth is indirect but vital: reliable manufacturing enables the company to scale up trials or meet potential demand if approval comes. CytoDyn’s contract with Samsung (2019–2027) was structured to support up to multiple indications and large-scale production, which positions them to deliver drug product in North America and beyond when needed. Essentially, North America (and partnerships with companies that have U.S. presence) is where leronlimab’s manufacturing pipeline is being built, an investment that underpins future revenue capabilities.

• R&D Collaborations and Academic Partnerships: CytoDyn has engaged North American research institutions in its programs. For example, it announced a research partnership with Albert Einstein College of Medicine/Montefiore in New York for an HIV-related study. It’s also working with consultants in the U.S. (the new team of Dr. Palmer for NASH, Dr. Pestell for oncology, etc.). These collaborations often involve sponsored research funding or providing drug for pilot studies – modest expenditures that could yield data supporting new indications. The Alzheimer’s disease pilot mentioned (likely U.S.-based investigator-initiated) would be an example where CytoDyn provides leronlimab and maybe a small grant, but the bulk of the study is externally funded. This approach is cost-effective to explore new uses without diverting too much capital.

• Corporate and Administrative Base: The company’s HQ in Washington state and operations in California (the CEO and some teams are based in the Bay Area) mean general administrative costs are mostly North American. CytoDyn has streamlined these costs recently (headcount reduction in 2022–2023 in the U.S.) to conserve cash. While G&A doesn’t drive growth directly, prudent management of these expenses in North America ensures more funds are directed to productive R&D. The CEO’s letters emphasize careful, “one step at a time” progress and aligning resources with priorities – reflecting a strategy to keep administrative burn low while focusing spending on clinical projects.



Europe:

While CytoDyn does not yet have clinical trials running in Europe, it has begun to lay groundwork on the continent in several ways. The expenditures in Europe are currently smaller relative to North America but are poised to increase as the company moves toward regulatory engagement and potential market entry into the EU/UK. Key European-related activities include:

• Scientific Presence and Conferences: CytoDyn is actively seeking to present data in European forums. The submission of the TNBC survival data to the ESMO Breast Cancer 2025 conference (to be held in Europe) is a strategic move to gain visibility among European oncologists. While not a direct expenditure in the sense of a trial, the company will allocate budget for conference participation, publication fees, and possibly European Key Opinion Leader (KOL) outreach. The expected impact is to build credibility and interest in leronlimab among the European medical community, which could be valuable for future trial collaborations or compassionate use requests. A strong reception in Europe might also attract potential European partners or investors who see the promise in leronlimab’s data.

• Regulatory Consulting and Applications: As CytoDyn inches closer to possible approval filings, it will likely invest in European regulatory consulting. This could involve hiring advisors to navigate EMA processes or file for designations like EMA’s PRIME (Priority Medicines) or Orphan status. While there’s no public confirmation yet, it would be a logical step to apply for EMA PRIME designation for mTNBC if Phase II data are compelling, since PRIME can offer support like FDA Fast Track. The cost of such regulatory activities is not large (mostly professional fees) but strategically important. If CytoDyn can obtain EMA’s attention or support, it sets the stage for broader approvals. For example, Immunomedics was on track to file Trodelvy in Europe by 2021; CytoDyn could similarly plan a marketing authorization application (MAA) in Europe once it has phase 3 data. Aligning the U.S. and European development can maximize the global impact of leronlimab.

• Manufacturing and Supply Chain in Europe: CytoDyn’s manufacturing partners give it a foothold in Europe. Notably, Ajinomoto Bio-Pharma Services has a manufacturing site in Belgium, which could be utilized for supplying European trials or early launch material. By partnering with a CMO that has EU facilities, CytoDyn ensures its drug product can be made to EU standards and shipped within Europe efficiently. Additionally, Samsung BioLogics in South Korea can supply globally; any product destined for Europe would need to meet EMA release criteria, which would be part of CMC regulatory submissions. These partnerships mean that some manufacturing expenditure effectively occurs in or for Europe (e.g., fill-finish in Belgium). As trials expand, CytoDyn might initiate a European clinical site or expanded access program – having EU-released drug supply ready will facilitate that. The impact here is enabling future European trials without delay and showing potential partners that manufacturing is in place.

• Future European Trials or Expanded Access: While none are active yet, by 2025–2026 CytoDyn might consider opening trial sites in Europe for a Phase 3 program. This would be a new expenditure line – contracting European hospitals and investigators. It could be justified to speed enrollment and to satisfy regulators that the data apply to European populations. Moreover, CytoDyn could pursue an Expanded Access or Compassionate Use program in Europe for mTNBC if there is demand after ESMO presentation. For example, if European oncologists see the 36-month survivor data and have patients with no options, they might request the drug under compassionate use. CytoDyn would then supply drug (likely free of charge initially) – which is an expense – but it builds real-world experience and goodwill. Such programs can sometimes lead to early adoption and support when the drug is approved. The company hasn’t announced this, but it’s a potential strategic move once more data is public.

• European Partnerships and Licensing: CytoDyn’s mention of seeking partnerships includes global contexts. A partnership with a European pharma for either HIV or cancer could involve that partner funding or running European trials. For instance, if a European oncology company is interested in leronlimab for metastasis, they might license European rights and take on development locally. The financial allocation in that case might even be borne by the partner, reducing CytoDyn’s expenses but accelerating progress. While speculative, the company has explicitly said it sees “significant partnership and/or drug approval” potential in oncology. Europe is a likely area for such a partnership because CytoDyn currently lacks on-the-ground infrastructure there. Any deal with a European partner could bring upfront cash (improving CytoDyn’s finances) and commit that partner to spend on European regulatory filings and marketing – thus indirectly contributing to CytoDyn’s global growth without CytoDyn spending those resources itself. The expected impact of such a strategic move would be a faster and broader market penetration for leronlimab, plus validation by a larger entity.



Allocation and Impact Summary:

• In financial terms, the bulk of CytoDyn’s spending remains in North America – for FY2024, essentially all $7.2M R&D was for U.S.-based projects. European-focused spending has so far been limited to manufacturing arrangements and conference/regulatory prep, which are a small fraction of the budget. However, as programs mature, one should expect an uptick in EU-related expenses (regulatory filings, possible local trials). The company will carefully allocate funds to Europe when there is a clear return (e.g., preparing for an MAA submission would be worth the cost once Phase 3 data is at hand).

• In terms of strategic priorities, North America is about execution and data generation (getting trials done, getting FDA approval), while Europe is about expansion and future market access. CytoDyn’s near-term priority is to achieve success in the U.S. first – as evidenced by prioritizing the FDA clearance and U.S. trial starts. Europe strategy is somewhat contingent on U.S. results, but the company is already signaling its intent not to ignore Europe (by engaging via ESMO, etc.). This two-pronged approach ensures that CytoDyn positions leronlimab as a global product in the long run.

• The expected impact on growth from North American projects is straightforward: successful U.S. trials and FDA approvals would allow product launch in the U.S., driving revenue growth starting (optimistically) in late 2026 or 2027. The U.S. market alone for TNBC and HIV could be significant (tens of thousands of patients). Meanwhile, the groundwork in Europe means that once the U.S. validation is achieved, CytoDyn can rapidly follow in Europe, potentially doubling the accessible market. If a partnership is secured in Europe, growth could also come in the form of milestone payments which would bolster CytoDyn’s finances even before sales. In essence, North America is the springboard for CytoDyn’s growth, and Europe is the amplifier that can later broaden that growth and add longevity (through additional exclusivity and markets).



Conclusion

CytoDyn (CYDY) is at a critical juncture, advancing its flagship molecule leronlimab through both challenges and opportunities. In metastatic triple-negative breast cancer, leronlimab has shown encouraging signs of efficacy (improved survival and disease control) that have earned it FDA Fast Track designation and positioned it for potential Breakthrough designation. The company’s diligent focus on this indication – including new combination studies and planned trial expansions – reflects a strategic shift to prioritize oncology as the key value driver. At the same time, CytoDyn continues to pursue its roots in HIV therapy and explore immunology applications, leveraging the broad mechanism of CCR5 blockade.

From an investment perspective, CytoDyn presents a high-risk, high-reward profile for late 2025 through mid 2026. Historically volatile, the stock has been influenced by clinical news and external events – skyrocketing during the COVID-19 hype only to crash and rebuild investor trust. Going into 2025, with cleaned-up management and clearer data, the stock is modestly rebounding around the higher $0.30–$0.40 range. Key financial indicators suggest a company still in the development stage: no revenue yet, ongoing losses, but tightly managed expenses and a recent influx of cash from legal wins and financing. R&D spending is ramping up again ($7.2M in FY2024 vs $2.6M in FY2023), which is a positive indicator that pipeline activity is restarting, though it also means the cash burn will increase. The outlook for Q4 2025 – Q2 2026 will depend heavily on execution of trials and securing of partnerships – successes there could materially improve CytoDyn’s financial position and stock performance, whereas any setbacks would raise concerns given the limited cash on hand.

In the competitive arena, CytoDyn faces formidable players in the mTNBC space, from giants like Gilead and Merck to emerging ADCs. Trodelvy (Gilead) sets a high benchmark in third-line TNBC (with ~12-month OS). However, leronlimab’s early results appear to at least match this benchmark, and its novel approach offers a complementary angle (metastasis inhibition) rather than directly colliding with cytotoxic agents. If properly developed, leronlimab could find a niche as an add-on therapy to enhance current regimens – a position that might invite collaboration rather than pure competition. CytoDyn’s challenge will be to demonstrate clear additive benefit and carve out a role in treatment protocols that are becoming increasingly crowded. The company’s smaller size is counterbalanced by the focus and flexibility it has in pursuing innovative combination trials (e.g., with Keytruda or Trodelvy) that larger companies might not initiate on their own.



Regulatory and market factors present both hurdles and tailwinds. The lifting of the FDA hold in 2024 has removed a major obstacle and restores CytoDyn’s credibility with regulators. Upcoming FDA interactions (for BTD, trial designs, etc.) will be crucial – a cooperative FDA could accelerate timelines, whereas additional requests or caution could prolong development. The biotech funding environment and potential for partnerships will influence how fast CytoDyn can move without running low on resources. Encouragingly, interest from third parties has grown and the company expects to finalize some research partnerships that could offload costs. Broader trends like big pharma’s appetite for oncology acquisitions (as seen with Immunomedics and Seagen deals) could eventually benefit CytoDyn if leronlimab continues to prove its worth.

Geographically, CytoDyn is aligning its North American efforts to generate pivotal data and is beginning to engage Europe to widen its reach. The financial allocations clearly favor North America at present – that’s where trials are happening, and money is spent – but Europe stands as a significant future market. Through partnerships with contract manufacturers (like Ajinomoto in Belgium) and scientific presentations (ESMO), CytoDyn is laying the groundwork in Europe that could be leveraged once U.S. success is achieved. This global outlook is important for a small biotech; it maximizes the eventual commercial potential of leronlimab and could make CytoDyn an attractive partner or acquisition target.

In conclusion, CytoDyn’s trajectory from late 2025 into 2026 will be defined by execution on multiple fronts – clinical, regulatory, financial, and strategic. The company’s leadership expresses confidence that 2025 will mark a true turnaround, with an emphasis on “making 2025 a pivotal year” and delivering data that “unequivocally demonstrate” leronlimab’s impact. For investors, CytoDyn represents a speculative bet on a once-celebrated drug that is now steadily rebuilding its case. If leronlimab can fulfill its early promise in metastatic triple-negative breast cancer, the rewards could be substantial: FDA approvals, partnerships, and entry into a multi-billion-dollar oncology market. However, the risks – scientific, financial, and competitive – remain considerable until more definitive results are obtained. Stakeholders should thus expect continued high volatility but also potentially transformational milestones in the coming 18–24 months. CytoDyn’s story will be one to watch, as it attempts to convert scientific innovation into clinical success and shareholder value, both in North America and abroad.

TM Editors' note: This article discusses a penny stock and/or microcap. Such stocks are easily manipulated; do your own careful due diligence.

Tiny-Ad-8280

“It’s Just a Poster…” Until It Saves Lives. 40 Days...
Let’s not sugarcoat it.

“It’s just a poster.” “We’ve been here before.” “If this were real, we’d already know.”

That’s what they’re saying.
Some with cynicism.
Some with scars.
And honestly? I get it.

But if you’ve ever paid attention to oncology, you know:

The biggest revolutions start small.

And this one — if it holds — could be one of the biggest of all.

🧬 Let’s rewind to 2015
Immunomedics walked into ASCO with Trodelvy, a drug nobody cared about yet.

58 women with stage 4 triple-negative breast cancer

17 had some tumor shrinkage

2 had full tumor disappearance

No survival data

No media frenzy

Just a quiet little poster tacked to a wall

No one said,

“This changes everything.”

But five years later?
Trodelvy becomes the largest breast cancer acquisition in history.
$21 billion.
Because that poster was the spark.

It didn’t show a cure.
It showed a signal.

🧬 Now it’s 2025. And Leronlimab is bringing more than a signal.
It’s not just a tumor response.
It’s not a 3-month bump in survival.

It’s stage 4 breast cancer patients — alive and well, three years later.
It’s people who failed every line of chemo — now cancer-free.
It’s data that, if true, doesn’t just whisper “potential.”

It screams: hope is back.

Let me make this brutally clear:

✅ This is metastatic triple-negative breast cancer
✅ The kind that kills in 6–12 months, even with treatment
✅ These women were told, “There’s nothing more we can do.”
✅ And now some are alive 36+ months later, with no cancer left to find

You don’t see that.
Not in this disease.
Not at this stage.
Not ever.

📊 Let’s stack it side by side — facts only:
🧬 Trodelvy (2015) vs Leronlimab (2025)
Poster vs Poster. Hope vs Survival.

Metric Trodelvy (2015 Poster at ASCO) Leronlimab (2025 Poster at ESMO)
Trial Phase Phase 1/2 Phase 1b/2 (Basket Trial)
Patients 58 with mTNBC (chemo-refractory) 30 with mTNBC (chemo-refractory)
Tumor Shrinkage 17 of 58 (~31% response rate) Some complete responses (NED); numbers coming at ESMO
Complete Remissions 2 confirmed Confirmed NED cases; final count revealed at ESMO
Median Survival Not reported >50% alive at 12 months
Long-Term Survivors None reported 36+ monthsSome alive , cancer-free
Grade 3/4 Side Effects 39% neutropenia, 13% diarrhea (chemo-like toxicity) Zero Grade 3/4 treatment-related adverse events
Now let me decode that last line for everyone without a medical degree:

🩸 Trodelvy’s early success came with real toxicity.

4 in 10 patients developed neutropenia — dangerously low white blood cells that can lead to life-threatening infections.

Over 1 in 10 had severe diarrhea — the kind that can land you in the hospital.

These are Grade 3 or 4 side effects, the most serious in cancer trials. They’re manageable — but not easy. This is classic, brutal chemo.

🌱 Leronlimab’s early trial?
Zero of those severe, drug-related side effects reported.
Not one patient experienced life-altering toxicity due to the drug.
No fevers. No bone marrow suppression. No emergency transfusions.
Just a targeted immune modulator that — somehow — gave patients time, without taking their quality of life.

You know what that means?
These women weren’t just alive longer.

They were living longer — without suffering.

That is not normal. That is not expected. That is not pharma-as-usual.

That is a breakthrough.

“But it’s just a poster…”
Yes.
So was Trodelvy.

So were the first data points from Keytruda, from Opdivo, from every life-saving drug in oncology history.

Because posters are where revolutions begin.

And this one?
Might be the most important ever tacked to a conference wall.

TL;DR:
“We’ve seen this before.”

No. You haven’t.

You’ve seen companies chase survival.
Now you’re seeing it.

You’ve seen drugs buy patients time.
Now you’re seeing people beat the clock.

And in 40 days, on a poster board in Munich,
you’ll see the data that proves it.

So roll your eyes.
Call it hype.
Say “we’ve heard this before.”

But when those survival curves drop…
when you see “36+ months” in a disease that gives you 6…

You’ll remember this post.

And you’ll realize:

This wasn’t another story.
This was the beginning of the ending — of metastatic breast cancer.

— Tiny 🧬

Website corrected regarding CRC:

https://www.cytodyn.com/pipeline

Tiny-Ad-8280

🧬 A Tiny Dose of CYDY — 41 Days to ESMO
“Phase 3? Wait… what?”

You’re not crazy. CytoDyn just updated their website to show the CRC (colorectal cancer) trial as Phase 3 — even though ClinicalTrials.gov still says Phase 2.

So what gives?

Let’s break it down for everyone wondering the same thing 👇

🧪 First: Can you skip from Phase 2 to Phase 3?
Yes — but not without serious work behind the scenes.

To call something a Phase 3 trial, CytoDyn would’ve had to:

Amend the protocol (trial plan) to reflect Phase 3 endpoints — meaning stricter goals, more patients, usually randomized.

Submit that new plan to the FDA under their IND (Investigational New Drug) application.

Wait for FDA sign-off — if the FDA doesn’t issue a “clinical hold,” the trial can proceed as Phase 3.

This isn’t a blog edit. It’s regulatory law.

🧠 Why would the website show Phase 3 if ClinicalTrials.gov doesn’t?
A few totally legit reasons:

ClinicalTrials.gov updates slowly. It often takes weeks after a trial is amended or begins dosing before the public registry is updated.

They’re waiting for “First Patient In” (FPI) — which is when most companies announce a trial has officially begun.

They may be saving the announcement for ESMO — when everyone’s watching.

This kind of update doesn’t happen by accident. You don’t “misclick” a Phase 3.

📰 But shouldn’t they PR it?
Short answer: they will.

Companies typically issue press releases when:

The first patient is treated in the new trial.

They want to make a big splash — like pairing the CRC Phase 3 with mTNBC survival data at ESMO.

Or when it’s strategically beneficial (e.g. upcoming financing, partnership talks, etc.).

Until then? They’re allowed to update internal and investor materials — especially if they’re accurate.

🎯 So is this real?
🧠 Logically? Yes.

They wouldn’t update a website during a critical moment — with all eyes on them — unless this was intentional and grounded in upcoming action.

And the fact that this trial is being run with Syneos and Georgetown’s Dr. Ben Weinberg as PI (Principal Investigator)? That’s serious firepower. You don’t upgrade to Phase 3 unless the foundation is there.

📈 So what does this mean for the stock?
Let’s be real here:

41 days to ESMO with mTNBC survival data showing 36+ months NED in stage 4 cancer

A website quietly updated to show a Phase 3 CRC trial

Short interest rising (now at 28 million shares)

And a share price still in the 20-cent range

That’s a setup. A real one.

If ESMO hits like we think it will — and the CRC trial is truly Phase 3 — the price action won’t be subtle.

This is the calm before the chart.

TL;DR:
This Phase 3 listing is probably legit.
The market hasn’t noticed.
But the ones shorting this?
They’re about to.

41 days.
And counting.

— Tiny 🧬

Designer_Anteater_18

Reasons to go from Phase 2 to Phase 3 colorectal trial before enrollment
How did cytodyn move its colorectal trial from a phase 2 trial to a phase 3 trial? What could have happened to have this change before enrollment?

ChatGPT said:
If CytoDyn has moved its relapsed/refractory microsatellite-stable colorectal cancer (CRC) trial from Phase 2 to Phase 3 before enrollment, several key factors could have influenced this shift:

Possible Reasons for the Change:
Strong Preliminary Data

If CytoDyn or its research partners (Syneos Health, academic institutions, or other collaborators) provided compelling preclinical or early clinical data (such as compassionate use or investigator-led studies), the FDA might have been convinced that a Phase 3 trial was justified.

Fast Track or Breakthrough Designation

If the FDA granted Fast Track, Breakthrough Therapy, or Accelerated Approval pathways, they may have allowed the trial to jump directly to Phase 3 to expedite approval.

Agreement with the FDA (End-of-Phase 2 Meeting)

CytoDyn may have had discussions with the FDA in an End-of-Phase 2 meeting, where they provided data that satisfied Phase 2 requirements and allowed for a direct transition to Phase 3.

Regulatory Strategy Change

CytoDyn might have restructured its clinical trial design (e.g., increasing sample size, modifying endpoints) to meet Phase 3 standards upfront, possibly in alignment with a potential partner’s requirements.

A Confirmatory Trial Approach

If the FDA agreed that Phase 2 endpoints were sufficient for efficacy, CytoDyn could have adjusted the trial into a pivotal Phase 3 study serving as a confirmatory trial for approval.

Potential Partnership Influence

A pharmaceutical partner (GSK, Merck, or another company) might have pushed for a direct Phase 3 trial as part of a licensing deal.

Updated Scientific Findings (CCR5 Mechanism in Oncology)

New discoveries or peer-reviewed studies supporting CCR5 inhibition in colorectal cancer might have strengthened the case for a direct Phase 3 move.

What Would This Mean for CytoDyn?
Saves time: Skipping Phase 2 saves 1-2 years in the regulatory process.

Higher valuation: A Phase 3 asset attracts more partnerships, institutional investors, and buyout interest.

Increased funding opportunities: Moving to Phase 3 suggests FDA confidence, which can help raise money from investors or government grants.

This move could be huge for CytoDyn, especially if it means leronlimab’s oncology applications are proving to be strong enough to go straight to a pivotal trial.

Website new look/rebranding underway:

https://www.cytodyn.com/


CRC listed as Phase 3????

Trying to dumb it down. It is what basher's understand.

I like strawberry preserves on my whole wheat peanut butter sandwich. Combo' s work better together. Still waiting to find out if leronlimab is the peanut butter, jam or the bread that holds it together.

Tiny-Ad-8280

🧬 A Tiny Dose of CYDY — Countdown to ESMO - A New Series - 🗓 49 Days Until May 15th
🚨 Title: Stage 4. Terminal. Now Cancer-Free?! At 25¢?!

Let’s set the stage…

Stage 4 metastatic triple-negative breast cancer (mTNBC) is a death sentence.
It spreads fast. It ignores most treatments.
Once it hits your brain, lungs, or liver… you’re done.

📉 Median survival? Around 12 months.
📈 Long-term survival? Almost nonexistent.
🎯 Cure? Not a thing.

So what if I told you a company trading for 25¢ just treated 30 of these terminal patients…
…and now says a subgroup is 36+ months out, alive and cancer-free?

You read that right.
No cancer. No progression. No recurrence.

🧪 The drug? Leronlimab.
👨‍⚕️ The company? CytoDyn ($CYDY).
📍 The event? ESMO Breast Cancer Conference — May 15th.

This isn’t hype. It’s from their February press release:

“A small group of patients who failed treatment after developing metastatic disease survived more than 36 months after receiving leronlimab… and currently identify as having no evidence of ongoing disease.”

That’s unheard of.
That’s not how stage 4 works.
That’s not supposed to happen — but it did.

And the world finds out what really happened 49 days from now.

👀 Until then…
Sit tight. Do your homework.

And check back tomorrow for your next Tiny Dose of CYDY.

https://www.targetedonc.com/view/leronlimab-gets-fda-nod-for-phase-2-microsatellite-stable-crc-trial

Leronlimab Gets FDA Nod for Phase 2 Microsatellite-Stable CRC Trial
March 27, 2025
By Jordyn Sava
Fact checked by Jason M. Broderick
News
Article







A phase 2 trial will evaluate leronlimab’s safety and efficacy for the treatment of patients with microsatellite stable metastatic colorectal cancer.


US FDA
US FDA


The FDA has granted clearance for the start of a phase 2 study (NCT06699835) evaluating leronlimab in patients with relapsed/refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

Leronlimab works by targeting CCR5 markers on the tumor.

The open-label, randomized, 2-arm, multicenter trial will evaluate leronlimab’s effect on the overall response rate (ORR), overall survival (OS), safety, and tolerability when combined with trifluridine and tipiracil (TAS-102; Lonsurf) and bevacizumab (Avastin) in patients with CCR5-positive (CCR5+), MSS, relapsed/refractory, mCRC.


The FDA has cleared the initiation of a phase 2 study assessing leronlimab for the potential treatment of patients with MSS relapsed/refractory mCRC.1

The phase 2, open-label, randomized, 2-arm, multicenter study will include patients with CCR5+ MSS mCRC. Patients will receive either leronlimab at a dose of 350 mg in combination with TAS-102 and bevacizumab or a 700 mg dose of leronlimab in combination with TAS-102 and bevacizumab to assess the agent’s effect on ORR, OS, safety and tolerability.2

Enrollment is open to patients aged 18 years and older with a history of treated colorectal cancer with unresectable metastases of the primary colorectal cancer to other organs. If patients are HIV-1 positive, their viral load must be below 50 copies/ml and the patient must be on stable ART for at least 3 months. Patients are required to demonstrate positive tumor expression of CCR5 by immunohistochemistry (IHC), have an expected survival of at least 3 months, have measurable disease per RECIST 1.1, have an ECOG performance status of 0 or 1, and have adequate organ and bone marrow function within 28 days prior to registration.

Adult patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. Further, patients must be histologically confirmed for MSS colorectal cancer by IHC or next-generation sequencing. Patients must not have received anticancer treatment within the last 4 weeks or at least 5 half-lives prior to treatment.


3D medical illustration of colorectal cancer: © anatomy insider - stock.adobe.com
3D medical illustration of colorectal cancer: © anatomy insider - stock.adobe.com


The primary end point is ORR and secondary end points include treatment-emergent adverse events, defined as events with an onset on or after the first treatment, and duration of response.

This study plans to enroll approximately 60 patients, 30 in each of 2 arms, and has an estimated primary completion date of June 2028.


About Leronlimab
Leronlimab targets CCR5 markers on the tumor.3 Prior findings have already shown leronlimab’s potential in oncology, particularly in metastatic triple-negative breast cancer (mTNBC). According to a pooled analysis of 3 clinical trials presented at the 2022 American Society of Clinical Oncology Annual Meeting looking at 28 patients with mTNBC treated with leronlimab at doses of 350 mg, 525 mg, or 700 mg, the median progression-free survival (PFS) observed was 3.8 months. An OS of 6.6 months was also shown.


In the subset of patients who were given higher doses of leronlimab (525 mg or 700 mg), the median PFS extended to 6.1 months, with OS exceeding 12 months.


Leronlimab was generally well tolerated, with a few grade 3 treatment-emergent adverse events.

Creatv will perform the LifeTracDx****® liquid biopsy in a number of CytoDyn studies including NCT06699835.

BuildGoodThings

LifeTracDx® liquid biopsy in a number of CytoDyn studies
Bio4 at stocktwits posted this little gem today. Thank you!

https://stocktwits.com/Bio4/message/609426008
original source link is https://www.prnewswire.com/news-releases/lifetracdx-blood-test-to-be-performed-in-key-colorectal-clinical-trial-302412481.html

MONMOUTH JUNCTION, N.J., March 27, 2025 /PRNewswire/ -- Creatv Bio, a Division of Creatv MicroTech, Inc. (Creatv) will be collaborating with CytoDyn Therapeutics Corporation (CytoDyn) to assess patient response to their drug using the LifeTracDx® blood test.

CytoDyn has received FDA clearance to initiate a Phase II study of leronlimab in patients with relapsed or refractory micro-satellite stable colorectal cancer (CRC) (NCT06699835). The drug, leronlimab, targets CCR5 marker on the tumor.

Creatv will perform the LifeTracDx****® liquid biopsy in a number of CytoDyn studies including NCT06699835. The LifeTracDx® test is based on analyzing two biomarkers: (1) circulating tumor cells (CTCs) and (2) Cancer Associated Macrophage-Like (CAML) cells, which are macrophages that engulf tumor cells. Both CTCs and CAMLs contain tumor material.

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.

Tiny-Ad-8280

🚨 “How the Hell Is Leronlimab Doing This?” — MGK's Latest Post, Simplified 🚨
Let’s break down what the science nerd (MGK_2) just said in a way that actually makes sense.

What we’re talking about is metastatic triple-negative breast cancer (mTNBC) — aka the most aggressive, hardest-to-treat form of breast cancer, and stage 4, meaning the cancer has spread to other organs like the brain, lungs, or liver.

🧬 Most Cancer Drugs Just Slow It Down.
Leronlimab might actually be shutting it down. Here’s how:

🧠 What Is Leronlimab Even Doing?
Cancer spreads by breaking out of the original tumor and invading the rest of the body — it’s like a fire jumping houses. The tools it uses to do this are special chemical pathways. One of them involves a receptor called CCR5.

Leronlimab is an antibody that blocks CCR5.

That’s like boarding up the fire exits, stopping the cancer from escaping and spreading.

🧪 What Did MGK’s Post Say (But 50x Simpler)?
Here’s the TL;DR of what he posted, without the 10,000-word medical jargon:

✅ Leronlimab blocks the pathway (CCR5) that cancer cells use to:
Spread through the bloodstream or lymph system

Invade other organs

Avoid detection from the immune system

Repair themselves after chemo or radiation

Live forever (immortal cancer cells)

🧨 So when Leronlimab hits them, a few things happen:
They stop moving (less metastasis)

They become easier to kill with chemo

They don’t grow back as easily

The immune system has a better shot at recognizing and destroying them

🧪 Mouse Data Was Insane (Yes, Mice — but Still Important)
Leronlimab was tested in mice with human breast cancer cells injected into them (they use special immune-deficient mice so the human cancer doesn’t get rejected).

What happened?

Leronlimab cut the spread of breast cancer by 98–99.6%.
That’s basically “the cancer tried to spread… and failed.”

In plain speak: it not only stopped the fire — it flooded the house.

🔬 And What About in Humans?
Now that we’ve seen the animal data, let’s connect it to what we know from CytoDyn’s human trials:

30 patients with stage 4 mTNBC

Most had failed other treatments

Many had cancer in their brain, liver, and lungs

Small group now alive 36+ months later and cancer-free

MGK’s post helps explain how this may be happening — by cutting off the cancer’s ability to metastasize and survive.

🧠 Coolest Analogy MGK Used (And He Didn’t Even Know It)
"Think of your body like a car.
If the gas pedal (cancer growth) is stuck AND the brakes (tumor suppressors) are broken… the car speeds up until it crashes (cancer).
Leronlimab may be helping slam the brakes."

That’s what we’re looking at here — not just a drug that slows cancer, but one that may be restoring balance to the system.

💥 TL;DR for Non-Doctors
Cancer spreads using CCR5. Leronlimab blocks it.

Stops invasion. Makes chemo work better.

Massive impact on metastasis.

In mice, cut lung tumors by 98%.

In humans? Early signs say it may be doing the impossible.

MGK’s post was dense, but the message is this: Leronlimab isn’t just another drug — it’s a whole new way to fight cancer.

And guess what?

We get to see real long-term survival data — in actual humans — on May 15 at ESMO.

So yeah… 25¢ today might be the deal of the decade.

Let the countdown begin. 🔥

MGK_2

Neoplasm & Immunity
Neoplasm is an abnormal mass; an uncontrolled and uncoordinated persistent growth of tissue, even when the stimulation for growth is gone. The growth or proliferation of the tumor is uncontrolled.

Neoplastic malignant cells are not well differentiated. The tumor cell is usually only modestly comparable to a normal cell. Anaplastic tumors have no differentiation and have tremendous variation between individual cells of the tumor.

A cancerous and / or malignant tumor ends in -sarcoma or -carcinoma. Examples include: Fibrosarcoma. Chondrosarcoma. Adenocarcinoma. Squamous Cell Carcinoma, Renal Cell Carcinoma.

mTNBC (metastatic Triple-Negative Breast Cancer) is a carcinoma, not a sarcoma.

Its official name is metastatic Triple-Negative Breast Cancer (mTNBC). It is a subtype of invasive ductal carcinoma (IDC) which lacks estrogen receptors (ER), progesterone receptors (PR), and HER2 expression. Because of this, it does not respond to hormonal or HER2-targeted therapies, making treatment more challenging.

The key difference between carcinoma and sarcoma lies in the type of tissue from which they originate:

Carcinoma – A cancer that arises from epithelial cells, which line the surfaces of organs, glands, and body cavities.

Common locations: Breast, lung, prostate, colon, pancreas, skin (e.g., basal cell carcinoma, squamous cell carcinoma).

More common than sarcomas.

Examples: Triple-Negative Breast Cancer (TNBC), lung adenocarcinoma, prostate carcinoma.

Sarcoma – A cancer that originates in mesenchymal cells, which form connective tissues such as bones, muscles, fat, cartilage, and blood vessels.

Less common but often more aggressive.

Examples: Osteosarcoma (bone cancer), Liposarcoma (fat tissue cancer), Rhabdomyosarcoma (muscle cancer).

So, mTNBC is a carcinoma because it originates from the epithelial cells in the breast ducts. Sarcomas, on the other hand, arise from the structural and connective tissues of the body.

Malignant tumors produce proteolytic enzymes that break down surrounding structures, such as vein and lymphatics, so as to invade those structures. Some structures try to resist metastatic invasion such as elastin, collagen, cartilage. Arteries are more resistant to metastatic invasion because of the elastin. But not veins. Not lymphatics and not peri-neuro spaces.

Metastasis is the spread from the tumor's primary site to somewhere else, distant and not continuous. Metastasis does not occur in benign tumors. Metastasis occurs through the body's passages. Respiratory tracts, Gastro-Intestinal Tract, Urinary Tract. A malignant tumor can use these natural passages to spread. A tumor of the lung can spread to another site in the lungs via the respiratory tract.

A malignant tumor can spread through natural body cavities. Pericardial cavity. The pleural cavity. The peritoneal cavity. There are spaces/cavities in the spinal cord. Subarachnoid space. The malignant tumor can detach from its primary site and enter these body cavities and spread. A tumor can go from the stomach to the ovary by entering the peritoneal cavity.

A tumor can use lymphatics to spread. Usually carcinomas spread via lymphatics. However, sarcomas can also spread via lymphatics. It is more common for carcinomas to use lymphatics to spread. Sarcoma usually spreads through the vein, not through the artery because of the high amount of elastic tissue in the artery.

The hallmark of a malignant tumor is anaplasia, invasion and metastasis. If the cells have not yet invaded the basement membrane, the tumor is not yet at least malignant. It may just be hypertrophied, swollen, indurated or enlarged. If the basement membrane of the organ tissue has been disrupted by the tumor, then it is Grade IV, malignancy because it has invaded another tissue.

The question then is how does leronlimab cure this? How does leronlimab prevent the cells of the body from becoming anaplastic? To becoming non-differentiated? To becoming immortal? To becoming unlimited in their replication? How does leronlimab make it no longer possible for the tumor to invade other tissues? How does it prevent future metastasis?

What lies at the heart of of Carcinogenesis? or What is the most important thing that is responsible for the development of cancer? A Non-Lethal Mutation lies at the heart of carcinogenesis. Inside the cell, you have a nucleus. Inside the nucleus, you have chromosomes. Inside every chromosome, you have the helical structured DNA. Inside these DNAs, we have genes. Genes are part of DNA. Genes are known as the unit of heredity. Genes are units of DNA that can encode a particular protein or an RNA molecule. That's about the extent of where I'll go with that definition of a Gene.

A mutation is a permanent hereditable change in the base sequence of the DNA of an organism. This mutation alters the Gene as well, because that mutation is also passed down to the daughter cell. So then a Non-Lethal Mutation does not cause the cell to die. If it were lethal, the cell would die and that would prevent any cancer from developing. If the cell dies, then there is no cancer. But if the mutation does not kill the cell, then that mutation could possibly lead to cancer, but for cancer to become more likely, the Proto-Oncogene and the Tumor Suppressor Gene should also be altered in that mutation to make cancer more probable.

If the Proto-Oncogene and the Tumor Suppressor Gene are mutated, then, there is a high possibility of cancer. The Proto-Oncogene encodes protein which regulates the rate of proliferation/growth and cell differentiation of the cell. The Proto-Oncogene is necessary for the normal growth and differentiation of our cells. When it mutates, it is called an Oncogene for a cancer Gene and that mutation can result in cancer development as a result of the mutated Proto-Oncogene.

Tumor Suppressor Genes are the opposite of Proto-Oncogenes. Tumor Suppressor Genes inhibit cell proliferation and tumor development. When this Gene mutates, the Tumor Suppressor Gene has diminished function and the tumor no longer is suppressed.

The best analogy is to use the analogy of a speeding car. If you're on the highway and you want to speed up, you press on the (Gas Pedal = Proto-Oncogene). If you want to slow down, you remove your foot from the Gas Pedal but unfortunately, the car doesn't slow down. Something is wrong. Your Gas Pedal is stuck. The Proto-Oncogene is like your stuck Gas Pedal. So, how do you slow the car down? You need to press on the (Brake = Tumor Suppressor Gene). Well, by doing so, the car hasn't slowed. The (Brakes are Defective because the Tumor Suppressor Gene has mutated), and you're driving fast. As we all know, the outcome is not good. (Crash = Cancer). If there is both a mutation to the Proto-Oncogene and also another mutation of the Tumor Suppressor Gene as well, then the car can't slow down and cancer is likely to form. Does leronlimab prevent these mutations from happening again in the future following a full blown treatment?

Other genes which could lead to cancer are genes that regulate apoptosis and genes that regulate DNA repair. If these genes mutate, then, cancer could form. Apoptosis is a pathway of programmed cell death, where the cells commit suicide. Apoptosis is a better alternative than continued living when the cell is so damaged that the DNA can no longer be repaired and when the risk of Gene mutation is great.

If the genes which regulate DNA repair are damaged, then that would result in decreased cellular DNA repair. So, now, in this scenario, the Proto-Oncogene and the Tumor Suppressor Genes get damaged, but they won't get repaired, and the result of that is a speeding car that can't stop = bad result = crash or the development of cancer in the long run. Tumor cells have impaired DNA repair capacity.

These malignant tumor cells also have unlimited replicative capability. This happens by maintenance of the length and function of the telomere. This makes these cells immortal.

Sustained angiogenesis, formation of new blood vessels. These cells need nutrients, blood supply. They induce angiogenesis via VEGF. Vascular Endothelial Growth Factor.

The cells have the ability to invade and metastasize.

So, let's take a look at how a Normal Cell transforms into a malignant tumor. It has to sustain some sort of DNA damage. Exposure to some DNA damaging agent causing Gene damage. That could be of chemical, viral or some radiation etiology. Exposure of these cells to such an insult could lead to such a mutation. Those insults could cause a mutation in the Gene DNA. If DNA Repair is intact, and if the damage is not that severe, then the cell possibly can restore itself back to normal. If DNA Repair is compromised, the cell possibly may not repair itself, or if the DNA simply is not repaired, then a mutation in the Genome of the cell may be incurred. This is a result of failure of Gene used for DNA repair. This could be a result in the Failure of the Gene that is used to Repair DNA or failure in the Gene used for Apoptosis. If the mutation which results causes a change to both the Tumor Suppressor Gene and to the Proto-Oncogene, that would lead to Unregulated Cell Proliferation. The mutation could also cause Apoptosis to turn off. In both of these scenarios, with Apoptosis turned off and with Unregulated Cell Proliferation, the Tumor grows and can't stop growing; expansion of the tumor cells. Eventually, the growing Tumor requires a collateral circulation for survival. This leads to Angiogenesis or the development of a collateral blood supply. The Tumor tries to evade the immune system. It develops a means by which to protect itself and to avoid immune detection, an escape from immunity. As the Tumor continues to grow, the malignant potential of the Tumor increases. Its aggressiveness increases. More mutations occur. Eventually, it breaks the basement membrane and eventually becomes malignant. Becoming malignant means invading another tissue. Metastasizing. The more mutations, the less likely to respond to therapy. The less antigenic the mutation is, the more likely it is to avoid immune detection and the more likely it is to survive. The more antigenic the mutation is, the less likely it is to avoid immune detection and the less likely it is to survive. Therefore, the mutations that avoid immune detection survive.

The question is how does formal treatment with leronlimab prevent any of that from happening again? How does it prevent it from happening for over 36 months when it was happening 3 years earlier to a great extent?

Let's keep all this in mind and let's go through this recently modified publication about CytoDyn's mTNBC trial performed over 3 years ago. The article was recently revised/modified on November 9, 2024: Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular metastasis and enhances cell death induced by DNA damaging chemotherapy.

"Background: Triple-negative breast cancer (BCa) (TNBC) is a deadly form of human BCa with limited treatment options and poor prognosis. In our prior analysis of over 2200 breast cancer samples, the G protein-coupled receptor CCR5 was expressed in >?95% of TNBC samples. A humanized monoclonal antibody to CCR5 (leronlimab), used in the treatment of HIV-infected patients, has shown minimal side effects in large patient populations.

Methods: A humanized monoclonal antibody to CCR5, leronlimab, was used for the first time in tissue culture and in mice to determine binding characteristics to human breast cancer cells, intracellular signaling, and impact on (i) metastasis prevention and (ii) impact on established metastasis.

Results: Herein, leronlimab was shown to bind CCR5 in multiple breast cancer cell lines. Binding of leronlimab to CCR5 reduced ligand-induced Ca+?2 signaling, invasion of TNBC into Matrigel, and transwell migration. Leronlimab enhanced the BCa cell killing of the BCa chemotherapy reagent, doxorubicin. In xenografts conducted with Nu/Nu mice, leronlimab reduced lung metastasis of the TNBC cell line, MB-MDA-231, by >?98% at 6?weeks*.* Treatment with leronlimab reduced the metastatic tumor burden of established TNBC lung metastasis.

Conclusions: The safety profile of leronlimab, together with strong preclinical evidence to both prevent and reduce established breast cancer metastasis herein, suggests studies of clinical efficacy may be warranted."
...

The above was revised November 9, 2024 and summarized the Research herein: Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular metastasis and enhances cell death induced by DNA damaging chemotherapy

*"*Leronlimab blocks CCR5-mediated invasion of human breast cancer cells into the extracellular matrix

The ability of breast cancer cells to invade extracellular matrix is distinguishable from but an important step in tumor metastasis*. To test the ability of leronlimab to block* cell invasion in 3D Matrigel invasion assay, MDA-MB-231 cells were used. CCL5 was used as a chemoattractant to induce invasion*. The small-molecule inhibitor of CCR5, vicriviroc, was used as a form of positive control. Leronlimab reduced CCL5-induced MDA-MB-231 breast cancer cell invasion with similar efficacy as vicriviroc (Fig.* 4a, b) (855?±?8.7, N?=?8 for control vs. 520?±?9.1?µM distance traveled, N?=?9 for leronlimab, P?<?0.001). We also tested the effects of different doses of leronlimab on breast cancer cell invasion, and the results showed that both 175 and 350?mg/ml of leronlimab can effectively block MDA-MB-231 cell invasion (Fig. 4c, d). Thus, the pro-invasive effect of CCR5 can be abrogated by a humanized monoclonal antibody to CCR5."

...
*"*Leronlimab prevents breast cancer cell metastasis in a mouse lung metastasis model

Leronlimab blocks breast cancer metastasis in vivo. In view of the finding that CCR5 inhibition by leronlimab reduced calcium signaling and cell invasion*, we determined the in vivo effect of leronlimab on the formation of lung metastasis. As a form of control, maraviroc was deployed as previously described. We used MDA-MB-231 cells transduced with the Luc2-eGFP lentiviral vector (MDA.pFULG cells) as an experimental metastasis model. The codons within the Luc2 gene in this vector have been optimized for the expression in mammalian cells, and therefore, mammalian cells expressing this reporter are 10 to 100 times brighter than the unmodified Luc gene. After injection of MDA. pFULG cells into the tail vein of mice, noninvasive BLI enabled the early detection of breast cancer metastasis. Weekly BLI was conducted for 8?weeks, and the radiance antemortem was used as a surrogate measurement of tumor burden. The dose of leronlimab was based on the bioequivalent dose shown to be safe in patients with HIV (700?mg) and the dose previously used to treat GvHD in mice.* Mice treated with leronlimab (2?mg/mouse) or maraviroc (8?mg/kg twice daily) showed a significant reduction in the volume of pulmonary metastases compared with vehicle-treated mice at 8?weeks (Fig. 5a, b, 860?×?106 (n?=?22 mice) vs. 3.7?×?106 photons/s/cm2/sr (n?=?6 mice) for leronlimab, vs. 0.4x ×?106 (N?=?7) for maraviroc). Leronlimab reduced lung metastatic burden >?98% at 8?weeks (99.6%). Collectively, these results provide evidence that the CCR5 antagonist leronlimab reduces the formation of lung metastasis in a murine xenograft model*."*

r/Livimmune - Figure 5
Figure 5
"We conducted a histological analysis of the lung metastases from the mice post-mortem. In order to determine the relative area of the lung occupied by metastasis at death in the mice that were either treated with leronlimab or unreated, the mice were euthanized and the lungs analyzed after paraffin embedding. Longitudinal sections (4 µm) of the entire lung were obtained every 100?µm and stained with hematoxylin and eosin. Each section was evaluated to identify lesions and to differentiate lesions from other space-occupying alterations including consolidation and inflammation. The region of lung metastasis for each animal was quantified in a blinded fashion using Fiji ImageJ, and the mean data were compared as mean?±?SEM for N?=?5 separate mice (Supplemental Figure 5 (see Additional file 1)). These studies showed that the mean tumor size was significantly reduced in the leronlimab-treated mice*."*

...

*"*Leronlimab enhances cell killing by DNA damage-inducing chemotherapy agents used for breast cancer treatment

Because CCR5 has been shown to activate DNA repair pathways*, we investigated the potential for* leronlimab to sensitize breast cancer cells to DNA-damaging agents*. To test this hypothesis, we treated MDA-MB-231 cells with* doxorubicin, a topoisomerase II inhibitor that induces DNA damage, together with either leronlimab (Fig. 6a) or maraviroc (Fig. 6b)."

r/Livimmune - Figure 6
Figure 6
"Leronlimab enhances the cell death induced by doxorubicin, a DNA damage-inducing chemotherapy agent. a MDA-MB-231 cells were treated with 10?µg/ml of leronlimab combined with different dose of doxorubicin for 3?days. The MTT assay was used to determine the relative cell number. The relative absorbance is shown as a fraction of the untreated control. The normalization of leronlimab-treated cells was to leronlimab with no doxorubicin. In b, the cells were treated with maraviroc (100?mM) combined with different doses of doxorubicin, used as a positive control. Data are shown as mean?±?SEM for N?=?8"

...

"The rationale for the current studies includes evidence that CCR5 may participate in the metastatic progression of breast cancer. In the current studies, we show that the humanized monoclonal antibody leronlimab efficiently blocks ligand-induced Ca2+ signaling, cellular invasion, and tumor metastasis*. Prior findings had shown that CCR5 small-molecule antagonists (maraviroc and vicriviroc) block metastasis of human breast cancer xenografts (MDA-MB-231 cells). The current studies extend these findings by demonstrating the humanized monoclonal antibody to CCR5,* leronlimab, efficiently bound CCR5 expressed on human breast cancer cells, blocked ligand-induced Ca2+ signaling, and inhibited Matrigel invasion of breast cancer cells. Furthermore, leronlimab reduced tumor metastasis in immune-deficient mice. In a subset of mice with established TNBC lung metastasis, leronlimab reduced the metastatic tumor burden and increased overall survival*. As leronlimab has been well tolerated in the HIV patient population without significant drug-related adverse events, the current studies suggest leronlimab may have clinical application."*

...

"The current studies extend prior studies demonstrating the importance of CCR5 in breast tumor metastasis prevention and by showing for the first time a reduction in the volume of established metastasis with life extension. The requirement for CCR5 in oncogene-induced cellular proliferation was supported by transgenic studies in which MMTV-PyMT-induced mammary tumors were reduced in CCR5-/- mice. Multiple CCR5-mediated pathways may contribute to tumor progression including MDSC, vascularity, and lymphangiogenesis*. CCR5 siRNA did not reduce the metastatic phenotype of MDA-MB-231 cells in the absence of additional MDSC, endothelial cells produce CCL5, and augmented breast cancer metastasis in another study. In addition,* CCR5 inhibitors also reduced lymphangiogenesis in triple-negative breast cancer (TNBC) cell line xenografts*. Other approaches to restrain tumor metastasis via CCR5 inhibition include targeting CCL5 in the bone marrow via nanoparticle-delivered expression silencing, in combination with maraviroc, which augmented anti-tumor immunity.*
...

A substantial number of studies have provided evidence in other systems that CCR5 participates in the important anti-tumor immune response. In the current studies, leronlimab restrained the development of tumor metastasis in murine xenografts in Nu/Nu mice which lack functional T cells. The nude mouse (nu or Hfh11nu or Foxn1nu) lack a thymus due to a mutation in the FOXN1 gene. The absence of a thymus means that there is no production of T cells; therefore, they are unable to activate the different types of immune responses (adaptive) during the implantation of cancer cells. These mice lack antibody formation, cell-mediated immune responses, and delayed-type hypersensitivity responses but produce NK cells, resulting in a reduced capability of killing virus-infected or malignant cells. Our studies suggest therefore that T cell participation is not necessary for the anti-tumor function of leronlimab observed in the current studies but do not exclude a potential role for NK cells which express CCR5*. Furthermore, as leronlimab is a humanized antibody that does not bind murine cells, it is most likely* the effect seen with leronlimab is mediated directly on the human breast cancer cells, rather the local murine tumor environment. That said, evidence supports a model in which additional immune functions are regulated by CCR5 and T cells in other settings. CCL5 recruits CCR5-expressing TAMs. T cells participate in the anti-tumor immune responses, in part through CCR5-dependent regulation of macrophage differentiation. The recruitment of immune cells, including tumor-infiltrating lymphocytes (TILs), MDSCs, tumor-associated macrophages (TAMs), innate lymphoid cells (ILCs), Tregs, mesenchymal stem cells (MSCs), and immature dendritic cells (DCs), contributes to tumor-induced immunosuppression. Many of these cell types express CCR5 and/or produce ligands for CCR5. Prior studies showed the small molecule CCR5 inhibitor maraviroc reduced MDSC-induced colon cancer metastasis. In the phase 1 pilot MARACON study, patients with advanced-stage metastatic colorectal cancer that were refractory to current therapies were treated with maraviroc. CCR5 inhibition correlated with reduced proliferation and an anti-tumoral macrophage polarized M1 morphology, although more complex interactions occur with PD-1- and CTLA-4-positive cells surrounding tumors with patchy CCR5 expression.
...

It is likely that CCR5 plays a broader role in governing cancer metastasis as maraviroc and vicriviroc reduced prostate cancer cell metastasis to the bones, brain, and viscera in immune-competent mice and reduced metastasis or cellular migration in glioblastoma and a variety of other malignancies. Prior studies had shown that CCR5 induces cancer cell homing to metastatic sites, augments the pro-inflammatory pro-metastatic immune phenotype, and enhances DNA repair, providing aberrant cell survival and resistance to DNA-damaging agents. The current studies, showing a reduction in the volume of established breast cancer metastasis with life extension, provide support for a controlled clinical intervention study using leronlimab in patients with TNBC.

Conclusion

Our studies show that the humanized monoclonal antibody, leronlimab, directed to the G protein-coupled receptor, CCR5, can both prevent breast cancer metastasis and reduce established metastasis. As CCR5 is expressed on the surface of breast cancer cells and leronlimab reduced CCR5-dependent cell-autonomous functions, including calcium signaling and cellular invasion, the impact of leronlimab in this case is likely mediated via a direct effect on the breast cancer cells. The studies were conducted in immune-deficient Nu/Nu mice, suggesting certain immune functions are not necessary for the action of leronlimab on TNBC metastasis in vivo. Leronlimab is administered as a weekly subcutaneous injection and has been used in more than 800 patients with HIV, without serious adverse events related to the drug. Together these findings suggest additional clinical studies of leronlimab in metastatic human breast cancer are warranted."

Tiny-Ad-8280

🚨 25¢ Stock. Stage 4 Cancer. 36+ Months Cancer-Free. Do the Math. 🚨
Let me tell you a story that shouldn’t be real — but is.

A story about terminal cancer patients who were supposed to be dead by now…
But instead, they’re alive. And cancer-free.

The company? CytoDyn ($CYDY) — a tiny biotech stock trading at just 25 cents.
The drug? Leronlimab.
And the data it’s about to present on May 15th at Europe’s biggest cancer conference (ESMO) might change everything.

Here’s what every investor — and every human — should know:

🧬 First, What Is Stage 4 mTNBC?
Let’s break that down:

Stage 4 = metastatic cancer — it’s spread from the breast to other organs like the brain, lungs, or liver.

mTNBC = metastatic triple-negative breast cancer — the most aggressive, deadliest form. It doesn’t respond to hormone therapy or HER2-targeted drugs. There’s no known cure.

Once you reach stage 4 mTNBC, the median survival is less than 12 months.
Let’s be real: Most patients don’t live a year.

🧪 Then Came Leronlimab
CytoDyn ran a small trial with 30 patients who already failed other treatments.
Many had cancer in their brain, liver, and lungs. They were out of options.

Here’s what happened:

All 30 patients (mixed doses):

Median overall survival (OS): 6.6 months

Median progression-free survival (PFS): 3.8 months

🧠 PFS = how long the cancer stays stable before it gets worse.
OS = how long people stay alive.

But then they zoomed in on 19 patients who got higher doses (525–700mg):

Median OS jumped to 12+ months

Median PFS rose to 6.1 months

❗️12+ means they were still alive at the time — they couldn’t even finish calculating it.

💥 The Bombshell: 36+ Months Cancer-Free
Fast forward to 2025.

CytoDyn got follow-up records after resolving a dispute with their old CRO (Amarex). What they found?

“A small group of patients… survived more than 36 months after receiving Leronlimab… and currently identify as having no evidence of ongoing disease.”

Read that again.

These were terminal cancer patients — not just surviving, but alive three years later with zero signs of cancer.

Not "slowed down." Not "in remission."

🎯 Cancer. Free.

🤔 What’s a “Functional Cure”?
It means the patient isn’t just surviving — they’re living a normal life, no signs of cancer, no progression.

In stage 4 mTNBC, that’s never been done before.

This isn’t about managing cancer. It’s about potentially beating it.

🥊 How Does It Compare to Trodelvy?
Trodelvy is another mTNBC drug.
Gilead bought it for $21 billion in 2020 after it showed:

Median OS: 11.8 months

PFS: 4.8 months

That was considered a major success — and it should’ve been.

But Leronlimab?

Has patients alive 36+ months

With no signs of disease

And median OS still growing

It’s not just a different league — it’s a different universe.

🧠 Why May 15th Matters
That’s when the world sees this data.
At ESMO Breast Cancer 2025 in Munich.

Dr. Richard Pestell — world-class oncologist (ex-J&J and Pfizer) — is presenting it.

And yeah, it’s a “poster” presentation.
But so was Trodelvy’s first public showing.

👉 Poster sessions are where Big Pharma scouts its next buyout.

💡 TL;DR — Send This to Your Group Chat
Stage 4 mTNBC = death sentence. Median survival is <12 months.

Leronlimab = 36+ month survival. Cancer-free. Possibly a functional cure.

Trodelvy got a $21B deal with 12-month survival.

Leronlimab’s median OS can’t even be calculated yet… because patients are still alive.

This gets revealed to the world on May 15th.

The stock? Still trading for just $0.25.

🔥 Final Thought
If this data holds up, it’s not just the biotech story of the decade…

💣 It might be one of the biggest medical breakthroughs in human history.

Because for the first time ever, we might be seeing a drug that functionally cures terminal cancer.

And it’s hidden inside a penny stock almost nobody is watching.

May 15th will tell the world.
Until then… do your homework.

https://journals.asm.org/doi/10.1128/jvi.02018-24

Addition of a short HIV-1 fusion-inhibitory peptide to PRO 140 antibody dramatically increases its antiviral breadth and potency

LOL. It is coming though.

Tiny-Ad-8280

🚨 The ESMO Poster Drop Is Real — But What Does It Mean for CYDY? Deal? Delay? Let’s Set the Record Straight. 🚨
We’re 7 weeks out from one of the most pivotal events in CytoDyn’s history — the ESMO Breast Cancer Conference (May 15) — and the company just locked in poster #369P, confirming that Dr. Richard Pestell will present data showing long-term survival in mTNBC patients treated with Leronlimab.

Sounds like a big deal… but people are confused. Is this just another “meh” biotech event? Or is something bigger brewing?

Let’s break it down — clearly, factually, and with all the details to avoid speculation and Reddit rumors.

🧠 What’s Being Presented?
The abstract title says it all:

Improved Long-Term Survival in Patients with Metastatic Triple-Negative Breast Cancer Following CCR5 Antagonism: A Case Series

We already know from the March Shareholder Letter that these are stage 4 mTNBC patients who had failed prior treatments, and some of them are now alive 36+ months later, cancer-free.

That’s radical, given the median survival in this population is around 12 months with the best drugs out there (e.g., Trodelvy).

This isn’t about tumor shrinkage. This is about people still alive — and NED (no evidence of disease) — three years later.

🧬 Why Haven’t They Released the Mechanism of Action (MOA) Yet?
Because ESMO rules prohibit full public disclosure of new clinical data before the abstract is officially presented.

That includes:

Final survival stats

Scientific interpretation

MOA explanations (like why Leronlimab works the way it does)

If they disclose too much, they risk getting disqualified from the conference. These are standard practices at major conferences like ESMO and ASCO — not a CYDY issue.

So yes — they’re holding the biggest cards (MOA + full survival data) until May 15.

💰 Why People Are Whispering About a Deal Before ESMO
Let’s be clear: there’s no public evidence of a deal in place.

But here’s why some believe a pre-ESMO deal is possible (though not guaranteed):

CYDY hasn’t raised money since releasing the survival data in February. That’s unusual for a small biotech. Most would raise ASAP on any good news to extend runway. That they haven’t may suggest they’re expecting non-dilutive capital (i.e., a partner or license deal).

They just formed an Oncology Advisory Board. That’s a classic move companies make when preparing for deeper clinical strategy — or partnership alignment. You don’t do that for fun.

Quote from the March Shareholder Letter:

“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.”

That’s not a throwaway line. That’s teeing something up.

Again — none of this confirms a deal before May 15. But it explains why some investors are speculating that things could happen before the data goes public and Big Pharma competition gets a chance to react.

Because once that data drops? It’s public. And if it’s as good as we think, the bidding war starts.

🧠 Reminder: This Is Exactly How Trodelvy’s $21B Journey Started
In 2018, Immunomedics dropped mTNBC survival data at ASCO (just like this).

It was also a poster.

Gilead came in 2020 with a $21 billion acquisition.

Leronlimab could be showing even better survival than Trodelvy’s 12 months. If true, this is the kind of data that moves mountains.

🧾 TL;DR (for the scrollers)
Leronlimab’s cancer data is going public at ESMO May 15

Poster is confirmed and presented by Dr. Pestell — a heavyweight oncologist

mTNBC patients: stage 4, treatment-failed — now alive 3+ years and cancer-free

MOA being held back for ESMO due to strict abstract rules (not secrecy)

They haven’t raised cash = maybe expecting upfront money from partner?

Oncology Advisory Board formed = prepping for scale

Reminder: Trodelvy started the exact same way (poster ? $21B exit)

This isn’t hype — this is what real biotech inflection points look like.

May 15 is the day the world finds out. But don’t be shocked if Big Pharma moves before then.

Strap in. 🚀

MGK_2

This Mechanism Screams Succumb No More
Greetings to All of You. Welcome here.

I suspect this post becomes a study, but I'll try to keep it intriguing.

Way back, I did a bit of analysis on CytoDyn's mTNBC Clinical Trial. Here are some of these posts:

Points taken off latest PR on TNBC

Improved Comparison of the previous PR on 7/19 and The Compassionate Use Study of LL in BC

My thoughts on the possibility of BTD for LL on mTNBC

Understanding the Significance of 3,600% Improvement in Overall Survival

In Preparation for the Coming Results on mTNBC

I want to try to get to the heart of the matter, as to why some patients who were treated with leronlimab for mTNBC ended up having extended Overall Survivability exceeding 36 months and going on 4 years now with no evidence of any existing tumor or metastasis.

It would be helpful to understand what in fact is happening and I know this information is forth coming as Dr. J said, but maybe we could try to figure out the general means by which this potentially happens for our own benefit. Here are some statements by which Dr. Lalezari has expressed CytoDyn's forthcoming disclosure of their newly understood Mechanism of Action:

"Looking ahead, we are excited to share more about the clarity forming around the putative mechanism of action of leronlimab in solid tumors...

...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.

...The exciting survival outcomes announced in February 2025 provide early clinical evidence of leronlimab’s potential impact across the field of solid-tumor oncology. As previously announced, we’ve submitted our findings as an abstract to the European Society for Medical Oncology meeting in Munich, Germany in May 2025. We are eager to share additional insights into the apparent mechanism behind the survival outcomes and will do so once appropriate and in compliance with pre-conference publication and announcement allowances. In the meantime, CytoDyn has initiated a follow-up protocol so we can continue to monitor the surviving patients into the future.

...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."

Getting to the root of what leronlimab actually is, it is a monoclonal antibody specifically designed to block CCR5, primarily & initially designed to prevent HIV from entering the CD4 T-Lymphocyte thereby preventing HIV replication. The unforeseen outcomes of blocking CCR5 turned out to result in many more positive purposes and indications which were never planned for. Now, it seems to be the case that some of these unintended effects of using leronlimab leads to a prolonged overall survival time which follows treatment of mTNBC. The same prolonged OS could also be another similar unintended but welcome consequence of leronlimab in the treatment of any/all metastatic tumors that depend upon CCR5 to metastasize.

Now, it could be ascertained, that many of the patients under treatment with leronlimab for their mTNBC, could also have that same extended Overall Survivability OS. What is interesting is that these patients, almost immediately upon the initiation of treatment with leronlimab, begin to feel much better right away. Although their tumors exist at the outset of treatment, possibly even raging, the patients themselves begin to feel better, rapidly improving; they recognize the near immediate subsidence of their tumor's disseminating rage. So that encourages them to be compliant and continue taking their leronlimab treatment as scheduled. Over time, their symptoms do dissipate as does the magnitude and quantity of their tumors. Their tumors shrink in size and reduce in number while they themselves feel stronger and improved to the point of approaching normalcy. What is now understood is that after their treatment period has been completed, their tumors do not return. Why not? That is the point of this.

Why do these leronlimab treated tumors not return? Patients or family members of the patients that take the medication do immediately recognize upon the initial dose of the medication, that the medication is quite readily working by their quickened response and improvement of symptoms. They form an inherent notion that the medication is doing what it has been intended to do. They know this assuredly when subsequent CTs or MRIs radiographically, (Our Friend is Still Alive), depict that tumor quantity and magnitude have diminished. When blood serum labs are drawn and their CTCs and CAMLs have dropped to zero, they know assuredly that their cancer is dying, no longer spreading, and that their tumors are vanishing.

Was Dr. Chris Recknor onto some other Mechanism of Action that Screamed Succumb No More when he discussed in the 6/30/2022 Conference Call how the CCR5 blockade leronlimab has other profound effects upon other chemokines and could thereby lead to other unknown but wanted effects?:

"28:30 Chris Recknor: These chemokines act as a beacon to attract other cells in the area. The difference is really big because we thought we just worked on CCR5, but we are also working on CCL2, 3, 11 and 18. In NASH studies, we can see correlation b/w CCL3 which is Macrophage Inflammatory Protein Alpha 1 levels and they increase in severity of NASH on biopsies. So patients in full blown NASH, show highest levels of CCL3, but leronlimab reduced CCL3 with 350mg compared to placebo from baseline from week 14. CCL2 is another one that moves monocytes, called Monocyte Chem-Attratic Protein and is a key biomarker associated with NASH. Leronlimab reduced mean CCL2 from baseline to week 14 in 350mg group compared to placebo.

Now when dr. Chung was talking about HIV and NASH, this has great application, because CCL2 applied to the treatment of the HIV patients is important because lower CCL2 levels correlate with less viral replication in effect to macrophages, less rapid feeding, of the latent HIV reservoir and less chance HIV central nervous system invasion. The ability to reduce CCL2 may have application to HIV and NASH and may really position leronlimab very effectively now to outpatients.

One other key biomarker is molecule Vascular Cell Adhesion Molecule VCAM is very important because VCAM allow immune cells to migrate through blood vessel walls. We did not know that leronlimab reduces VCAM until NASH, but now we have now observed a reduction from mean change to baseline in week 14 for the NASH 350 mg for VCAM and this is important because it has application to other inflammatory markers that are reduced. So further trials need to be conducted with larger numbers, but the exploratory biomarker analysis may be very relevant for informing about future research in other disease states including cancer. Dr. Kelly can you provide an update in oncology."

and immediately thereafter, Scott Kelly chimes in:

"32:20 Dr. Scott Kelly: Yes, Chris Recknor left with a perfect thing about VCAM b/c we do believe VCAM is important for oncology in leronlimab. What we are doing now, we are currently evaluating opportunities KOM Smithing ford, in mTNBC program for leronlimab in combo with a current SOC as well as colon cancer trial, we have animal and human data for mTNBC as well as animal data on the effects of leronlimab on colon cancer."
...
"36:07 Dr. Scott Kelly: We are very encouraged by the fact of leronlimab on the biomarkers and NASH. Many of these same biomarkers are supported by the literature to be important in our oncology program including CCL2, CCL5, CCL18, VCAM and VEGF. Some of these biomarkers also correlate with the potential to decrease metastasis, control the tumor microenvironment and correlate with antifibrosis"

Told ya this would be a study.

Remember, though all of this is only appreciated through the analysis of lab work on a patient, thereby drawing test tubes of blood and then analyzing, the phenotypic outcome of all of this is actually physically expressed in the improvement of these patient's symptoms, by their return to normalcy, which we can readily and immediately appreciate. But for purposes of Scientific Analysis and Comparison, these Biomarkers and Surrogates are used to understand how well the patient is doing, simply by knowing the value of the laboratory results.

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

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

July 19, 2021 06:00 ET | Source: CytoDyn Inc.

VANCOUVER, Washington, July 19, 2021 (GLOBE NEWSWIRE) -- CytoDyn Inc. (OTCQB: CYDY) ("CytoDyn" or the "Company"), a late-stage biotechnology company developing leronlimab, a CCR5 antagonist with the potential for multiple therapeutic indications, announced today strong preliminary results from its Phase 1b/2 trials and compassionate use with a total of 30 metastatic triple-negative breast cancer (mTNBC) patients. Patients in Phase 1b/2 were treated with leronlimab in combination with carboplatin.

Key findings from the interim 12-month analysis include the following:

72% of patients had a decrease in CAMLs (cancer-associated macrophage-like cells) ~30 days after induction of leronlimab

The decrease in CAMLs was associated with:

A ~300% increase in mean progression-free survival (mPFS)

A significant ~450% increase in overall survival (OS) at 12 months

High CCR5 in tumor tissue biopsies may help to stratify patients likely to progress on leronlimab

Decreases in CAMLs and CTCs (circulating tumor cells) appear to be related to slower progression and lower mortality

CAMLs appear to identify populations that are responding to leronlimab

Daniel Adams, Director of Clinical Research & Development, Creatv MicroTech, Inc., stated, “While these are only interim results at the 12-month point, our ability to rapidly monitor and identify patients that appear to respond to leronlimab using a single tube of blood is quite an encouraging finding. The fact that greater than 70% of patients saw positive changes in circulating tumor cells after a single dose of leronlimab was made even more informative by their dramatic increases in both progression-free survival and overall survival. The fact that a large group of patients taking leronlimab had an mPFS of approximately 6 months is well beyond that experienced with current treatment options available to these women, who typically have mPFS of approximately 2 months. This result is even more amazing as these women did not even reach mOS in 12 months, considering the typical mOS in this population is only 6 to 7 months.”

Scott Kelly, M.D., CytoDyn’s Chief Medical Officer and Chairman of the Board, commented, “We are very excited about these preliminary results and are eager to discuss the next regulatory steps based on this data. Based on leronlimab’s mechanism of action, we believe these results may provide tangible hope for patients suffering from mTNBC, and potentially other forms of cancer. As we have said previously, we believe CytoDyn will evolve into an oncology-focused company as well as other potential indications.”

So, all of this is not just fantasy or theoretical for that matter, but rather, it is 100% real and the data shall be presented at ESMO in mid-May. But, on the topic of reality, I see the need to ask whether it is actually real or not to actually expect that many of those who are treated with leronlimab for mTNBC or for that matter, any CCR5 dependent tumor, to actually expect an OS of 36 months or more? Is it also a reality that this theory be applied to any other CCR5 dependent cancer under treated by leronlimab? As we have already reviewed, that with this particular test, we can know who responds well and who doesn't respond well to treatment of mTNBC with leronlimab.

"CytoDyn now has verified a testing method to assess within the 1st Treatment Cycle, (28 days), whether or not the current method of treatment would be successful in improving the patient's progression free survival and overall survivability or if the current method of treatment would result in a worsened progression free survival and a worsened overall survivability.

If you have a decrease in CTCs in the 1st 28 days, the patient would benefit from current treatment.

If you have an increase in either CTCs or CAMLs, the patient would not benefit from current treatment.

[If CTCs and CAMLs are both 0 for (2) months in a row, treatment may be stopped as the patient is likely cured.

If evidence of the cancer returns, another round of full blown treatment should immediately be initiated]."

We already know that for leronlimab to work, there must be some CCR5 dependency of the tumor, which means, that the specific tumor in question, depends upon the presence of some quantity of CCR5. This means that, if CCR5 were not present, then the tumor itself would also not be present. Either the tumor or the surrounding microenvironment is mandatory to possess some quantity of CCR5 for the tumor to proliferate. Without that presence of CCR5, leronlimab would accomplish nothing in such a milieu. However, given that some quantity of CCR5 is present with in the tissues of the tumor or tumor microenvironment, then leronlimab has the potential to deliver the stated results of 36 month and growing OS. But why? or How does it do this if it is not present and not being administered?

Leronlimab delivers this killing blow to the tumor of course, when it is being administered to treat the patient. However, when the treatment period is over and done with, leronlimab then, is no longer being administered. So then, during the time period which follows the treatment period, is leronlimab still doing anything of note? Considering these recent findings of 36 months and growing of Overall Survivability, the question posed is a valid. Is leronlimab still at work or has leronlimab induced some permanent changes or only long lasting changes which make it impossible or less likely for that specific tumor to proliferate in that patient's body? I think we shall soon learn what CytoDyn definitively believes or understands to be true, possibly even prior to the start of ESMO in mid-May, but I lay out below, some hypotheses I make.

One consideration might be that it is almost as if during the treatment period, leronlimab somehow, in a sense, places a lock and key over the CCR5 receptor. That over the course of treatment with leronlimab, the CCR5 receptor becomes somehow transformed and no longer remains capable of enabling the tumor to proliferate; or that the tumor no longer remains sensitized towards CCL5 RANTES; or that the CCR5 receptors no longer remain sensitized to the CCL5 RANTES ligand.

Or what if, because of leronlimab's effect on the tumor, the tumor somehow mutates and starts producing a mutated form of RANTES, CCL5, in an attempt to get around leronlimab's thwarting effects. Such that RANTES itself might have a higher affinity for CCR5 than leronlimab itself, however, with the tumor creating that mutation in response to treatment with leronlimab, RANTES itself becomes deformed and now no longer even attaches to CCR5?

If any of this were to possibly happen, then, the same, extended Overall Survivability would result with no evidence of disease progression.

What if dormant cells of the tumor actually wake up 4 years or 48 months later, and attempt a comeback, a return of power, now using a less sensitized or de-sensitized version of CCR5 or a deformed or transformed CCL5 RANTES, its comeback would only be a weakened incursion. In addition, the patient's own immune response would be highly sensitized and attuned against any return of that specific tumor because of the memory it established from the initial tumor. The killer T-Cells would hone in on and quickly shut down any return of those specific tumor cells attempting to return. That is because 4 years earlier, when the tumor was originally raging, and when leronlimab was initially administered, leronlimab had permitted, allowed, enabled and enhanced the full flawless functioning and deployment of the patient's immune system even though their symptoms had seemingly improved. The weaponry specifically developed against this tumor were all being created for future use. Over the course of the initial treatment period, the patient developed an unassailable Immunity against that specific tumor such that any subsequent revitalization of the dormant tumor cells or even return of any new identical tumor cells which follow the tumor's initial eradication, would be immediately shut down by a vicious onslaught which is conducted by the totality of only those specifically manufactured immune defenses meant only for this purpose.

The following details what happens without leronlimab treatment and could explain why the current SOC Trodelvy does not have a 36 - 48 month OS.

"After breast cancer treatment, dormant tumor cells continue to lay in wait in some patients. These so-called “sleeper cells,” also referred to as minimal residual disease (MRD), can reactivate years or even decades later. Once the cells begin to expand and circulate in the bloodstream, it can lead to the spread of metastatic breast cancer. Patients who have MRD are more likely to experience breast cancer recurrence and have decreased overall survival."

Another possibility could be that leronlimab immediately induces an inherent change within a protein or a cell or within a group of proteins and/or cells in the immune system of every patient with CCR5 within their tumor microenvironment. As soon as leronlimab is given, that immune system change is immediately made leading to the improvement in symptoms and over time, that change is strengthened, reinforced and perfected such that by the end of the treatment period, the tumor is no longer able to proliferate whatsoever and is then quickly resorbed by the body.

However, should the tumor somehow break free of its resistance, or is somehow permitted and escapes so as to come forth in the body, then, the body's own defenses which were originally developed from the initial leronlimab treatment period would begin to battle against the tumor. But, given the fact that the tumor in fact had the capacity to overcome the body's own defenses to somehow arise again, then the body's own defenses would then be insufficient against the tumor and to stop the tumor from proliferating, would require another treatment round of leronlimab dosing to again suppress the tumor once and for all from proliferating. This type of tumor that can somehow, overtime, return back again, is of very virulent disease, and is unwilling to conform to just one round of this defense.

However, with a second treatment round of leronlimab, the tumor would again be shut down and this time for good, never to return. All of this is visual. All of this happens before our eyes, as we watch the tumors melt and shrink away, but it happens over an extended period of time and it is not yet understood exactly how or why, but that day is coming to know the how and the why of it.

Or Is the Placebo Effect at work? Knowing that you've been treated with leronlimab for some time, do you simply believe yourself cured placing you at the epitome of health? And by believing, do you simply will yourself into feeling good and into being cancer free by willing your own Immune defenses to be ready, willing and activated to fight on your behalf?

"Creatv have the software which count CTC circulating Tumor Cells or Metastasis. [I would think that at ESMO they will be touting their software while discussing these Overall Survivability results of 36-48 months.] [Remember mTNBC metastasizes to the brain.] Leronlimab obliterate tumors period. Leronlimab knocks out VEGF, angiogenesis and prevents metastasis, dries up tumors and blood vessels. Leronlimab crosses the BBB, so it dries up tumors in the brain too. MD Anderson knows.]

---

this is amazing from the 10-k, page 7-8.

One patient was administered leronlimab with stage 4 HER2+ breast cancer with metastasis to liver, lung, and brain. The patient received her first dose in November 2019 and remained on study drug until spring 2022
Brain Metastasis. Liver, Lung metastasis. No PD1 or PDL1 inhibitor at all. She was on Leronlimab nearly 30 months. 2.5 years on Leronlimab with Brain mets.

30 month overall survivability for this patient. If that's when she died.

·From the FB page:
In my humble opinion something big is coming In cancer.
1. They put together an oncology board out of the blue.
2. The letter started with cancer & ended with “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 & are executing on that vision”.
3 “ leronlimab could play a significant role as a paradigm-shifting therapeutic in oncology”
4 “This is only the beginning of the Company’s 2025 oncology story”
5 “the developments in oncology have set the stage for 2025 to be a benchmark year for CytoDyn”
6 They are excited to share the results but can’t until after the ESMO conference.
7 They set up a new protocol to continue monitoring the survival patients
8 They began 2 preclinical’s in cancer & more importantly added a 3rd to “ further examine the apparent mechanism behind the observed increase in survival as compared to existing treatment paths”
9. Max’s post was all about mTNBC & not his HIV specialty
Buckle up!!

Lab_Monkey_

Leronlimab Treatment for Multidrug-Resistant HIV-1 (OPTIMIZE): a Randomized, Double-Blind, Placebo-Controlled Trial
This JAIDS article was just posted on the Publications page of the Cytodyn website. As has been stated before, the cadence of the release of information, and the delay of release in relation to the published date is very interesting. They are definitely a step ahead of the public sphere of knowledge.

Conclusions:
Leronlimab resulted in significantly reduced plasma HIV-1 within one week after addition to failing ART. After 24 weeks combined with an OBT, most participants had plasma HIV-1 RNA levels <50 copies per mL plasma, suggesting utility of leronlimab as a component of salvage therapy.

Yang, Otto O. MDd; Lalezari, Jacob P. MDf,g; Sacha, Jonah B. PhDh; Hansen, Scott G. PhDh; Meidling, Joseph MBAg; etal.

MGK_2

Advancement Forward, Behind The Scenes
Greetings Folks

Let's try to see a bigger picture. I speculate here based on what we know.

We've said this would take time. We've said that it is down the road a ways, that this could take a little while yet. This post may also confirm that understanding, I believe.

Here is a refresher of where I'm going, only, disregard the possibility that the 250 million shares were institutionally owned.

We have discussed in recent weeks, the potential of a collaboration, and I explained and reasoned why and how this collaboration could exist. The GF component is primarily tied to HIV. I have also indicated that the ViiV component would also be tied to HIV. But the GSK component could have multiple ties. That to HIV, Oncology, MASH, Alzheimer's, virtually everything that CytoDyn is pursuing.

"Our Strategy

We are a focused biopharma company. We prevent and treat disease with specialty medicines, vaccines and general medicines. We focus on the science of the immune system and advanced technologies, investing in four core therapeutic areas - respiratory, immunology and inflammation; oncology; HIV and infectious diseases – to impact health at scale. Our Ahead Together strategy means intervening early to prevent and change the course of disease, helping to protect people and support healthcare systems."

We have also made strong arguments considering Novo Nordisk as a possible licensee of Livimmune for the combination of Ozempic with Leronlimab targeting MASH and liver fibrosis. Eli Lilly is another one on the list for that same indication, but with the combination of Mounjaro and Leronlimab for MASH and liver fibrosis. I've discussed also in the past another possibility of Madrigal licensing Livimmune with the combination of Rezdiffra and Leronlimab for MASH and liver fibrosis.

But, let's take a look at some Parallel plays that could be happening behind the scenes. We know GSK is running a Pulmonary Fibrosis Pilot Trial at Boston University.

Essentially, as a result of the findings of the most recent murine study which are stated here:

"The third study, concluded in January 2025, [resulting in a p-value across all 3 studies < 0.01] evaluated reversal of liver fibrosis in mice who received carbon tetrachloride, a liver fibrosis-inducing agent, from birth to sacrifice at day 35.

“The management of patients with advanced liver fibrosis due to a variety of etiologies is an area of enormous unmet need in the field of hepatology. The results of these three preclinical studies support both the biologic activity and potential clinical benefit of leronlimab’s ability to bind to CCR5 receptors on hepatic stellate cells, leading to a reversal of established liver fibrosis,” said Melissa Palmer, MD FAASLD, the Company’s Lead Consultant in Hepatology."

we can therefore make the assumption that the Pulmonary Fibrosis Pilot trial is now Ongoing. I really love this trenddetector!! GSK teams up with the Center for Regenerative Medicine (CReM) at Boston University and Boston Medical Center. This Pilot Trial was contingent upon the determination of the fact that leronlimab certainly is capable of removing fibrosis regardless of its etiology, p-value < 0.01.

"London-based GSK is crossing the pond to form a new lung disease research collaboration with Boston scientists. The Big Pharma is joining forces with researchers from the Center for Regenerative Medicine (CReM) at Boston University and Boston Medical Center to develop new models for lung diseases like pulmonary fibrosis..."

So, if GSK is probably pursuing this promised Pulmonary Fibrosis Pilot Trial at Boston University at their own center, Boston Medical Center,

"As a side note, we have been contacted by colleagues at a major academic institution who indicated that, if the liver fibrosis reversal results are confirmed in the follow-up studies, they would be interested in funding a pilot study of leronlimab in the treatment of patients with pulmonary fibrosis at their own center."

Then, it would seem that the indication of fibrosis of any etiology may be divisible or separateable. Meaning that leronlimab may be licensed by various companies for the indication of fibrosis, but for Indications that would be separated based on organ type. Therefore, Pulmonary Fibrosis would be considered a separate indication from Liver Fibrosis which would be a different indication from Cardiac Fibrosis which would be a different indication from Kidney Fibrosis and a different indication from Pancreatic Fibrosis. Etc...

So, if GSK is not pursuing MASH, then, we can consider either Novo Nordisk, Eli Lilly or Madrigal for a licensing agreement with leronlimab to act as the anti-fibrotic in that combination treatment for MASH.

Let's go back to GSK. Not for MASH, but rather for MSS mCRC. I have to ask the question. Why has there been no discussion on the current progress of the Phase 2 Clinical Trial? At least nothing to speak of really? If there are delays, there has been no mention of them, or of any progress for that matter. I read an interesting post by Jake at Investor's Hangout, where he says:

"...CYDY management would much prefer to avoid the time and expense of building out a go it alone in-house drug development structure in favor of having a BP partnership/eventual BO doing that heavy lifting. In that vein, the fact that these 2 jobs remain open is consistent with the premise that an oncology partnership is on the near horizon."

So, what Jake is suggesting is certainly a possibility and if these (2) jobs he is referring to are not yet filled, though they certainly are necessary for the MSS mCRC Clinical Trial to proceed, could it be that CytoDyn's real intention all along was to proceed forward in this MSS mCRC Clinical Trial in a partnership with a large BP and not all alone? Yes, Very possible.

Could that explain the delay in hearing from CytoDyn? Maybe the NDA requires that enrollment be completed before making any announcement? Regardless, CytoDyn's number one Priority is MSS mCRC.

From Fulfillment:

"When Dr. Lalezari took his seat as CEO in December 2023, insufficient time had passed since Bevacizumab's maker's approval in the summer of 2023 to determine whether or not they would be interested in the proposed MSS mCRC combination trial, but in May of 2024, CytoDyn had worked out plans with Bevacizumab's maker to make this trial the #1 Priority. Now, based on leronlimab's MOA, we know the outcome really and how this should pan out. So, like AffectionateAd3095 says, Let's Move Forward and Get This Party Started. In a word, Fulfillment. This 1st contract gets the ball rolling which carries with it too much momentum to ever be able to bring it to a stop again."

So, if MSS mCRC is Priority #1, we can conclude that the likely partnership in MSS mCRC would be with GSK.

From A Panoramic View:

"...so if it were to be done in conjunction with another PD-1 blockade, then GSK could also be in the picture considering their 100% effective performance in mCRC with their dolstarlimab or Jemperli.

This dolstarlimab GSK study was performed only in patients with a certain genetic defect which thereby eliminated 96% of patients with mCRC from even being eligible for their very limited and specific patient population trial:

"all of the tumors had a gene mutation that prohibited cells from repairing DNA damage. These mutations are found in 4% of cancer patients. Pembrolizumab, a Merck checkpoint inhibitor, was given to patients in that experiment for up to two years. In around one-third to one-half of the patients, tumors shrunk or stabilized, and they survived longer. Tumors eliminated in 10% of those who took part in the study. The experiment needs to be duplicated in a much larger study, according to the researchers, who point out that the current study only looked at individuals with a unique genetic signature in their tumors."

Maybe, if GSK wanted to partner, leronlimab would make it possible for Jemperli to treat even those without that unique genetic signature. Leronlimab potentially could allow GSK's PD-1 blockade Jemperli to expand its reach in mCRC from only 4% of the MSS mCRC patient population who do have that genetic mutation to 100% of the MSS type mCRC tumors.

The point of all this is to show that something is happening behind the scenes in regards to MSS mCRC. In the past few months, I have shown that much has been happening behind the scenes in regards to HIV Cure, MASH and Fibrosis. I have been discussing HIV Cure, MASH and Fibrosis, but hardly any mention or discussion of MSS mCRC. Well this unexpected delay during the enrollment phase of the MSS mCRC Clinical Trial could be due to an NDA collaboration in this very trial.

We have said on many occasions that G is CytoDyn's arch rival. We have said that CytoDyn is darn close to an HIV Cure. That would be a devastating blow to G when CytoDyn makes that declaration themselves. We have said that 4 years of no evidence of cancer return is equal to a Cure. When CytoDyn proves this scientifically, that too would be a horrific blow to G's cancer treatment medication which they are intending for many types of cancers, not just mTNBC. Leronlimab's capacity against Fibrosis would not so much affect G at the moment, but in time, would minimize the need for G's drugs.

A Cure to HIV is very close. A Cure of mTNBC seems plausible. Certainly, an OS of 24 months is quite doable and that is a double of G's current 12.1 month OS. It already seems as if CytoDyn has a partner in HIV. I've explained that many times. The GF has already awarded Jonah Sacha nearly a million dollars for his work on the HIV Reservoir. How many more grants like that one are coming down the road? There is more work to do regarding Triple Therapy and more work regarding the Placenta LS Mutations. LATCH is happening this year in (2) Clinical Trials. These advancements have the potential to utterly demoralize G. But all of this is very much still ongoing. Considering Max Lataillade, that partnership could very likely expand and morph into a collaboration between The GF, ViiV and GSK together with CytoDyn. We know GSK is pursuing Pulmonary Fibrosis at Boston University, precisely at the same time that CytoDyn was promised a Pilot Trial in patients at their own medical center, possibly Boston Medical Center.

In accordance with Jake's post, Given the delay in communications, I'm considering the possibility that an NDA could exist in regards to the MSS mCRC Clinical Trial that is currently ongoing. How helpful would that be if GSK were to partner somehow in this MSS mCRC Clinical Trial. Whether it is with Jemperli or not, their hand in the MSS mCRC Clinical Trial would be invaluable to CytoDyn. Their help would greatly subdue G's influence upon the outcome of this trial.

I don't believe GSK would bring Jemperli into this Clinical Trial because the protocol for this Clinical Trial has already been approved by the FDA having leronlimab in combination with trifluridine plus tipiracil (TAS-102) and bevacizumab in patients with CCR5+, MSS, relapsed or refractory mCRC. To include Jemperli, would greatly slow things down. If they wanted to include Jemperli, it could be done at a later point. Remember, in the mTNBC murine study, they are comparing leronlimab to Keytruda, which is Merck's PD-1 blockade, very similar to GSK's PD-1 blockade Jemperli. If they find strong evidence that leronlimab works synergistically with Keytruda, then, it very well may be synergistic with Jemperli as well.

"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, with these 3 indications, and the (organizations who may be involved in order of likelihood):

HIV: (GF, ViiV, GSK)

Fibrosis: (GSK, Novo Nordisk, Eli Lilly, Madrigal)

MSS mCRC: (GSK, Merck)

If any of this in fact is true, how close are we to that moment of disclosure? Well, if the MSS mCRC Clinical Trial is to progress beyond enrollment, then that disclosure would need to be made soon. We have said many times that GSK shares much in common with CytoDyn and they too may have found a way to get involved in the ongoing Phase 2 Clinical Trial of MSS mCRC. The trial was not originally written to include GSK or their drug Jemperli, but given the recent re-testing of Keytruda in combination with leronlimab against mTNBC, it becomes a possibility that there is synergy between a CCR5 blockade and a PD-1 inhibitor and that would greatly interest GSK.

GSK is a possible collaborator with CytoDyn in all 3 indications above. G would be an antagonist to each of the 3 indications above. G has been successful in stealing away any advancement CytoDyn has made in any indication. There are ways GSK could get involved without getting directly involved. They could lend a hand in the trial in ways which are not that obvious and those 2 jobs may not be fulfilled because GSK may be the intended recipient. What would be the motive? To protect the trial. To thwart any attacks made against the trial. To insure that the trial is conducted fairly, because CytoDyn hardly has the resources to insure this happens aside from its CRO Syneos Health.

Seems to me, GSK is in on all 3 of these indications. Does GSK have a beef with G? I think they might. Leronlimab has the potential to annihilate and G fears that, so they do what they can with what they have to prevent this, regardless of ethics. If G bought out CytoDyn, they would shelve leronlimab. Know this. That would be equivalent to a nuclear bomb placed on leronlimab.

Maybe GSK doesn't partner up regarding MSS mCRC, but they only help out for some agreed upon reason. I think CytoDyn can rely upon GSK for an assist in the event it becomes necessary, especially if G were the reason for that need. Maybe GSK would agree to outbid G if there ever was an offer by G, who knows, just speculating.

CytoDyn does come out with the Cure to HIV. CytoDyn does come out with the Cure to mTNBC. Leronlimab becomes the only drug that substantially reduces the fibrotic scarring of any organ that develops fibrosis. CytoDyn completes the MSS mCRC Clinical Trial obtaining statistically significant efficacy of leronlimab against MSS mCRC. All of this pushes G into a corner, with no where to go.

If you were G, how do you recover from all of that? You don't. If a Cure to HIV is established, is there any need any more for scheduled on going forever treatments? The same question is posed for mTNBC? By eradicating fibrosis, the degree of disease is greatly diminished. Why then would any treatment be necessary once the fibrosis is gone? If the same results are obtained in MSS mCRC that were obtained in mTNBC, then we can expect great results in MSS mCRC. In all of this, CytoDyn requires an assist, a partner. I think GSK is poised or most aligned with CytoDyn's own objectives and may even be playing somewhat of a protective role thereby giving Dr. Lalezari the confidence to say:

"I believe our current strategy will result in significant value return to the Company and its shareholders and should give us the opportunity to do so on an abbreviated timeline. We are on good terms with the FDA, we have the funds required to pursue our key development objectives and we have the requisite expertise and associations to execute on our vision. Entering 2025, the Company is in control of its own destiny."

Think again who they have: Max Lataillade, Melissa Palmer and Richard Pestell. These are individuals of great experience. Friends with the Gates Fund and with Emma Walmsley, CEO of GSK. Are they just sitting on their laurels?

Nice day guys. Looking forward to a gap up soon and moving forward from there.

Not celebrating anything. Just acknowledging the obvious. Someday CYDY will be able to hold a gain. In the meantime use the downturns to accumulate for the long term and if you have the balls for it, swing trade. That really has been the only way to make money these last few years. Stocks are vehichles for making money. If you want to support the companies research write a check and donate to the cause directly.

Looking forward to the news on Tuesday.

"The ONLY achievement for a biotech is a drug BLA or NDA approval (NOT a Right to Try or some research hack, NOT butt monkeys)."

Ridiculously simplistic viewpoint IMO.

https://www.linkedin.com/pulse/leronlimab-breakthrough-immunotherapy-farbefirma-qi4if

Leronlimab: A Breakthrough in Immunotherapy

Farbe Firma Pvt. Ltd.Farbe Firma Pvt. Ltd.
Farbe Firma Pvt. Ltd.
Injectables | Lyophilized | Liposomes | Nanoparticle | NDDS | Peptides | Microspheres | Emulsion | Suspension | Depot
Published Jan 22, 2025
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Introduction

Leronlimab is a humanized monoclonal antibody designed to target the CCR5 receptor on T cells. This innovative therapy aims to harness the body's immune system to treat various conditions, including HIV infection, metastatic triple-negative breast cancer, and severe respiratory complications associated with COVID-19.

Mechanism of Action

Leronlimab works by binding to the CCR5 receptor, which is found on the surface of certain immune cells. By blocking this receptor, leronlimab helps to modulate the immune response, making it a valuable tool in the treatment of diseases driven by excessive immune activation.

Clinical Research and Efficacy

Clinical trials have shown promising results for leronlimab in the treatment of HIV infection and metastatic triple-negative breast cancer. In HIV patients, leronlimab has demonstrated significant viral load reduction and improved immune function when used in combination with standard antiretroviral therapies. In breast cancer patients, leronlimab has shown potential in improving overall survival and progression-free survival rates.

Side Effects and Considerations

Common side effects of leronlimab include diarrhea, headache, swollen lymph nodes, high blood pressure, and injection site reactions. These side effects are generally manageable but require close monitoring by healthcare providers. Patients receiving leronlimab should be monitored for signs of infection and other adverse reactions.

Conclusion

Leronlimab represents a significant advancement in immunotherapy, offering new hope for patients with HIV, metastatic triple-negative breast cancer, and severe respiratory complications associated with COVID-19. Its ability to modulate the immune response provides a targeted and effective treatment option for these conditions.

Yep, bad few days that is for sure. Congrats.

Those NDA's are difficult to get around!

Not sure if this older video was ever posted here but it is worth a watch for those interested in how leronlimab works in cancer:

https://s3.amazonaws.com/content.stockpr.com/cytodyn/db/205/3059/video_mp4/cyto.mp4

Fidelity:

McLean Capital Management resumes coverage for Cytodyn with NEUTRAL recommendation.
Investars Analyst Actions - public
3:12 PM ET Mar-11-2025
On March 11, 2025 McLean Capital Management resumed coverage for Cytodyn (CYDY.NaE) with a NEUTRAL recommendation.

From a couple days ago MGK_2:

Abrupt Turnaround
I liked u/Biotrends_USA recent post Collaboration With BP?, so this is my response.

Shareholders need to wait until the event we've been looking for begins; once it starts, it's over. The interaction, the trading of shares exceeds all rational expectation. How does that happen? Bidding War or Governmental Intervention.

Doesn't it seem as if a standstill is at hand? Neither side is giving up. Almost an unsolvable dilemma. Tremendous resistance remains in opposition against this molecule, but the promises that this molecule provides exceeds the resistance poised against it. The resistance wants to crush, destroy and demoralize, by stealing away investments and hope placed in the molecule.

There is no way CytoDyn partners together with the Puppet Master G. That particular company which heads up the short campaign against CytoDyn has got to be a pharmaceutical, so therefore, how could CytoDyn ever trust its chief nemesis, its arch rival? It certainly can not ever trust them, so then how could it partner up with them?

The SEC is supposed to intervene in order to prevent illegal market manipulation tactics. Even the stock brokerage houses which facilitate these illegal short trades are complicit. A new administration has come, but so far, no changes have been appreciated.

If these attacks ever do cease, then the parties could come to the table to work things out. I don't have any hope in this solution. How can the memories of what has happened be forgotten, which is necessary to arrive at a deal? If they can't be forgotten, how can a deal be arrived at? Though CytoDyn settled for a rather low settlement in Amarex, did they really have a choice? To get more would have cost more time and money and how much more could Amarex even pay?

Looking forward, how then can CytoDyn ensure to be fully protected from the onslaughts of G in a partnership deal with anybody? The only real evidence of a partnership deal is from the GF. If G is truly against anybody partnering with CytoDyn, then how do they feel about any current investment into CytoDyn or into leronlimab, even if that investment is given to OHSU? If that investment is put towards solutions which G wants domination over? How does G feel about any investment / grant made towards finding the Cure to HIV? Clearly, they are opposed, and CytoDyn is such a small target, with such great rewards if defeated, that they make a perfect target for big old G to rampage.

CytoDyn is too small to be supported and defended by many of the big names, though CytoDyn's potential pipeline is quite rich. It can not be denied that by some unknown means, CytoDyn has found a way to survive. Because of its main resource, otherwise known as leronlimab, through some of its specialty shareholders, as well as its myriad of shareholders, CytoDyn has found that amazing means to remain afloat, despite the constant barrage of fire which persists against it, yet, CytoDyn remains vigilant in putting up its own offensive and fighting back. CytoDyn has built up an arsenal of weaponry focused on their targets, aimed and honed square upon the Cure to HIV, treatment for MSS mCRC, mTNBC, GBM, Fibrosis, MASH, Alzheimer's Disease, Chronic Fatigue Syndrome and on and on.

How do they achieve this? There are some liquid reserves from a settlement with Amarex, but much of its current pipeline is being driven by unknown sponsors who are willing to run Pilot Trials in the various indications listed above, all of which incur zero cost to CytoDyn. CytoDyn's only responsibility is to provide the leronlimab for those unidentified sponsored Pilot Trials.

Lalezari has kept a very low profile. He certainly does not tempt G. He must make an occasional PR or two, but, he does not flaunt his findings. In fact, he may even be trying to suppress what he would otherwise, rather exaggerate. Lalezari purposely tries to minimize CytoDyn's vulnerability. By exploiting possibilities before they are quite ready, that would increase CytoDyn's vulnerability. Lalezari therefore does the opposite. He wants that vulnerability be kept to a minimum, so he remains tight lipped. Rather silent. Why does he do this? I think the answer lies in the answer to the following question. How can he trust G at all?

Whoever is manipulating the market against CytoDyn is the same entity as who ever turned Amarex against CytoDyn and is the same as whoever ran the ambulance chasers. It is that entity who is the Puppet Master and they are still out there continuing day in and day out in constant opposition against CytoDyn's advancement. This Puppet Master isn't going to give any amount, not even an inch. But neither is CytoDyn.

CytoDyn has an obligation to its shareholders and to its resource leronlimab. The SEC should intervene to keep it a fair playing field, but they, so far have failed, but they are now part of a new administration and hopefully, changes are soon to be appreciated soon. G is absolutely not in favor of any pro-leronlimab Big Pharmaceutical to come to CytoDyn's aid. Therefore, this particular partnership information remains under lock and key via NDA and CytoDyn hasn't let out a peep. G is dead set against any collaboration CytoDyn might make with any Big Pharma as they see any collaboration as a much stronger antagonist against their own goals and ambitions of HIV treatment. It is absolutely G's desire that CytoDyn never partners, thereby keeping CytoDyn small enough, without any substantial financial backing, in order to keep it at bay with the inability to ever put up a real fight. To ensure that CytoDyn never has a means by which to advance, or to substantially and drastically slow down and retard CytoDyn's advancement efforts to reach their goal that would really hit G where it counts, which is of course a leronlimab approval. This really is the battle here. A never ending circle till one comes out on top. For G, it is money very well spent to prevent a leronlimab approval, because they know what the cost to them would be if leronlimab were approved.

G can't give up their life blood. They have all sorts of HIV treatments, ART, HAART, long acting agents and they also have a treatment for mTNBC. Leronlimab is a direct competitor for these indications. G can not lose this part of their business, because, this is their entire business really. But leronlimab is a direct threat to all of that and G knows this. I don't think G is willing to give up even one, because if leronlimab received approval in just one indication, it receives indication in all, because by "off label use", leronlimab, with its clean safety profile, would be patient requested for everything and doctors would be willing to prescribe it, as it would in fact heal and patients would pay directly for the medication for the no side effects benefit.

So therefore, G remains persistent in hampering CytoDyn. But CytoDyn also continues on with its own goals and ambitions, albeit more slowly. Slowly, but surely, leronlimab shall be shown superior to G's current treatments. Little by little, it shall be made known, that leronlimab is the superior medication in all these indications. Bit by bit, these indications are again put back into CytoDyn's pipeline, as is currently being done in the mTNBC indication. Doesn't it feel good that the GF has CytoDyn's back when it comes to HIV. But as for mTNBC, who has CytoDyn's back? GSK? Merck? What about in Fibrosis? Madrigal? Novo Nordisk? Eli Lilly?

These are some threats to G, but these possibilities pose another reason why G should double down and could be why they are currently doubling down. CYDY went from $0.45 back to $0.25 in just 2 weeks. The problem at hand, the dilemma we face, is difficult. Almost unsolvable. Neither side is willing to compromise or to give even an inch.

With CytoDyn remaining on its own, without the aid of a partnership or buyout, this battle goes on forever. It is a slow downward spiral by attritional forces imposed by G, but G must remain prepared for a long drawn out war because CytoDyn has many sponsors to bring this drug to its fruition. As I said above, the fight appears to be at sort of a standstill, where a stalemate could be arrived at with minimal advancements made either way, yet the piss poor fighting continues on and on to no end. No answer to it exists except for...

The fact that NDAs do exist. The fact that CytoDyn has NDAs in place but they are keeping that information close to their vest. The information regarding partnerships and licensures. When this information is publicly released, it then leads to a bidding war. The bidding for this tiny company subsequently increases. Yes, this tiny company with zero income, with a large load of debt, and a compromised reputation, receives a bid over and above the value set in the NDA. Yes, it has become obvious, that CytoDyn has successfully and unceasingly worked to restore its reputation and has also branched out in multiple indications, proving its only resource to be effective in a variety of indications, making it extremely attractive to many Big Pharmaceuticals.

Yes, this tiny company actually draws a higher price than its value set in the NDA due to a bidding war. It is either this or Governmental Intervention that begins the Abrupt Turnaround for CytoDyn. These are my possible answers to the current unsolvable dilemma. A bidding war and/or Governmental Intervention fixes the problem. It strengthens CytoDyn so immensely and destroys G's counter opposition completely. This would allow CytoDyn to pursue its pipeline at a much more rapid pace.

A bidding war and/or Governmental Intervention immediately and within seconds dramatically increases share price. It makes it nearly impossible for shorts to try to cover. Gone are all the problems associated with the determination of how the treatments for these indications develop, because the courting entity has the know how and is capable of getting it done on their own.

I suspect that the winner of this bidding war is a large Big Pharmaceutical who is bigger than G, who can set the direction, and who can set the record straight. I see CytoDyn being bought up and then licensed out. The buying company would own CytoDyn, but wouldn't want to Trial each and every indication, so it therefore chooses to license out only the indications which it doesn't want.

At the close of the bidding war, that time period provides many a shareholder an opportunity to exit. Because, CytoDyn would then be owned and operated by another massive entity, larger than G, who acquires the majority of indications, but also chooses to license a few different indications out. These are my thoughts. Hopefully, you agree that this makes some sense.

The timing looks good. Definitely rapidly approaching. By either bidding war or Governmental Intervention, I see the current back and forth situation of strike after strike dissipating rapidly and coming to an end swiftly, as in one full swoop, resulting in the elimination of CytoDyn's opposition and the subsequent provision of all those things necessary so as to advance and develop leronlimab at a pace suitable for its various applications against human infirmity.

I think I share this hope with many here, so, this is just to affirm the reason why we wait. I hope this was helpful.

Sunday post:

MGK_2

Game Changing
Loyal to Truth. This post was inspired by My69z.

Referencing this PR on July 9, 2024: CytoDyn Announces Amarex Settlement,

"The material terms of the settlement are as follows: (i) Amarex will pay $12,000,000 to CytoDyn, $10,000,000 was paid upon execution of the agreement and the remainder to be paid within the next 12 months; (ii) the surety bond, valued at $6,500,000, will be released to CytoDyn in full; (iii) all sums Amarex had claimed as due and payable, aggregating to approximately $14,000,000, will be eliminated, with no payment required from CytoDyn; and (iv) a mutual release of claims, resolving all legal claims between the parties."

Did we actually believe that CytoDyn only settled for just $12 million cash, the release of the $6.5 million surety bond and the elimination of all liability claims totaling $14 million to constitute the entirety of the settlement, when we knew full well that this was only a drop in the bucket of what the punitive and compensatory damages were actually worth? We all knew Amarex caused significant harm to CytoDyn and if justice got its way, was easily worth in excess of 10x this combined $32.5 million.

CytoDyn settled at this low figure, possibly because Amarex likely didn't have the more appropriate funds and their own insurance company also probably was tapped out and limited at $10 million. The $2 million probably came directly from Amarex, which is due by July 2025, together with the elimination of any liability claim and the release of the surety bond, is what was agreed to.

The claims against Amarex were severe and CytoDyn won the arbitration, so the judgement went in CytoDyn's direction. Even though the size of this settlement is paltry, it still represents a decimating blow to the loser. CytoDyn's case was very strong, and if they had the means to extract more, they would have. There just wasn't anything left on the table to take so as to justify an increase in the size of the settlement.

Truth was spoken that day, just not by the magnitude of the judgement. But CytoDyn seemed satisfied. Some expected CytoDyn to crumble under the sheer weight of the costs of litigation. But CytoDyn knew they were wronged and had the proof, and therefore, they proceeded with their claim.

From the most recent Press Release, CytoDyn Announces Promising Survival Observations In mTNBC, and since the entire PR pertains to this discussion, I'll repeat it here in its totality:

"VANCOUVER, Washington, Feb. 24, 2025 (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, today announced encouraging survival outcomes among a group of patients with metastatic triple-negative breast cancer (“mTNBC”) treated with leronlimab. Although mTNBC typically has a poor prognosis, observed survival rates at 12, 24, and 36 months after treatment with leronlimab compare favorably with reported life expectancy after treatment with currently approved therapies. 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."

With regard to mTNBC while discussing the Basket Trials, In the December 14, 2021 Conference Call, Nitya Ray spoke:

"27:60 Nitya Ray: The BTD application that is submitted is 28 patients from 3 different trials. And out of the 28, 6 had brain metastases. They are all mTNBC patients. So we have submitted all of the results, including all of the patients with brain metastases, now with the FDA and FDA is reviewing it and we are waiting for FDA to respond for BTD application and we expect to hear from them in about 2 weeks. 2-3 weeks. Our CTA application I believe was submitted on November 5. So by January 5, we should hear from FDA. and then we are going to discuss with FDA and see that forward with brain metastases. Now, these are not the only patients with brain metastases because these are mTNBC patients. But, we have other patients in the Basket Trial and not mTNBC, with brain metastases. And so we are very excited about what is happening with these patients. And so we are going to discuss this with the FDA and we do plan, after we receive the response from the FDA on the BTD application that is submitted, we are going to plan for perhaps another BTD just focusing on the brain metastases."

r/Livimmune - Game Changing
In expectation of the results of the mTNBC Clinical Trial, on September 5, 2022, I prepared the following: In Preparation For The Coming Results On mTNBC and wrote therein:

"Come 9/16/2022, we should be able to learn what the more refined PFS is for these 21 patients and what the more refined Overall Survivability is for these 21 patients. The study started 4/22/2019. By 7/19/21, the PFS was 8 months and the OS was 36 months. Since then, 13 months have passed. All in All, the patients were not very healthy. It was a combination of Compassionate Use, brain metastasis and patients had failed 2 other treatment protocols. Patients were treated differently, and may only have received up to 4 doses of leronlimab + carboplatin total while some other received much more, however, leronlimab may have been dosed even after PFS endpoint was reached and after the cancer had returned which may have extended OS. Hopefully, all of this is documented in the results of the trial. From the 7/19/21 PR, we currently had a PFS of 8 months and an OS of 36 months. Since November 2021, the PFS was recalculated to be 6.5 months and the OS became 12.5 months. 10 months have passed since then. Come 9/16/22, could the OS go to 20+ months?"

(How was CytoDyn able to put out in that PR a PFS of 8 months and an OS of 36 months if that period of time had not already passed? In short, they extrapolated.)

But the results of the mTNBC Clinical Trial were never released on the Estimated Study Completion of 9/16/2022. Why not? Knowing now what I didn't know then, I can say now that the data had to have been withheld. CytoDyn never said anything about why they didn't provide these crucial results, but that important data was due then, but it was never presented. Now, with the recent PR, it becomes clear that Amarex withheld the data, so CytoDyn had nothing with which to present. In fact, they had no presentation on 9/16/2022.

The settlement likely gave CytoDyn access to crucial clinical trial data which was previously unavailable to CytoDyn due to the dispute with Amarex. This is supported by the recent announcement of encouraging survival outcomes in metastatic triple-negative breast cancer (mTNBC) patients treated with leronlimab. Why would Amarex hide this data that was crucially important to all of humanity? In an effort to ruin CytoDyn's credibility? In an attempt to paint CytoDyn as duly incompetent? They no longer can claim that CytoDyn stopped payment, because they in fact lost the arbitration. Therefore, what is the truth here? Was there another reason they kept the information?

How much pressure was Amarex really under? Who were they in collusion with? Will this ever be uncovered and revealed? Could or Would the decision of the arbiter bring this information about? Yes, absolutely. What did Amarex need to do to avoid the decision of the arbiter? Settle.

Consider now the affected manuscripts. They probably do require tweaking. From the 12/14/2023 Webcast:

"00:33:19, Dr. Jacob Lalezari:

I've also recently reviewed the cancer data. And it is urgent that we get CD07 (mTNBC) published for that, again, provocative single benefit. So publications, are getting a protocol finalized, off hold, begin the process to implement, get these publications, including the NASH study, the long COVID study, submitted for peer review. I had talked to folks at NIH some years ago about our COVID data in the ICU population. They've been waiting to see the data in a peer reviewed format. And so that's a huge priority for me. And then at the same time, there's no reason why we cannot aggressively pursue partnerships to extend the research platform for leronlimab. And I will commit to that wherever that makes sense. So those are the significant events that, you know, I'll be looking for over the next, you know, two to six months."

r/Livimmune - Game Changing
From the 3/5/2024 Webcast:

"7:07: Turning now to the commitment to prioritize publications of our existing clinical data. I am pleased to announce that we are moving forward with the submission of (4) manuscripts in the coming weeks including (2) papers with 8 of 10 women with triple negative breast cancer. A paper in patients with multi-drug resistant HIV and a paper in patients with Mild to Moderate Covid-19.

7:40: The 1st publication will report on the observations that 8 of 10 women on the 3rd line therapies for triple negative breast cancer had either stable disease or a partial response after 6 months of combined treatment of leronlimab with a chemotherapy agent called carboplatin. This result compares favorably with historical controls.

8:09: The 2nd publication will report (2) further observations that suggests that leronlimab may have a role in the treatment of triple negative breast cancer. First, in the pooled analysis of 28 patients, there appeared to be a signal on the dose response. The patients on the higher 525mg dose of leronlimab, had a modestly increased progression free and overall survival compared to the 350mg dose.

Second, I think most provocatively, the pooled analysis showed that after receiving an initial dose of leronlimab, patients divided into one of two categories. About 25% of the patients had an increase in Circulating Tumor Cells, these are cells that are measured in the blood and can be referred to as CTCs. While about 75% of the patients had a decrease or absence of these CTCs in the weeks following the first dose of leronlimab.

9:17: That differentiation in CTC response in turn appeared to identify which patients subsequently responded to leronlimab with improved progression free and overall survival. Indeed, I believe the data on CTC response, is perhaps the most compelling part of the leronlimab story in triple negative breast cancer and could provide the basis for a screening test to identify which patients are most likely to respond from leronlimab in a follow up study.

I say all this to say, Why did Amarex keep data away from CytoDyn? Why was it part of the settlement to provide data to CytoDyn which had already been due them 3 years earlier? They claim they were withholding it because CytoDyn didn't pay, but since CytoDyn won the arbitration, their argument is null and void and that data rightfully belonged to CytoDyn all the while. Therefore, following the settlement, that data has been transferred to CytoDyn.

" 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."

The survival data for mTNBC patients is indeed remarkable. Some patients who had failed prior treatments for metastatic disease survived beyond 36 months, are currently alive, and show no evidence of active disease. This outcome is particularly significant given the aggressive nature of mTNBC and limited treatment options available.

Was there something behind that data they wanted to keep from CytoDyn? What did that data show? This is what I'm thinking. The fact that leronlimab eradicates metastatic disease to the brain? The fact that OS could not be definitively stated because patients were still alive? The fact that Circulating Tumor Cells essentially vanished after treatment with leronlimab?

What about the Basket Trial of various tumor types? Recall what Nitya Ray was saying. He wanted to gain BTD on metastatic Brain tumors. There were other tumors in that Basket Trial which could potentially reveal additional positive data. CytoDyn's access to the follow-up records of patients previously treated with leronlimab in oncology trials such as the Basket Trial could lead to even more discoveries across various cancer types

The mTNBC results I was looking for in September of 2022 should soon be revealed at ESMO in May of 2025. Shouldn't these all inclusive results also be incorporated in the (2) mTNBC manuscripts planned for publication as well?

Amarex agreed to provide this missing data which they sat on for years which they knew rightfully belonged to CytoDyn. But, they used the data similar to how hostages are used to negotiate with. As a means to augment the settlement agreement, which they knew fell far short of what it rightfully should have been, then they agreed to provide that data. But the value of this lost and forgotten data could become much more valuable than the one time payment. So that could be why CytoDyn agreed to the terms of the settlement agreement.

Certainly, this is not a fair resolution, but do CytoDyn shareholders have a choice? Not really. We hold and hope for the best. But, if what has been seen thus far holds true going forward, leronlimab becomes the treatment / cure for mTNBC plain and simple. 4 years of OS with no sign of ongoing disease = Cure.

At the time of settlement, they may not have realized that the return of the data which rightfully belonged to CytoDyn was worth far more than the $32.5 million in cash, eliminated liability and returned surety bond.

What else can we expect to come forth from this lost data? Actual OS of mTNBC patients to exceed even what was calculated through extrapolation? 36 months going on 48 months. Cure of mTNBC? The fact that leronlimab eradicates metastatic Brain tumors as Nitya Ray pointed out. How the addition of leronlimab augmented the beneficial effects of the chemotherapy carboplatin while attenuating its inflammatory side effects? Could the data show that there is a means by which we can know which patients respond to leronlimab and which patients will not? Abstract Changes In Circulating Tumor Cells

Is this why CytoDyn accepted the settlement agreement? Because the potential value of the data far exceeds the temporary monetary benefit? And why did Amarex agree to providing this data? Because they knew they could keep the monetary value of the settlement lower by providing the withheld (hostage) data and they didn't want this decision to go to the arbiter because they knew that if the decision was left to the arbiter, then their monetary payments would have put them into bankruptcy.

Why would Amarex withhold data on mTNBC? Life saving data, that could prolong the lives of patients suffering with the disease, and data that could cure patients of that disease? Why was it buried, left for dead? Would Amarex even have an answer? or would their finger be pointed at their Master? The arbiter would have been ruthless, CytoDyn remains cool and composed knowing that Truth is in its hands. CytoDyn has been in a war for so long, they knew the coming data would be well worth the compromised settlement. They knew the data had what it takes to get this mTNBC Clinical Trial back into ESMO, back in front of potential partners in the effort to cure this horrible disease.

This was a massive CytoDyn win against its own CRO parasite that shall be utilized to improve and preserve the lives of patients with mTNBC. CytoDyn finished those who directly attempted to play games with the truth, those who directly manipulated data to serve their own agenda, who attempted to silence them, by withholding their results. All of that has ended and their data shall be seen at ESMO in May. The first step to clearing sickness and disease is to eradicate the cause and that is what CytoDyn did in that settlement. It has cleared itself of its once CRO parasite which acted as a proxy of G.

CytoDyn has been on a Rampage ever since, clearing out its internal enemies and cleaning itself up for the work ahead which it is now in preparation and is undergoing. A Rampage that causes it to become the center of attention in that coming Bidding War. All of this means is that patience is required. That means, we are to live life. Have a really nice Sunday.

I don't see much discussion about Dr NP on here or anywhere else for that matter. Tom was providing a link. If people want to follow it that is up to them.

What is ironic is two of the posts since Tom posted the link are from YOU!

Thanks for posting. When is the sentencing?

Designer_Anteater_18

What if's answered by AI
If Cytodyn cures HIV, what big pharma companies would it negatively impact the most?

ChatGPT said:
If CytoDyn's leronlimab successfully cures or significantly improves HIV treatment, it would pose a major threat to several Big Pharma companies that dominate the HIV/AIDS market. The biggest losers would be:

1. Gilead Sciences (GILD) – HIV Market Leader
Gilead dominates the HIV treatment market, with blockbuster antiretroviral therapies (ARTs) like Biktarvy, Descovy, Truvada, and Genvoya.

Their HIV franchise brings in ~$17B+ annually, accounting for a huge portion of their revenue.

If leronlimab cures HIV or provides a superior treatment with fewer side effects, Gilead could lose billions in recurring revenue.

2. Viiv Healthcare (GSK, Pfizer, Shionogi Joint Venture)
Viiv, controlled by GlaxoSmithKline (GSK), owns Tivicay, Dovato, and Juluca—key integrase inhibitors for HIV.

They generate over $5B annually in HIV drug sales.

Leronlimab could disrupt GSK’s long-term HIV pipeline, forcing them to shift strategies or partner with CytoDyn.

3. Merck (MRK) – Integrase Inhibitors
Merck sells Isentress (raltegravir), one of the first integrase inhibitors used in HIV treatment.

While its HIV portfolio is smaller than Gilead’s or Viiv’s, a cure would make its existing therapies obsolete.

4. Johnson & Johnson (J&J) – Long-Acting HIV Drugs
J&J’s Janssen unit sells Cabenuva, a long-acting injectable for HIV treatment.

If leronlimab eliminates HIV, long-acting therapies like Cabenuva could become unnecessary, hitting J&J’s revenue stream.

5. AbbVie (ABBV) – HIV Drug Components
AbbVie produces Norvir (ritonavir), a key booster drug in many HIV regimens.

A cure would reduce demand for protease inhibitors, impacting sales of Norvir and related drugs.

Big Picture: Billions at Stake
A cure for HIV would eliminate the need for lifelong treatments, which is exactly how Big Pharma profits. The total HIV market is worth over $30 billion annually, and companies like Gilead, Viiv (GSK), and Merck heavily rely on recurring revenues from ARTs.

If CytoDyn succeeds, expect major resistance from these companies, including potential buyouts, smear campaigns, or regulatory hurdles. This is why a grassroots movement and retail investor backing (like the GameStop model) could be critical in countering Big Pharma’s influence and ensuring leronlimab reaches the market.

You said:
If Cytodyn cures mTNBC what big pharma companies would most negatively affected?

ChatGPT said:
If CytoDyn's leronlimab successfully cures or significantly improves treatment for metastatic triple-negative breast cancer (mTNBC), it would disrupt the oncology market, particularly hurting Big Pharma companies that rely on expensive, recurring cancer treatments. The biggest losers would be:

1. Gilead Sciences (GILD) – Trodelvy (mTNBC Blockbuster)
Gilead's Trodelvy (sacituzumab govitecan) is a key drug for mTNBC treatment, bringing in $1B+ annually, with expectations to surpass $5B in peak sales.

If leronlimab outperforms Trodelvy or works without severe side effects, Gilead’s mTNBC revenue could collapse.

Trodelvy is also expanding to other cancers, so a broader application of leronlimab could be even more damaging to Gilead.

2. Merck (MRK) – Keytruda (mTNBC & Other Cancers)
Keytruda (pembrolizumab) is Merck’s blockbuster immunotherapy, generating over $25B per year, with mTNBC as one of its key approved indications.

If leronlimab replaces Keytruda as a more effective, safer alternative, Merck would lose billions across multiple cancer types.

3. Roche (RHHBY) – Tecentriq (mTNBC Immunotherapy)
Tecentriq (atezolizumab) was previously approved for mTNBC but was withdrawn in the U.S. in 2021 due to disappointing results.

Roche still uses Tecentriq in other cancers, and if leronlimab succeeds, it could set a new oncology standard, reducing Roche’s immunotherapy sales.

4. Pfizer (PFE) & Seagen – Antibody-Drug Conjugates (ADCs)
Pfizer’s recent acquisition of Seagen for $43B was a massive bet on ADC cancer treatments, including for mTNBC.

If leronlimab proves superior, Pfizer’s investment in ADC-based breast cancer therapies could backfire, making Seagen’s portfolio less valuable.

5. AstraZeneca (AZN) – Enhertu & Imfinzi
Enhertu (trastuzumab deruxtecan), an ADC developed with Daiichi Sankyo, is expanding into breast cancers, including TNBC.

Imfinzi (durvalumab) is another immunotherapy that could be disrupted if leronlimab proves more effective.

AstraZeneca would lose market share if leronlimab becomes the preferred TNBC treatment.

Why This Matters: Cancer is a Cash Cow for Big Pharma
mTNBC is one of the deadliest and hardest-to-treat cancers, meaning current treatments are expensive, recurring, and highly profitable.

If leronlimab significantly outperforms existing therapies or even cures mTNBC, it could shatter the high-revenue cancer treatment model.

Big Pharma thrives on long-term cancer treatment regimens—a cure would be financially devastating for these companies.

The Big Pharma Playbook: Expect Resistance
If CytoDyn proves leronlimab works for mTNBC, expect Big Pharma to fight back:

Regulatory roadblocks (e.g., slow FDA approvals, added trial requirements)

Smear campaigns to question efficacy or safety

Stock manipulation (short-selling, misinformation)

Acquisition attempts (to shelve or control leronlimab’s release)

This is why a retail investor movement and grassroots campaign could be critical to ensuring leronlimab reaches patients.

You said:
Is there path to regulatory approval for any of leronlimab's indications, would it be possible to partner or license leronlimab for individual indications?

ChatGPT said:
Yes, there is a clear path to regulatory approval for leronlimab in multiple indications, and partnering or licensing leronlimab for individual indications is absolutely possible—and even likely.

1. Regulatory Path to Approval for Leronlimab
CytoDyn has already completed multiple clinical trials and has an open Investigational New Drug (IND) application with the FDA. The main regulatory hurdles involve completing the necessary Phase II/III trials and securing partnerships or funding to do so efficiently.

Current Status by Indication:
Cancer (Oncology) – mTNBC & CRC

CytoDyn received FDA clearance for a Phase II trial in metastatic colorectal cancer (mCRC), which is now being managed by Syneos Health (CRO).

mTNBC data from past trials showed strong survival benefits; if further studies confirm this, it could lead to FDA Breakthrough Therapy or Fast Track designation.

If a Big Pharma partner steps in (e.g., Merck, GSK, or Absci), approval could be expedited.

NASH (Non-Alcoholic Steatohepatitis)

The murine (mouse) study data showed that high-dose leronlimab outperformed Madrigal’s FDA-approved Resmetirom.

A partnership in NASH (potentially with Madrigal or Merck) could allow CytoDyn to skip early-phase trials and move directly to human clinical testing.

Given the huge market opportunity (NASH could be a $30B+ market), this is a prime target for partnership/licensing.

HIV

Leronlimab previously completed a Phase III trial for HIV and received FDA Refuse to File (RTF) due to CMC issues, not efficacy.

If CytoDyn resolves manufacturing concerns and secures a licensing or co-development deal (e.g., with Viiv, GSK, or a Gates Foundation-backed entity), HIV approval could be revived.

A conditional approval or Fast Track designation could be possible for special populations (e.g., multi-drug-resistant HIV patients).

COVID-19 & Long COVID

Past trials showed efficacy in COVID-19 (especially in severe cases), but due to the shifting regulatory landscape, this indication is on hold.

However, Long COVID is still an open opportunity, and new studies could be launched under an Emergency Use Authorization (EUA) pathway if a new outbreak or strong data emerges.

2. Can CytoDyn License or Partner Leronlimab by Indication?
Yes, it is entirely possible to license or partner leronlimab for individual indications—and this is likely the best strategy for CytoDyn given its financial constraints.

Why Licensing Partnerships Make Sense:
Big Pharma prefers targeted, single-indication deals rather than acquiring an entire company.

CytoDyn lacks cash flow, so partnering allows them to get upfront cash and milestone payments without dilution.

Multiple partnerships could exist simultaneously, e.g.:

A cancer partnership (e.g., with Merck for mTNBC/CRC)

A NASH partnership (e.g., with Madrigal or GSK)

An HIV licensing deal (e.g., with Viiv/GSK or a Gates Foundation-backed initiative)

Potential Partner Scenarios:
Indication Potential Partners
mTNBC & CRC Merck, Gilead, Pfizer, AstraZeneca, Roche
NASH Madrigal, Merck, Novo Nordisk, GSK
HIV Viiv Healthcare (GSK/Pfizer), Merck, Gilead, Gates Foundation-backed orgs
Long COVID NIH, Government Grants, Big Pharma with interest in immune modulation
Conclusion: Path Forward
Regulatory approval is achievable—especially in oncology and NASH, where CytoDyn is already advancing.

Leronlimab could be licensed per indication, allowing CytoDyn to retain ownership while leveraging Big Pharma’s resources.

The biggest challenge is securing funding or partnerships—but the right deal could unlock billions in value.

If a grassroots movement and retail investor backing can raise awareness, it might force Big Pharma’s hand to accelerate partnerships or pursue acquisitions.