theswordman
3 days ago
Its possible that person does not know/understand --For the avoidance of doubt, Chicago Venture Partners (“CVP”) currently holds two notes with Borrower
– one in the name of Uptown Capital, LLC and another in the name of Streeterville Capital, LLC – and the
Monthly Payment Amount will accrue and be applicable to one of the two notes on a monthly basis. CVP may,
at its discretion, choose which of the two notes it would like to apply the Monthly Payment Amount to on a
month-by-month basis..
BUT you would "think" they could grasp --on some level--
LENDER: Streeterville Capital, LLC
By: /s/ John M. Fife
John M. Fife, President
BORROWER: CytoDyn, Inc.
By: /s/ Mitch Cohen
Name: Mitch Cohen
Title: Interim CFO
LENDER: Uptown Capital, LLC
By: /s/ John M. Fife
John M. Fife, President
BORROWER: CytoDyn, Inc.
By: /s/ Mitch Cohen
Name: Mitch Cohen
Title: Interim CFO
But NEVER let FACT get in the way of opinion
kgromax
4 days ago
And the latest 10Q filing by the company proves again that I was correct, and that you were wrong - Fife is bleeding dry this dead horse:
Extension(s) to April 2, 2021 and April 23, 2021 Notes
In April 2025, the Company and the holders of convertible notes issued by the Company on April 2, 2021 and April 23, 2021 (the
“Noteholders”) agreed to extend the maturity date of each of the notes by one year (the ”Extension Period”). The Company agreed to a total
monthly payment of $750,000 covering both notes until the extended maturity date. During the Extension Period, the Company will issue
shares of common stock equal in value to the $750,000 monthly payment calculated based on the lower of (i) the previous trading day’s
closing price, or (ii) the average of the five previous trading day closing prices. The interest rate for each note was also lowered to 6% as
part of the extension.
https://www.cytodyn.com/investors/sec-filings/all-sec-filings/content/0001558370-25-004774/0001558370-25-004774.pdf
Monroe1
4 days ago
With Young Adult Cancer on the Rise, New Therapies Spark Investor Buzz
PR Newswire - 10:15 AM ET 4/14/2025 Investment News
VANCOUVER, BC, April 14, 2025 /PRNewswire/ -- Equity Insider News Commentary – Routine medical appointments or cancer screenings—critical for catching the disease in earlier, more treatable stages—has dropped to just over 50% of the population. At the same time, doctors are raising alarm bells over a noticeable increase in cancer diagnoses among younger adults, especially women. With proposed funding cuts to the NIH now on the table and new estimates suggesting that drug tariffs could add $10,000 or more to treatment costs, the path forward may rely less on government programs and more on private-sector breakthroughs
Remember our CEO and others have mentioned... we are really an oncology company. Following the European Conference in a few weeks, a significant notoriety among European and elsewhere will occur in the recognition of leronlimab. More attention and European Pharma competition won't hurt at all.
This is our year. $$$2025$$$
Blueheel1
5 days ago
docj - thanks for your great work on the board. You are providing relevant information, and playing an important role.
I've been off the board for quite awhile, and even missed the March letter as I've been busy with other things. But I thought the letter was powerful. My key take-aways:
1. We have sufficient cash. This is the real key at this point, given the darker tone of the markets - fundraising for pre-revenue biotechs will only get tougher.
2. We have found the critical path in terms of indications. (TNBC snd CLC, the 2 highest potential return indications). Much of my concerns over time have been the scatter-gun approach to chasing too many indications. Jay and the team seem to have found the critical path - and Pestell is highly respected in this field.
3. The mention of partnerships in the near term. For the first time, i feel we likely have material discussions at a stage where they could result in a partnership this year. If it's a well respected company, this would be huge.
To be clear, we still have to execute, and I think the risks (especially given the market backdrop) remain high. But I personally are more excited about the near / intermediate term for this investment than I have been in a long time.
docj
5 days ago
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.
docj
1 week ago
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.”
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FooBarAndGrill
4 days ago
fung_derf
5 days ago
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