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Journal Pre-Print Describes How CytoDyn’s Leronlimab Disrupts CCL5/RANTES-CCR5 Pathway, Thereby Restoring Immune Homeostasis, Reducing Plasma Viral Load, & Reversing Hyper-Immune Activation and Inflammation in Critical COVID-19 Patients

On May 5,2020, CytoDyn Inc. (OTC.QB: CYDY), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5-antagonist with the potential for multiple therapeutic indications, announced that a pre-print version of the manuscript has been made publicly available on posting on the Research Square and MedRxiv portals. The pre-print will soon be finalized and published in a prestigious journal. The pre-prom describes the immunological mechanism by which CytoDyn’s HIV drug leronlimab restores immune function and impacts disease in COVID-19 patients. Consistent with CytoDyn’s commitment to disseminate results to inform the public health response to SARS-CoV-2, the manuscript has been made publicly available as a pre-print prior to final journal publication, which should occur shortly. The manuscript is entitled: “Disruption of the CCL5/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma Viral Load in Critical COVID-19.” The pre-print full manuscript can be accessed at: (https://www.researchsquare.com/article/rs-26517/v1) and (https://www.medrxiv.org/content/10.1101/2020.05.02.20084673v1). The manuscript has been submitted for publication and is currently under peer review. The pre-print manuscript has also been shared with the World Health Organization (WHO). As described in the pre-print, in a cohort of ten critically ill patients, after treatment with leronlimab, these critically ill patients experienced reversed hyper immune activation and inflammation, as well as reversed immunosuppression, thereby facilitating a more effective immune response correlated with decreases in SARS-CoV-2 virus levels in blood.

Pfizer & BioNTech Launch Global COVID-19 mRNA Vaccine Development Program

On March 5, 2020, Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) announced that the first participants have been dosed in the U.S. in the Phase 1/2 clinical trial for the BNT162 vaccine program to prevent COVID-19. The trial is part of a global development program, and the dosing of the first cohort in Germany was completed last week. The Phase 1/2 study is designed to determine the safety, immunogenicity, and optimal dose level of four mRNA vaccine candidates evaluated in a single, continuous study. The dose level escalation portion (Stage 1) of the Phase 1/2 trial in the U.S. will enroll up to 360 healthy subjects into two age cohorts (18-55 and 65-85 years of age). The first subjects immunized in Stage 1 of the study will be healthy adults 18-55 years of age. Older adults will only be immunized with a given dose level of a vaccine candidate once testing of that candidate and dose level in younger adults has provided initial evidence of safety and immunogenicity. Sites currently dosing participants include New York University (NYU) Grossman School of Medicine and the University of Maryland School of Medicine, with the University of Rochester Medical Center/Rochester Regional Health, and Cincinnati Children’s Hospital Medical Center to begin enrollment shortly. “With our unique and robust clinical study program underway, starting in Europe and now the U.S., we look forward to advancing quickly and collaboratively with our partners at BioNTech and regulatory authorities to bring a safe and efficacious vaccine to the patients who need it most.

Supercomputer Simulations Present Potential Active Substances Against Corona Virus; 42,000 Compounds Surveyed; Four Existing Hepatitis C Drugs Bind Very Strongly to SARS-CoV-2 (COVID-19)

Several drugs already approved for treating hepatitis C viral infection were identified as potential candidates against COVID-19, a new disease caused by the SARS-CoV-2 coronavirus. This is the result of research based on extensive calculations using the MOGON II supercomputer at Johannes Gutenberg University Mainz (JGU) in Germany. One of the most powerful computers in the world, MOGON II is operated by JGU and the Helmholtz Institute Mainz. As the JGU researchers explained in their paper recently published at the World Health Organization (WHO) website (https://www.who.int/bulletin/online_first/COVID-19/en/), they had simulated the way that about 42,000 different substances listed in open databases bind to certain proteins of SARS-CoV-2 and thereby inhibit the penetration of the virus into the human body or its multiplication. "This computer simulation method is known as molecular docking and it has been recognized and used for years. It is much faster and less expensive than lab experiments," said Professor Thomas Efferth of the JGU Institute of Pharmacy and Biomedical Sciences, lead author of the study. "As far as we know, we were the first to have used molecular docking with SARS-CoV-2. And it is fantastic news that we have found a number of approved hepatitis C drugs as promising candidates for treatment." Using the MOGON II supercomputer, the researchers made more than 30 billion single calculations within two months and found that compounds from the four hepatitis C drugs simeprevir, paritaprevir, grazoprevir, and velpatasvir have a high affinity to bind SARS-CoV-2 very strongly and may therefore be able to prevent infection. "This is also supported by the fact that both SARS-CoV-2 and the hepatitis C virus are a virus of the same type, a so-called single-stranded RNA virus," explained Professor Efferth.

Recently Recovered COVID-19 Patients Produce Varying Virus-Specific Antibodies & T-Cells

Most newly discharged patients, who recently recovered from COVID-19, produce virus-specific antibodies and T-cells, suggests a study published online on May 3, 2020 in Immunity, but the responses of different patients are not all the same. The article is titled "Detection Of SARS-Cov-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals." While the 14 patients examined in the study showed wide-ranging immune responses, results from the 6 of them who were assessed at two weeks after discharge suggest that antibodies were maintained for at least that long. Additional results from the study indicate which parts of the virus are most effective at triggering these immune responses and should therefore be targeted by potential vaccines. It is not clear why immune responses varied widely across the patients. The authors say this variability may be related to the initial quantities of virus that the patients encountered, their physical states, or their microbiota. Other open questions include whether these immune responses protect against COVID-19 upon re-exposure to SARS-CoV-2, as well as which types of T-cells are activated by infection with the virus. It is also important to note that the laboratory tests that are used to detect antibodies to SARS-CoV-2 in humans still need further validation to determine their accuracy and reliability. "These findings suggest both B- and T-cells participate in immune-mediated protection against the viral infection," says co-senior study author Chen Dong, PhD, of Tsinghua University in Beijing, China. "Our work has provided a basis for further analysis of protective immunity and for understanding the mechanism underlying the development of COVID-19, especially in severe cases. It also has implications for designing an effective vaccine to protect against infection."

NIH Launches Public-Private Partnership to Speed COVID-19 Vaccine & Treatment Options; Health Agencies & Leading Pharmaceutical Companies Join Forces to Accelerate Pandemic Response

According to an April 17, 2020 press release, the National Institutes of Health (NIH) and the Foundation for the NIH (FNIH) are bringing together more than a dozen leading biopharmaceutical companies, the Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response, the Centers for Disease Control and Prevention (CDC), the U.S. Food and Drug Administration (FDA), and the European Medicines Agency to develop an international strategy for a coordinated research response to the COVID-19 pandemic. The planned “Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)” partnership will develop a collaborative framework for prioritizing vaccine and drug candidates, streamlining clinical trials, coordinating regulatory processes, and/or leveraging assets among all partners to rapidly respond to the COVID-19 and future pandemics. This is part of the whole-of-government, whole-of-America response that the Administration has led to beat COVID-19. “We need to bring the full power of the biomedical research enterprise to bear on this crisis,” said NIH Director Francis S. Collins (photo), MD, PhD. “Now is the time to come together with unassailable objectivity to swiftly advance the development of the most promising vaccine and therapeutic candidates that can help end the COVID-19 global pandemic.” Coordinated by the FNIH, ACTIV government and industry partners will provide infrastructure, subject matter expertise and/or funding (both new and in-kind) to identify, prioritize, and facilitate the entry of some of the most promising candidates into clinical trials.

CytoDyn Provides Comprehensive Update on Leronlimab Drug for COVID-19; Drug Calms “Cytokine Storms,” Restores Immunologic Homeostasis, Reduces Plasma Viral Load; Early Results Suggest Clear Superiority Over Gilead’s Remdesivir; Clinical Trials Described


--Leronlimab Is “Triple Threat” Drug for COVID-19
--Leronlimab Quiets “Cytokine Storms," Restores Immunologic Homeostasis, & Decreases Viral Load
--Gilead’s Anti-Viral Remdesivir & Genetech’s Anti-IL-6 Actemra Called “Piecemeal Approaches to Highly Complex Patholgenesis”
--Leronlimab Approach Has Wide General Application to All Facets of COVID-19 Infection, Including All Related Co-Morbidities, Including Renal Failure, Liver Failure, & Clotting Issues
--Broad Approach of Leronlimab Is Analogized with PDL-1 & Broad Non-Specific Approach of Checkpoint Inhibitor Blockade in Cancer (2018 Nobel Prize)
--Leronlimab Predicted to Also Have Effectiveness Against Other Viruses, and Also Against Currently Unknown Viruses That Might Become Future Emerging Threats
--RANTES (Master Immunomodulator Molecule) Drives COVID-19 Pathogenesis
--RANTES Levels Are 100X Normal in Critically Ill COVID-19 Patients
--RANTES Binds to CCR5 Receptor on Immune Cells, Launching Vicious Cycle of Immune Cell Recruitment (T-Cells & Macrophages), Local Release of Cytokines and More RANTES, Influx of More Immune Cells, Release of More Cytokines and More RAANTES, and On & On
--Body Becomes Literally "On Fire" with Inflammation Causing Mass Multi-Organ System Issues That Can Be Blocked by Leronlimab
--Leronlimab Blocks CCR5 Cell-Surface Receptor for Chemokines & Prevents RANTES Binding
--Leronlimab Administered in Two Weekly Doses Via Subcutaneous Injection
--Gilead’s Remdesivir Is Adminstered Daily in Hour-Long IV Injections
--CytoDyn Scientist Argues That Leronlimab Will Be Highly Effective on Its Own, No Need for Combination with Remdesivir
--CytoDyn Scientist Sounds Warning on Blood Supply As He Has Found, for the First Time, That COVID-19 Virus Is Present in the Plasma of Patients

FDA Approves 54 Emergency INDs for Leronlimab Treatment of Corona Virus; CytoDyn Requests Compassionate Use from FDA for COVID-19 Patients Not Eligible for Participation in Two Ongoing Clinical Trials in U.S.

On May 4, 2020, CytoDyn Inc. (OTC.QB: CYDY), (“CytoDyn” or the “Company"), a late-stage, Vancouver, Washington-based biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced that the Company is expecting enrollment completion for its 75 patient, Phase 2 double-blinded, placebo-controlled, randomized study by the end of this month. CytoDyn has submitted a request to the FDA to grant expanded access, also known as “compassionate use,” to make leronlimab available for patients not eligible for participation in two ongoing clinical trials for coronavirus infections. Many severe and critically-ill patients, who have received off-label immunomodulatory treatments for COVID-19, are excluded from participation in the Company’s Phase 2b/3 clinical trial and could potentially benefit from access to leronlimab under a compassionate use program. There are 49 COVID-19 patients who have enrolled for treatment with leronlimab through emergency INDs (eINDs). Four out of 11 critically ill patients with a multitude of pre-existing conditions survived after treatment, and of the next 38 patients, many were extubated, improved, or were discharged. Nader Pourhassan, PhD, Director, President, and Chief Executive Officer of CytoDyn, said, “We are very excited about the continuing positive responses from eIND patients following their treatment with leronlimab. We are equally excited about the prospects for patients should the FDA grant access to leronlimab under the compassionate use program. During this past Saturday, we had to overcome many obstacles for two patients who desperately wanted leronlimab. One patient was in the same hospita (Montefiore Medical Center in New York City) that enrolled the first 11 patients and the second was a well-known patient in Los Angeles.

Mini-Antibodies (Nanobodies) from Llamas Could Be Big Factor in Fight Against COVID-19; Unusually Tiny Antibodies Can Be Administered from Inhaler and Get Quickly & Directly to the Site of Infection in the Lungs

The hunt for an effective treatment for COVID-19 has led one team of researchers to find an improbable ally for their work: a llama named Winter (photo). The team -- from The University of Texas at Austin, the National Institutes of Health, and Ghent University in Belgium -- reports their findings about a potential avenue for a coronavirus treatment involving llamas in an article to be published online on May 5, 2020 in Cell. The paper is currently available online as a "pre-proof," meaning it is peer-reviewed but undergoing final formatting. The pre-print was posted in the bioRxiv portal on March 28, 2020. The current title of the article is “Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies.” The researchers linked two copies of a special kind of antibody produced by llamas to create a new antibody that binds tightly to a key protein on the coronavirus that causes COVID-19. This protein, called the spike protein, allows the virus to break into host cells. Initial tests indicate that the antibody blocks viruses that display this spike protein from infecting cells in culture. "This is one of the first antibodies known to neutralize SARS-CoV-2," said Jason McLellan, PhD, Associate Professor of Molecular Biosciences at UT Austin and co-senior author, referring to the virus that causes COVID-19. The team is now preparing to conduct preclinical studies in animals such as hamsters or nonhuman primates, with the hopes of next testing in humans. The goal is to develop a treatment that would help people soon after infection with the virus. "Vaccines have to be given a month or two before infection to provide protection," Dr. McLellan said. "With antibody therapies, you're directly giving somebody the protective antibodies and so, immediately after treatment, they should be protected.

Researchers Identify Binding Model of Congo Red Dye to Amyloid Fibrils; Finding May Aid Development of Strategies for Inhibiting Amyloid Formation in Amyloid-Origin Diseases Such As Alzheimer’s & Parkinson’s

The aggregation of proteins in amyloid structures, a process described in mammals and fungus and bacteria, is implied in approximately 36 human diseases, including Alzheimer’s disease, Parkinson’s disease and type 2 diabetes. Most of the amyloid fibers are known for their ability to bind Congo Red (https://en.wikipedia.org/wiki/Congo_red), regarded as a specific marker of amyloid structures. This adds a great value to the compound Congo-Red, because it is one of the most used to detect the presence of amyloids and characterize the process of aggregation involved in amyloidogenic diseases. In a paper published online on February 19, 2020 in the journal Angewandte Chemistry International Edition, researchers at the University of Barcelona, and colleagues, identified the binding model of this dye. Specifically, the study focused on the interaction of Congo Red in amyloid structures formed by the HET-s (heterokaryon incompatibility protein s) prion particle (https://www.pnas.org/content/111/14/5201). The article is titled is titled ““On the binding of Congo Red to amyloid fibrils.” From a technological perspective, the results provide the molecular basis to explain the spectral changes in Congo Red when it joins amyloid fibers, which enables them to exploit this process in the study of aggregation of other proteins. Most important, is the fact that knowing this mechanism could enable researchers to identify potential strategies of inhibition of amyloid fibers involved in amyloid-origin diseases.

Exosome Company Codiak BioSciences Will Present New Preclinical Data in Multiple Presentations at American Society of Gene and Cell Therapy (ASGCT) Annual Meeting to Be Held Virtually May 12-15, 2020

On April 30, 2020, Codiak BioSciences, Inc., a company at the forefront of advancing engineered exosomes as a new class of biologic medicines, announced that six preclinical data presentations on its engEx™ Platform programs, of which three are oral presentations, will be presented at the 23nd Annual Meeting of The American Society of Gene and Cell Therapy (ASGCT), which will be held virtually on May 12-15, 2020. In addition, Codiak’s Executive Vice President of Manufacturing and Process Sciences, Konstantin Konstantinov, PhD, will give an invited lecture on Codiak’s approach to industrial exosome manufacturing as part of the scientific symposium entitled “Advancing Therapeutic Exosomes for the Treatment of Disease,” which is being organized by the Nanoagents & Synthetic Formulations Committee. “These data presentations highlight the significant progress that we have made on our engEx Platform and its broad potential to generate new classes of molecular medicines,” said Jonathan Finn, PhD, Vice President, Discovery Research at Codiak BioSciences. “Targeted delivery is critical for drug development, and we are particularly encouraged by our data showing that we can use our engEx platform to selectively drive exosome uptake into multiple cell types both in vitro and in vivo. We are also excited to debut our data using exosomes as a novel vaccine approach, capitalizing on the unique immune response our exoVACC™ platform can generate when compared with standard vaccine platforms.” The titles and schedules for the Codiak presentations at the ASGCT annual meeting are listed below.

CODIAK ORAL PRESENTATIONS

“Induction of Potent Systemic and Tissue Resident Immune Responses by exoVACC™: a Novel Exosome-based Vaccine Platform”
Abstract number: 66
Date/Time: Tuesday May 12, 2020, at 10:45 AM ET

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