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Vyrologix (Leronlimab) Antibody

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December 4, 2021
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Vyrologix Leronlimab Description

CytoDyn's Vyrologix™ Leronlimab (PRO 140) is a CCR5 antagonist with the potential for multiple therapeutic indications. It belongs to a new class of therapeutics - CCR5 Antagonist - that protects healthy cells from viral infection.

Vyrologix is a humanized monoclonal antibody targeted against the CCR5 receptor found on T lymphocytes of the human immune system. The CCR5 receptor plays a central role in modulating immune cell trafficking to sites of inflammation.

Vyrologix - Leronlimab, among various potential applications, is a viral-entry inhibitor in HIV/AIDS. It binds to CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab does not work on other strains of HIV (for example, X4); however, R5 is the most dominant strain of HIV. 

Only two documented cases of HIV cure have been reported, the Berlin and London patients, who both were cured via allogeneic stem cell transplants from CCR5-deficient donors. However, in pre-clinical studies, Leronlimab has demonstrated the ability to mimic CCR5 deficiency by binding to CCR5 receptors, thereby preventing HIV from interacting with its primary co-receptor. 

CytoDyn has identified the CCR5 receptor as a target in HIV, GVHD, NASH, cancer metastasis, transplantation medicine, multiple sclerosis, traumatic brain injury, stroke recovery, and various inflammatory conditions. Due to Vyrologix - Leronlimab selectivity and target-specific mechanism of action, this monoclonal antibody allows chemokine binding (CCL3, CCL4) at therapeutic doses and does not activate the immune function of the receptor. 

In July 2021, CytoDyn announced that it had submitted a dose justification report to the U.S. FDA, an integral step in the resubmission process for its BLA, expected to complete by the end of the first quarter of calendar 2022. 

On November 19, 2021, Fronters in Immunology published the results of an Original Research study that found: Establish two CCR5 receptor occupancy calculation methods for longitudinal monitoring of anti-CCR5 therapeutic antibody blockade efficacy in both macaques and humans; Demonstrate that CCR5+CD4+ T cell levels temporarily increase with leronlimab treatment; and; Facilitate future detailed investigations into the immunological impacts of CCR5 inhibition in multiple pathophysiological processes. Additionally, these researchers stated: The CCR5 RO assays described here will be an important study measurement for any CCR5 antibody-based agent, and can be modified for any antibody-based agents that have a clearly defined cell surface protein target. In the case of the anti-CCR5 antibody Leronlimab, the ability to accurately measure CCR5 RO will advance both pre-clinical and clinical studies, furthering our understanding of the immunological impacts of CCR5 for multiple pathophysiologic processes.

The U.S. FDA has designated Leronlimab (Pro 140) for Fast Track Approval to treat HIV and metastatic cancer. It binds to CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab does not work on other strains of HIV (for example, X4); however, R5 is the most dominant strain of HIV.

Molecular Formula: C6534 H10036 N1720 O2040 S42. U.S. NIH Chemical Name: Immunoglobulin G4, anti-(human Chemokine receptor CCR5) (humanized monoclonal PRO 140 γ4-chain), disulfide with humanized monoclonal PRO 140 κ-chain, dimer

Vancouver, Washington-based CytoDyn (OTCQB: CYDY) is a late-stage biotechnology company developing innovative treatments for multiple therapeutic indications using leronlimab, a novel humanized monoclonal antibody targeting the CCR5 receptor. CCR5 plays a critical role in the ability of HIV to enter and infect healthy T-cells. In addition, it appears to be implicated in tumor metastasis and immune-mediated illnesses, such as NASH.

Vyrologix Leronlimab Indications - COVID-19

The Vyrologix Leronlimab (Pro 140) is in early clinical trials to treat COVID-19 disease. Leronlimab is intended to serve as a therapy for patients who experience respiratory illness due to contracting COVID-19. However, these patients' treatment was not under the Company's proposed randomized, Phase 2 clinical trial protocol recently submitted to the FDA. On May 5, 2021, the FDA stated 'With the conclusion of both the CD10 and CD12 clinical trials, it has become clear that the data currently available do not support the clinical benefit of leronlimab for the treatment of COVID-19.'

The Philippines FDA granted Compassionate Special Permits for Leronlimab as requested by medical specialists for the treatment of COVID-19 patients.

The "cytokine storm" is believed to play an integral role in developing acute respiratory distress syndrome (ARDS) in those affected by COVID-19. Chemokines and chemokine receptors play a critical role in the recruitment, activation, and coordination of leukocytes in lung inflammation's pathophysiology. The ARDS of COVID-19 results from the accumulation of neutrophils within the pulmonary circulation and alveolar spaces.

Leronlimab Indication for HIV

Leronlimab is a viral-entry inhibitor in HIV/AIDS. Research may prove that leronlimab is a safe and effective option for treating people with R5-tropic virus (a strain of HIV), including those for whom other entry and fusion inhibitors, such as maraviroc (brand name: Selzentry), are not working. In the setting of HIV/AIDS, leronlimab is a viral-entry inhibitor; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab has been the subject of nine clinical trials, each of which demonstrated that leronlimab could significantly reduce or control HIV viral load in humans.

On December 1, 2021, CytoDyn announced it had completed the submission of all the major sections of CMC modules, a critical part of the U.S. FDA Biologics License Application for HIV. This submission was made under rolling review consistent with guidance from the FDA. Only the clinical section remains to be submitted.

Leronlimab Indication for Liver Fibrosis

CytoDyn is also conducting a Phase 2 clinical trial for NASH to evaluate the effect of leronlimab on liver steatosis and fibrosis. Pre-clinical studies revealed a significant reduction in NAFLD and a reduction in liver fibrosis using leronlimab. There are currently no FDA-approved treatments for NASH, which is a leading cause of liver transplants.

Leronlimab Use Against Triple-Negative Breast Cancer

CytoDyn Inc. announced on November 8, 2021, it had submitted to the U.S. FDA an application for Breakthrough Therapy designation for leronlimab as a potential treatment for mTNBC. Previously, the FDA granted CytoDyn Fast Track designation to explore potential indications using leronlimab to treat metastatic cancer

Health Canada authorized the emergency use of leronlimab on November 16, 2021, for the treatment of a patient with metastatic triple-negative breast cancer.

Vyrologix Leronlimab Side Effects

Tell your health care provider promptly about any unusual or severe symptoms that develop after you receive this vaccine or directly to Vaccine Adverse Event Reporting System (VAERS). The VAERS toll-free number is 1-800-822-7967, or report online to www.vaers.hhs.gov.

CytoDyn, Inc. Finacial News (OTCQB: CYDY)

October 28, 2021 - CytoDyn Inc. announced the Annual Meeting will be held virtually on November 24, 2021, at 8:00 a.m. Pacific Time. The adjournment provides the Company with additional time to solicit proxies from its shareholders to achieve a quorum at the Annual Meeting.

May 31, 2021 - Form 10-k for the fiscal year ended May 31, 2021.

Vyrologix Leronlimab News

November 24, 2021 - CytoDyn Inc. reported data from its trial treating NASH (nonalcoholic steatohepatitis). Leronlimab open-label NASH results continue to show reductions in fat and fibrosis suggestive of a potential therapy not only for NAFLD (Non-Alcoholic Fatty Liver Deposit) but also in NASH. Fat reductions by proton density fat fraction PDFF up to 45% along with reductions in fibrosis up to 8% by CT1 were noted from baseline after just 14 weeks of treatment. The reductions in fibrosis were seen in both severe and mild-moderate NASH cases.

November 19, 2021 - CytoDyn Inc. announced that its research paper entitled “CCR5 receptor occupancy analysis reveals increased peripheral blood CCR5+CD4+ T cells following treatment with the anti-CCR5 antibody Leronlimab” has been accepted by Frontiers in Immunology. Collectively, these results establish two RO calculation methods for longitudinal monitoring of anti-CCR5 therapeutic antibody blockade efficacy in both macaques and humans, demonstrating that CCR5+CD4+ T cell levels temporarily increase with Leronlimab treatment, and facilitate future detailed investigations into the immunological impacts of CCR5 inhibition in multiple pathophysiological processes.

November 8, 2021 - We are grateful to have already received Fast Track designation for leronlimab for this indication (mTNBC) and congratulate Dr. Nitya Ray and his team for preparing the data analysis needed to file this BTD application so quickly," commented Nader Pourhassan, Ph.D.

November 3, 2021 - CytoDyn Inc. announced preliminary results from the first five patients treated with leronlimab in its Phase 2 trial for NASH (nonalcoholic steatohepatitis) open-label. These preliminary findings suggested fatty deposits were lowered on all 5 patients by as much as 45%, as compared to the baseline measurement. In addition, fibrosis was also lowered by as much as 10%, in 4 out of 5 patients as compared to the baseline measurement. The Phase 2 trial for 90 patients is designed to test whether leronlimab may inhibit the devastating liver fibrosis associated with NASH.

November 3, 2021 - CytoDyn Inc. announced updated results from its current cancer study using leronlimab (in varying doses) to treat 28 patients with CCR5+ Metastatic Triple-Negative Breast Cancer (“mTNBC”), who had failed at least two lines of previous therapy. This ongoing updated analysis is from 28 pooled patients, 16 from our Compassionate Use Study, 10 from the Phase 1b/2 Study, and 2 from the Basket Study.

October 27, 2021 - CytoDyn Inc. announced today the U.S. FDA had accepted the revised “Rolling Review” timeline for the Company’s upcoming resubmission of its Biologics License Application (“BLA”) for leronlimab as a combination therapy for highly treatment-experienced HIV patients. The Company also announced that it expects the non-clinical and CMC sections of the BLA to be resubmitted to the FDA in November 2021, and, as previously disclosed, the clinical section of the BLA is anticipated to be completed and resubmitted during early 2022.

October 25, 2021 - CytoDyn Inc. announced the treatment of the first patient in its pivotal Phase 3 trial (CD16) in Brazil for critically ill COVID-19 patients. An interim analysis will be conducted 28 days following the enrollment of 127 patients.

October 7, 2021 - CytoDyn Inc. announced a study treating triple-negative breast cancer (TNBC) with leronlimab in a humanized TNBC xenograft model. The study is intended to determine the potential synergistic therapeutic efficacy of leronlimab in combination with immune checkpoint blockade (ICB) to attempt to raise the standard of care for breast cancer patients. This investigator-initiated study is led by Jangsoon Lee, Ph.D., assistant professor of Breast Medical Oncology Research at The University of Texas MD Anderson Cancer Center.

September 22, 2021 - CytoDyn Inc. announced that Brazil's regulatory authority, Agência Nacional de Vigilância Sanitária, has approved the start of a different Phase 3 CD16 clinical trial of leronlimab. The new clinical trial will focus on hospitalized COVID-19 patients in critical condition who require mechanical and invasive ventilation or Extracorporeal Membrane Oxygenation.

September 13, 2021 - CytoDyn Inc. (OTCQB: CYDY) announced Nader Pourhassan, Ph.D., President and CEO, and Scott Kelly, M.D., Chairman, and Chief Medical Officer, will provide a comprehensive business update at the upcoming Emerging Growth Conference. Previous investor presentations are available at this link.

September 9, 2021 - CytoDyn Inc. announced the treatment of the first patient in its pivotal Phase 3 COVID-19 trial in Brazil for patients with severe symptoms. An interim analysis will be conducted 28 days following the enrollment of 245 patients, 40% of the total number of patients enrolled in the trial.

August 26, 2021 - CytoDyn Inc. (OTCQB: CYDY) announced today Seenu Srinivasan, Ph.D., as Executive Director-CMC Regulatory Affairs.

August 25, 2021 - CytoDyn reveals data from its final mTNBC report with its flagship drug, leronlimab, in a video interview.

August 3, 2021 - CytoDyn Inc. announced that Brazil's regulatory authority Agência Nacional de Vigilância Sanitária)has approved the previously submitted clinical trial protocol to commence patient enrollment in its CD17 trial for severe COVID-19 patients. As a result, the Academic Research Organization Albert Einstein Israelite Hospital in Brazil will conduct the trial.

July 19, 2021 - CytoDyn Inc. announced 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.

May 19, 2021 - According to Pharmaceutical Technology, CytoDyn is set to submit the results from the Phase III CD12 clinical trial of Vyrologix (leronlimab-PRO 140), seeking potential regulatory approval for the drug to treat severe to critically ill patients with Covid-19.

May 3, 2021 - CytoDyn, a late-stage biotechnology company developing leronlimab (Vyrologix™ or PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced a comprehensive update three continuing extension studies with leronlimab as a treatment for HIV.

December 24, 2020 - CytoDyn Inc. announced the U.S. FDA guided the Company through adding an open-label extension to its Phase 3 trial ("CD12") and specific criteria for the continuation of for patients meeting the inclusion/exclusion criteria of CD12. Upon clearance, each CD12 participating clinical trial site will have the option of enrolling additional qualified patients, with all patients receiving leronlimab. In addition, treatment of qualified patients will continue until the trial's data is unblinded.

December 15, 2020 - CytoDyn Inc. announced it had reached full enrollment in its Phase 3 registrational trial for patients with severe-to-critical COVID-19. The 390-patient data will be analyzed in approximately 28 days, with expected results announced shortly after that.

November 23, 2020 - CytoDyn Inc., a biotechnology company developing Vyrologix™ (leronlimab-PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today it had reached an enrollment of 293 patients in its Phase 3 trial for COVID-19 patients with severe-to-critical symptoms, thereby meeting the requested criteria for a second interim efficacy analysis by the Data Safety Monitoring Committee.

November 17, 2020 - Washington-based CytoDyn Inc. announced it had filed a protocol with the U.S. FDA for a Phase 2 clinical trial for leronlimab to treat COVID-19 patients suffering from long-hauler symptoms.

October 26, 2020 - CytoDyn Inc. announced the Medicines & Healthcare product Regulatory Agency of the U.K. government had cleared CytoDyn to file its Biologics License Application (BLA) leronlimab as a combination therapy for multi-drug resistance HIV patients in the U.K.

October 20, 2020 - CytoDyn Inc. announced recommendations from the Data Safety Monitoring Committee following its review of the interim analysis of the Company's Phase 2b/3 registrational trial in patients with severe-to-critical COVID-19. The interim analysis was performed on data from the first 195 (50%) of 390 planned patients.

September 22, 2020 - CytoDyn's Phase 2 Study of Leronlimab for Mild-to-Moderate COVID-19 Selected for Oral Presentation at the Special isirv-AVG Virtual Conference on 'Therapeutics for COVID-19.'

July 21, 2020 - CytoDyn Inc. announced the results of the patient safety data from the Company's over-enrolled COVID-19 disease Phase 2 trial for treating mild-to-moderate indications. Just 5 patients out of 56 (about 9%) reported serious adverse events; none were related to leronlimab.

May 19, 2020 - CytoDyn Inc. announced it would coordinate with the NIH of Mexico and provide leronlimab for a trial for the severe - critical COVID-19 disease population in Mexico with the potential to collaborate on further collaboration CytoDyn COVID-19 trials. "The NIH of Mexico is committed to helping alleviate human suffering and mortality of Mexican citizens. The Metropolitan Area of the Valley of Mexico has a population of approximately 21.5 million people, and the contagious nature of COVID-19 is relentless," said Nader Pourhassan, Ph.D., President, and Chief Executive Officer of CytoDyn.

May 5, 2020 - CytoDyn Inc. announced a pre-print version of the manuscript had been made publicly available on posting with Research Square and MedRxiv describing the immunological mechanism by which leronlimab restores immune function and impacts disease in COVID-19 patients. As described in the pre-print, in a cohort of ten critically ill patients, after treatment with leronlimab, these critically ill patients experienced reversed hyperimmune activation and inflammation. In addition, they reversed immunosuppression, thereby facilitating a more effective immune response correlated with decreases in SARS-CoV-2 levels in the blood.

May 4, 2020 - CytoDyn Requests Compassionate Use from FDA for COVID-19 Patients Not Eligible for Participation in Two Ongoing Clinical Trials in the U.S. – CytoDyn Targets Enrollment Completion for its 75 Patient, Phase 2 Trial by the end of May.

April 7, 2020 - Novant Health is initiating patient enrollment in CytoDyn's Phase 2 randomized clinical trial for COVID-19 patients with mild-to-moderate infections.  Novant Health is the first site in the southeastern United States to initiate this Phase 2 trial.  And a  Phase 2b/3 trial will be for severe and critically ill COVID-19 patients.

March 19, 2020 - CytoDyn Inc. announced today that two coronavirus patients were treated with the Company's investigational new drug, leronlimab. The treatment was administered at a leading medical center in the New York City area under an emergency Investigational New Drug (IND) recently granted by the U.S. Food and Drug Administration (FDA).

Vyrologix Leronlimab (Pro 140) Clinical Trials

Cytodyn's Vyrologix is being studied in 5 clinical trials. On August 2, 2021, Brazil authorized a phase 3 study. This pivotal Phase 3 trial for severe COVID-19 patients is conducted by Academic Research Organization ("ARO") Albert Einstein Israelite Hospital. This trial intends to provide Brazil's regulatory authority ANVISA (Agência Nacional de Vigilância Sanitária) with the requisite data to consider advancing the availability of leronlimab to Brazilians infected with COVID-19. The trial will be conducted in up to 35 clinical sites with 612 patients who are hospitalized and in need of oxygenation support.

On July 21, 2020, the Phase 2 study announced 34% (19 of 56 patients) were treated with leronlimab compared to 50% (14 of 28 patients) treated with placebo reported at least one adverse event. A total of 19 serious adverse events (SAEs) were reported during the study. Eleven SAEs were reported in 6 patients (6/28; 21.4%) receiving placebo compared to eight (8) SAEs in 5 patients (5/56; 8.9%) receiving leronlimab. None of the SAEs in the leronlimab arm were deemed related to study drug administration by the investigators. Of the 84 patients treated, one patient died 33 days after enrollment due to an event unrelated to leronlimab.

ClinicalTrials.gov Identifier: NCT04343651 - This is a Phase 2, two-arm, randomized, double-blind, placebo-controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection. Last updated on September 29, 2021.

CytoDyn is also conducting a Phase 2 clinical trial for NASH to evaluate the effect of leronlimab on liver steatosis and fibrosis. Pre-clinical studies revealed a significant reduction in NAFLD and a reduction in liver fibrosis using leronlimab.

To find out more about the clinical trials, please visit Cytodyn's clinical trial enrollment site.