CytoDyn previously hit a primary endpoint in a pivotal Phase 3 HIV trial with some HTE patients; over 20 patients remain in an extension arm study for up to 4 years
CytoDyn will include some findings from this study in its BLA submission for HIV approval
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, today announced that a research paper entitled “Leronlimab (PRO 140) activity against 4-class drug resistant HIV-1 from Heavily Treatment Experienced Subjects” has been accepted, peer reviewed and is available as a journal pre-proof on ScienceDirect. ScienceDirect provides access to a large bibliographic database of scientific and medical publications of the Dutch publisher Elsevier. This article is available for purchase from Elsevier through a link on CytoDyn’s website:
LERONLIMAB (PRO 140) ACTIVITY AGAINST 4-CLASS DRUG RESISTANT HIV-1 FROM HEAVILY TREATMENT EXPERIENCED SUBJECTS - ScienceDirect
This project was a collaborative effort among scientists and researchers from:
- University of Milan, Milan, Italy
- University of Siena, Siena, Italy
- University of Rome Tor Vergata, Rome, Italy
- San Raffaele Vita-Salute University, Milan, Italy
- Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy
- Azienda Ospedaliera San Paolo, Milan, Italy
- University of Perugia, Perugia, Italy; 8 Santa Maria Annunziata Hospital, Florence, Italy; 9 University of Brescia, Brescia, Italy.
The study was conducted as an in-vitro study of 25 HIV-1-infected patients harboring a documented 4-class drug-resistance nucleoside reverse transcriptase inhibitors (“NRTIs”), non-nucleoside reverse transcriptase inhibitors (“NNRTIs”), protease inhibitors (“PIs”), and integrase strand transfer inhibitors (“INSTIs”) enrolled in the Italian PRESTIGIO Registry.
Significant findings from the study and observations from the authors include:
- Leronlimab maintained full activity in the presence of extensive resistance to the four main antiviral classes.
- Leronlimab IC50 did not appear significantly altered by previous or current exposure to maraviroc.
- In vitro, leronlimab and maraviroc have been reported to have synergistic activity, further corroborating the different mechanism of the two drugs despite the same CCR5 target.
- In vitro susceptibility to leronlimab is not affected by extensive drug resistance and exposure to maraviroc.
- Leronlimab may have some advantages over maraviroc as a clinically valuable CCR5 antagonist, including lower toxicity, less drug-drug interaction issue and less frequent dosing.
- Leronlimab can play a key role in subjects with very limited therapeutic options and CCR5-tropic virus.
“We would like to thank our Italian colleagues for understanding the importance of leronlimab in the treatment of HIV. This is further proof that leronlimab can benefit CCR5 tropic HIV patients, including those patients with multidrug resistance. HIV patients deserve the opportunity for multiple, effective treatment options,” said CytoDyn’s Chief Medical Officer, Scott A. Kelly M.D.
Nader Pourhassan, Ph.D., CytoDyn’s President and Chief Executive Officer, commented, “I would like to thank Dr. Stefano Rusconi, who had reached out to us to do this study. We are grateful to him and his colleagues for producing what we believe to be further evidence that leronlimab can play a vital role in the treatment of HIV. We believe leronlimab has many advantages, including protecting healthy cells from viral entry, prevention of HIV transmission, convenience, lower toxicity, and the ability to treat patients across the full spectrum of disease from treatment-naive to 4-class resistant HIV. Many HIV patients could also be in danger of developing NASH and, with our recent 350 mg open label NASH trial having achieved its primary (PDFF) and secondary (cT1) endpoints, we believe that all HIV patients may benefit from a CCR5 product as part of their medication. We also believe leronlimab’s potential role in cancer treatment could help HIV patients with a long history of HIV (especially heavily treatment experienced HIV), which increases their risk of developing cancer.”
The U.S. Food and Drug Administration (FDA) granted CytoDyn Fast Track designation to explore two potential indications using leronlimab to treat Human Immunodeficiency Virus (HIV) and metastatic cancer. The first indication is combination therapy with HAART for HIV-infected patients, and the second is for metastatic triple-negative breast cancer (mTNBC). Leronlimab is an investigational humanized IgG4 mAb that binds to CCR5, a cellular receptor important in HIV infection, tumor metastases, and other diseases, including nonalcoholic steatohepatitis (NASH). Leronlimab has been studied in 16 clinical trials involving more than 1,200 people and met its primary endpoints in a pivotal Phase 3 trial (leronlimab combined with HIV standard care in patients with multi-drug resistance to current available classes of HIV drugs).
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. Five clinical trials have demonstrated leronlimab could significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent with fewer side effects and less frequent dosing requirements than currently used daily drug therapies. Cancer research has shown CCR5 may play a role in tumor invasion, metastases, and tumor microenvironment control (for example, through angiogenesis). Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 97% in a murine xenograft model. As a result, CytoDyn is conducting two clinical trials, one, a Phase 2 in mTNBC, which was granted Fast Track designation by the FDA in 2019, and a second, a Phase 2, basket trial which encompasses 22 different solid tumor cancers.
The CCR5 receptor plays a central role in modulating immune cell trafficking to sites of inflammation. After completing two clinical trials with COVID-19 patients (a Phase 2 and a Phase 3), CytoDyn initiated a Phase 2 investigative trial for post-acute sequelae of SARS COV-2 (PASC), also known as COVID-19 Long-Haulers. This trial evaluated the effect of leronlimab on clinical symptoms and laboratory biomarkers to further understand the pathophysiology of PASC. It is currently estimated that between 10-30% of those infected with COVID-19 develop long-term sequelae. Common symptoms include fatigue, cognitive impairment, sleep disorders, and shortness of breath. CytoDyn plans to pursue clinical trials to evaluate leronlimab’s effect on immunological dysregulation in other post-viral syndromes, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
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 transplant. About 30 to 40 percent of adults in the U.S. live with NAFLD, and 3 to 12 percent of adults in the U.S. live with NASH. There have been no strong safety signals identified in patients administered leronlimab in multiple disease spectrums, including patients with HIV, COVID-19, and oncology.
CytoDyn 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 and appears to be implicated in tumor metastasis and immune-mediated illnesses, such as NASH.
CytoDyn successfully completed a Phase 3 pivotal trial using leronlimab combined with standard antiretroviral therapies in HIV-infected patients who were heavily treatment-experienced individuals with limited treatment options. CytoDyn is working diligently to resubmit its Biologics License Application ("BLA") for this HIV combination therapy since receiving a Refusal to File in July 2020. In July 2021, CytoDyn announced that it had submitted a dose justification report to the FDA, and in November 2021 resubmitted the non-clinical and manufacturing sections of the BLA, all integral steps in the BLA resubmission process, which it expects to complete by the end of the first quarter of calendar 2022. CytoDyn also completed a Phase 2b/3 investigative trial with leronlimab used as a once-weekly monotherapy for HIV-infected patients. CytoDyn plans to initiate a registration-directed study of leronlimab monotherapy indication. If successful, it could support a label expansion approval. Clinical results to date from two trials have shown that leronlimab can maintain a suppressed viral load in a sub-population of R5 HIV patients who chose to switch from their daily pills regimen to once-a-week subcutaneous dose of leronlimab. Several patients on leronlimab’s Phase 2b extension arm have remained virally suppressed for almost 7 years and many patients in our Phase 2b/3 investigative trial are passing two and some four years of monotherapy with suppressed viral load.
CytoDyn is also conducting a Phase 2 clinical trial with leronlimab in mTNBC, a Phase 2 basket trial in solid tumor cancers (22 different cancer indications), Phase 2 investigative trial for post-acute sequelae of SARS COV-2, also known as COVID-19 long haulers, and a Phase 2 clinical trial for NASH. CytoDyn has already completed a Phase 2 and Phase 3 trial for mild-to-moderate and severe-to-critical COVID-19 patients, respectively, for which CytoDyn did not meet its primary or secondary endpoints except for the secondary endpoint in the critically ill subpopulation. More information is at www.cytodyn.com.
This press release contains certain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects, as well as words such as "believes," "hopes," "intends," "estimates," "expects," "projects," "plans," "anticipates" and variations thereof, or the use of future tense, identify forward-looking statements, but their absence does not mean that a statement is not forward-looking. Forward-looking statements specifically include statements about leronlimab, its ability to provide positive health outcomes, the possible results of clinical trials, studies or other programs or ability to continue those programs, the ability to obtain regulatory approval for commercial sales, and the market for actual commercial sales. The Company's forward-looking statements are not guarantees of performance, and actual results could vary materially from those contained in or expressed by such statements due to risks and uncertainties including: (i) the regulatory determinations of leronlimab’s efficacy to treat human immunodeficiency virus (“HIV”) patients with multiple resistance to current standard of care, COVID-19 patients, and metastatic Triple-Negative Breast Cancer (“mTNBC”), among other cancer indications, by the U.S. Food and Drug Administration and various drug regulatory agencies in other countries; (ii) the Company’s ability to raise additional capital to fund its operations; (iii) the Company’s ability to meet its debt and other payment obligations; (iv) the Company’s ability to enter into or maintain partnership or licensing arrangements with third-parties; (v) the Company’s ability to identify patients to enroll in its clinical trials in a timely fashion; (vi) the timely and sufficient development, through internal resources or third-party consultants, of analyses of the data generated from the Company’s clinical trials required by the FDA or other regulatory agencies in connection with the Company’s BLA resubmission or other applications for approval of the Company’s drug product; (vii) the Company’s ability to achieve approval of a marketable product; (viii) the design, implementation and conduct of the Company’s clinical trials; (ix) the results of the Company’s clinical trials, including the possibility of unfavorable clinical trial results; (x) the market for, and marketability of, any product that is approved; (xi) the existence or development of vaccines, drugs, or other treatments that are viewed by medical professionals or patients as superior to the Company’s products; (xii) regulatory initiatives, compliance with governmental regulations and the regulatory approval process; (xiii) legal proceedings, investigations or inquiries affecting the Company or its products; (xiv) general economic and business conditions; (xv) changes in foreign, political, and social conditions; (xvi) stockholder actions or proposals with regard to the Company, its management, or its board of directors; and (xvii) various other matters, many of which are beyond the Company’s control. The Company urges investors to consider specifically the various risk factors identified in its most recent Form 10-K, and any risk factors or cautionary statements included in subsequent Form 10-Qs and Form 8-Ks, filed with the Securities and Exchange Commission. Except as required by law, the Company does not undertake any responsibility to update any forward-looking statements to take into account events or circumstances that occur after the date of this press release.
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