CytoDyn Submits Breakthrough Therapy Designation Application to FDA for Leronlimab as a Treatment for Metastatic Triple-Negative Breast Cancer (mTNBC); Fast Track Designation for mTNBC was received previously

Ongoing analysis of data from 28 mTNBC patients following 12 months of treatment with leronlimab is very encouraging given little-to-no effective treatment options currently

VANCOUVER, Washington, Nov. 08, 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 it has submitted to the U.S. Food and Drug Administration (“FDA”) an application for Breakthrough Therapy designation (“BTD”) for leronlimab as a potential treatment for mTNBC. This BTD application is based on the data analysis reported by the Company on November 3, 2021.

The Company’s Chief Medical Officer, Scott Kelly, M.D., shared early findings from this study with the medical and scientific communities at the Triple-Negative Breast Cancer Drug Development Digital Summit in April 2021. Dr. Nitya Ray, CytoDyn’s COO and CTO, has led the BTD effort in collaboration with experts in Oncology, Biostatistics, and Regulatory affairs.

As previously reported, these findings represent the analysis of data from 28 pooled patients, 16 from our Compassionate Use Study, 10 from the Phase 1b/2 Study, and 2 from the Basket Study. All subjects received ≥1 dose of leronlimab (range 1-51 doses) subcutaneously in conjunction with standard of care (SOC) systemic chemotherapy. Of the 28 subjects, 9 subjects received 350mg weekly dose and 19 subjects received 525mg or 700mg weekly dose (4 subjects had dose escalation from 350mg to 525mg and were included in the higher dose cohort). The median age of the subjects was 52 years (range 33-84 years). All subjects were diagnosed with Stage IV mTNBC. Of the 28 subjects, 17 (61%) subjects started with visceral metastases, 6 (21%) subjects started with brain metastases, and 3 (11%) had bone-only metastases.
LifeTracDx™ liquid biopsy algorithm developed by Creatv MicroTech, Inc. was used to evaluate patient response to leronlimab treatment. The algorithm uses the following parameters: 1) Change in Circulating Tumor Cell (CTC) number, 2) Change in Cancer-Associated Macrophage-Like cell (CAML) number, and 3) Change in CAML size, at the blood draw at baseline and after first therapy.

Assessment of tumor response was performed according to RECIST, version 1.1 in patients with measurable legions prior to induction with leronlimab.

Key findings from a pooled analysis of efficacy data of 28 subjects with mTNBC, including those with brain or bone metastases, who had failed ≥ 2 lines of prior systemic therapies, are as follows:

• The median overall survival (mOS) for patients that received higher doses (≥ 525 mg) of leronlimab plus chemotherapy was 12+ months (95% CI, 5.5 – 12+ months), which is superior to SOC chemotherapy (6.6 months) or Sacituzumab Govitecan (SG) (11.8 months), an antibody drug conjugate that received accelerated approval by the FDA in 2020 and regular approval in 2021 for the treatment of patients with unresectable locally advanced or mTNBC who have received ≥ 2 prior systemic therapies. Previously SG received fast track and breakthrough therapy designations. 12% patients in the SG Phase III trial had brain metastasis.
• The mOS for patients that received leronlimab plus carboplatin was 12+ months (95% CI, 5.4 – 12+ months). There were 13 mTNBC patients in that group.
• The median progression-free survival (mPFS) for patients that received higher doses (≥ 525 mg) of leronlimab plus chemotherapy was 6.2 months (95% CI, 2.6 – 7.5 months), which is significantly longer compared to SOC chemotherapy (2.3 months) or SG (4.8 months).
• Available data from 12 subjects who had measurable lesions by PET/CT scans at baseline and after start of leronlimab induction, showed that 11 (92%) patients exhibited stable or partial response to leronlimab, with 3 (25%) PRs, 8 (66.7%) SDs and 1 (8%) having progressive disease after the first follow up scan.
• The LifeTracDx™ liquid biopsy algorithm clearly distinguishes responders to leronlimab. 75% of the patients who exhibited lower level of circulating cells after leronlimab or at baseline exhibited statistically significant improvement in mOS (Hazard Ratio (HR): 36.0 (95% CI, 6.2 – 207.6, p=0.0004)) and in mPFS (HR: 5.8 (95% CI, 1.4 – 23.6, p=0.0354)), respectively.

Nader Pourhassan, Ph.D., CytoDyn’s President and Chief Executive Officer, commented, “In our view, these findings provide strong support for our decision to submit an application for Breakthrough Therapy designation for leronlimab as a treatment for mTNBC. Patients with this horrific disease currently have few, if any, treatment options, and we hope that leronlimab can provide a therapeutic choice for substantially improved clinically relevant endpoints, quality of life, tolerability and safety over currently available SOC. We hope to receive a response from the FDA before the end of the year. 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.”

About Leronlimab
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 1b/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.

About CytoDyn
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, an integral step in the resubmission process for its BLA, which it expects to complete during the first calendar quarter of 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. 

Forward-Looking Statements 
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 obligations; (iv) the Company’s ability to enter into 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 Company’s ability to achieve approval of a marketable product; (vii) the design, implementation and conduct of the Company’s clinical trials; (viii) the results of the Company’s clinical trials, including the possibility of unfavorable clinical trial results; (ix) the market for, and marketability of, any product that is approved; (x) 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; (xi) regulatory initiatives, compliance with governmental regulations and the regulatory approval process; (xii) legal proceedings, investigations or inquiries affecting the Company or its products; (xiii) general economic and business conditions; (xiv) changes in foreign, political, and social conditions; (xv) stockholder actions or proposals with regard to the Company, its management, or its board of directors; and (xvi) 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.

Important Information
CytoDyn has filed with the SEC a definitive proxy statement and associated BLUE proxy card in connection with the solicitation of proxies for the Company’s 2021 Annual Meeting, which has been adjourned until November 24, 2021. Details concerning the nominees of the Company’s Board of Directors for election at the 2021 Annual Meeting are included in the proxy statement. BEFORE MAKING ANY VOTING DECISION, INVESTORS AND STOCKHOLDERS OF THE COMPANY ARE URGED TO READ ALL RELEVANT DOCUMENTS FILED WITH OR FURNISHED TO THE SEC, INCLUDING THE COMPANY'S DEFINITIVE PROXY STATEMENT AND ANY SUPPLEMENTS THERETO, BECAUSE THEY CONTAIN IMPORTANT INFORMATION.

Investors and stockholders can obtain a copy of the definitive proxy statement and other documents filed by the Company free of charge from the SEC's website, www.sec.gov. The Company's stockholders also can obtain, without charge, a copy of the definitive proxy statement and other relevant filed documents by directing a request by mail to CytoDyn Inc. at 1111 Main Street, Suite 660, Vancouver, Washington 98660.

CONTACTS

Investors:
Cristina De Leon
Office: 360.980.8524
ir@cytodyn.com

OR

Mike Verrechia / Bill Dooley, 800-662-5200
Morrow Sodali
cydy@info.morrowsodali.com

Melissa Carlson
Alliance Advisors
mcarlson@allianceadvisors.com
Shareholders Call Toll Free:  833-814-9456  

Media:
Dan Zacchei / Joe Germani
Sloane & Company
dzacchei@sloanepr.com / jgermani@sloanepr.com