CytoDyn will file for expanded access IND for patients with pancreatic, prostate, lung, breast, liver and melanoma cancers
VANCOUVER, Washington, Nov 19, 2019 — CytoDyn Inc. (otc.qb:CYDY), (“CytoDyn” or the “Company”), a late stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today that leronlimab inhibited a human colon carcinoma cell line, SW480 cells, metastases to liver and lung in a well-accepted mouse model. These human colon carcinoma cells were implanted in the colon walls of immunodeficient mice and treated with a control antibody or leronlimab. After four weeks, the mice were sacrificed and the lungs and livers removed for analysis of invasion of the colon cancer cells. Leronlimab produced statistically significant inhibition of metastases to lung and liver in this mouse model.
“This is additional preclinical data supporting the clinical programs that CytoDyn has underway in the oncology space,” stated CytoDyn President and CEO, Nader Pourhassan, Ph.D. “We plan to take advantage of the recent FDA recommended Master Protocol design. Under the Master Protocol design option, we will use the Basket Trial alternative for single therapeutic agents with enrollment of different cancer histologic types when a single biomarker is identified. In our case, patients with metastatic disease of different histologic types, all expressing CCR5, will be enrolled,” concluded Dr. Pourhassan.
Bruce Patterson, M.D., Chief Executive Officer of IncellDX and science advisor to CytoDyn stated: “CytoDyn will file for expanded access IND for patients with pancreatic, prostate, lung, breast, liver or melanoma cancers because we have been able to detect immune cell infiltrates expressing CCR5 that could impair the immune response against the tumor if CCR5 is not blocked. Having the ability to detect and quantify these target cell infiltrates puts leronlimab squarely in the personalized immune-oncology arena with a mechanism of action common to many tumors.”
The U.S. Food and Drug Administration recently announced the availability of a draft guidance for industry entitled “Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics.” This guidance provides advice to sponsors of drugs and biologics for cancer treatment regarding the design and conduct of clinical trials, other than first-in-human (FIH) trials, intended to simultaneously evaluate more than one investigational drug and/or more than one cancer type within the same overall trial structure (master protocols) in adult and pediatric cancers. In contrast to traditional trial designs, where a single drug is tested in a single disease population in one clinical trial, master protocols use a single infrastructure, trial design, and protocol to simultaneously evaluate multiple drugs and/or disease populations in multiple substudies, allowing for efficient and accelerated drug development. One example of the types of master protocol designs includes trials commonly referred to as basket trials.
A Basket Trial involves a single investigational drug or drug combination that is studied across multiple cancer populations defined by disease stage, histology, number of prior therapies, genetic or other biomarkers, or demographic characteristics. It is usually designed as a single-arm, activity-estimating trial with overall response rate as the primary endpoint. A strong response signal seen in a sub-study may allow for expansion to generate data that could potentially support a marketing approval.
CytoDyn has also recently been cleared by the FDA for a Phase 2 protocol to proceed for combination therapy of leronlimab and Regorafenib in patients with metastatic colorectal cancer (mCRC).
About Leronlimab (PRO 140)
The U.S. Food and Drug Administration (“FDA”) has granted a “Fast Track” designation to CytoDyn for two potential indications of leronlimab for deadly diseases. The first as a combination therapy with highly active antiretroviral therapy (“HAART”) for HIV-infected patients, and the second is for metastatic triple-negative breast cancer. Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases, including non-alcoholic steatohepatitis (“NASH”). Leronlimab has successfully completed nine clinical trials in over 800 people, including meeting its primary endpoints in a pivotal Phase 3 trial (leronlimab in combination with standard anti-retroviral therapies in HIV-infected treatment-experienced patients).
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 can significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements compared with daily drug therapies currently in use.
In the setting of cancer, research has shown that CCR5 plays a vital role in tumor invasion and metastasis. Increased CCR5 expression is an indicator of disease status in several cancers. 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 98% in a murine xenograft model. CytoDyn is, therefore, conducting a Phase 2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019. CytoDyn is conducting additional research with leronlimab in the setting of oncology and NASH with plans to conduct further clinical studies when appropriate.
The CCR5 receptor appears to play a central role in modulating immune cell trafficking to sites of inflammation. It may be important in the development of acute graft-versus-host disease (“GvHD”) and other inflammatory conditions. Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells. CytoDyn is currently conducting a Phase 2 clinical study with leronlimab to support further the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD. Blocking the CCR5 receptor from recognizing specific immune signaling molecules is a viable approach to mitigating acute GvHD. The FDA has granted “orphan drug” designation to leronlimab for the prevention of GvHD.
CytoDyn is a biotechnology company developing innovative treatments for multiple therapeutic indications based on leronlimab, a novel humanized monoclonal antibody targeting the CCR5 receptor. CCR5 appears to play a crucial role in the ability of HIV to enter and infect healthy T-cells. The CCR5 receptor also appears to be implicated in tumor metastasis and immune-mediated illnesses, such as GvHD and NASH. CytoDyn has completed a Phase 3 pivotal trial with leronlimab in combination with standard anti-retroviral therapies in HIV-infected treatment-experienced patients. CytoDyn plans to seek FDA approval for leronlimab in combination therapy and plans to complete the filing of a Biologics License Application (“BLA”) in 2019 for that indication. CytoDyn is also conducting a Phase 3 investigative trial with leronlimab as a once-weekly monotherapy for HIV-infected patients. CytoDyn plans to initiate a registration-directed study of leronlimab monotherapy indication, which, if successful, could support a label extension. Clinical results to date from multiple trials have shown that leronlimab can significantly reduce viral burden in people infected with HIV with no reported drug-related serious adverse events (SAEs). Moreover, results from a Phase 2b clinical trial demonstrated that leronlimab monotherapy can prevent viral escape in HIV-infected patients. Some patients on leronlimab monotherapy have viral suppression for more than four years. CytoDyn is also conducting a Phase 2 trial to evaluate leronlimab for the prevention of GvHD and has received clearance to initiate a clinical trial with leronlimab in metastatic triple-negative breast cancer. More information is at www.cytodyn.com.
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