Two For One

CytoDyn seeks to evaluate PRO 140 in breast cancer and NASH

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VANCOUVER—CytoDyn Inc. is sharing news of its own version of a “two for one” deal as it progresses PRO 140, also known as leronlimab, in both cancer and non-alcoholic steatohepatitis (NASH).
PRO 140, an investigational humanized IgG4 monoclonal antibody, is a CCR5 antagonist being explored in a variety of therapeutic indications. CCR5 has been implicated in several disease states. In cancer, it’s thought to play a role in tumor invasion and metastasis, with increased CCR5 expression being seen as an indicator of disease status. CCR5 inhibitors have been shown to be able to block tumor metastases in laboratory and animal models of breast and prostate cancer.
In a mouse xenograft human breast cancer metastatic model, mice treated with leronlimab continued to have a greater than 98 percent reduction in metastatic burden after nine weeks, compared with untreated mice at eight weeks. In addition, four of the mice in the control group that had advanced metastatic disease were treated with leronlimab, and two of them were still alive at week 16. CytoDyn noted in a press release that the data support an Orphan Drug Designation filing for leronlimab in metastatic triple-negative breast cancer (mTNBC).
CCR5 also impacts immune cell trafficking to sites of inflammation, with some companies exploring its role in graft-versus-host disease—clinical studies have shown that inhibiting CCR5 can reduce the impact of acute graft-versus-host disease without seriously hampering the engraftment of transplanted bone marrow stem cells.
It also is being explored in HIV/AIDS, where it plays a role in infection. Leronlimab, like other viral-entry inhibitors, masks CCR5 and, as a result, protects healthy T cells from infection by blocking the predominant HIV (R5) subtype from entering cells.
“We anticipate presenting the findings at an appropriate medical conference and publish[ing] the results,” said Dr. Richard G. Pestell, chief medical officer of CytoDyn. “Should our mouse xenograft breast cancer metastasis studies using leronlimab correlate in humans, leronlimab may offer paradigm-shifting treatment options for metastatic cancer patients. We look forward to interim data from our first human trial in mTNBC this year that will inform our future development and regulatory strategy.”
Given the results so far, CytoDyn is planning to expand preclinical animal studies in eight different cancer types.
Other recent news from CytoDyn details the company’s efforts to explore CCR5 not in treatment, but prevention. On May 13, the company announced an agreement with Dr. Daniel Lindner of The Cleveland Clinic to evaluate leronlimab’s ability to prevent non-alcoholic steatohepatitis (NASH) in humanized mouse models. The two organizations have initiated a preclinical study to explore this approach.
The CCR5 pathway has been identified as a potentially significant target in NASH. In a number of studies, CCR5 compounds have demonstrated anti-inflammatory and anti-fibrotic effects in NASH. Rather importantly for its potential in this indication, leronlimab has not shown the kind of liver toxicity demonstrated by other CCR5 antagonists.
“We are extremely fortunate and excited to partner with The Cleveland Clinic and Dr. Daniel Lindner to explore the potential of leronlimab in the prevention of NASH,” stated Dr. Nader Pourhassan, CytoDyn’s president and CEO. “A successful proof-of-concept study of leronlimab in NASH will allow the company to immediately file with the FDA an IND and protocol for a Phase 2 trial, as we have done with other indications. We are encouraged with Pfizer’s (Maraviroc) results in this field and we look forward to sharing the results of our study, as soon as it is available.”
A 2014 paper on Maraviroc, published in the Journal of Antimicrobial Chemotherapy, noted that “Higher levels of CCL5 mRNA have been observed in the livers of HCV patients with an advanced stage of liver injury. Indeed, Seki et al. showed that CCL5 promotes hepatic inflammation and fibrosis in two different models of experimental fibrogenesis. Furthermore, increased hepatic CCL5 expression in a murine model of hepatic steatosis and in obese patients has been reported. CCL5 is a natural ligand for the chemokine receptor CCR5. CCR5 also plays a central role in all the events related to the remodelling of liver matrix, and it has been observed that patients with chronic liver disease show high levels of CCR5 and CCL5. In addition, gene targeting or the use of a potent antagonist for the murine CCR5 results in a significant reduction of liver fibrosis and hepatocellular carcinoma.”
NASH and non-alcoholic fatty liver disease (NAFLD), its predecessor, are inflammatory diseases characterized by a build-up of fat in the liver, which leads to liver fibrosis. If untreated, the fibrosis can progress to cirrhosis, or liver scarring, which in turn can progress to hepatocellular carcinoma.

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