Embattled CytoDyn sets new course toward NASH, tough tumors
Published: Mar 15, 2023
By Heather McKenzie
CytoDyn has spent the past two years under siege – from the FDA, disgruntled investors and by association, the U.S. Department of Justice. Now, the company’s leadership hopes to chart a new future in non-alcoholic fatty liver disease (NASH).
In May 2021, the Vancouver, Wash.-based biotech was taken to task by the FDA in a rare public scolding over misleading claims of efficacy of its sole asset, leronlimab, in COVID-19.
Before this doomed attempt, CytoDyn was developing the antibody for HIV. In October 2022, the company withdrew its Biologics License Application in this indication, citing concerns regarding the contract research organization managing its trials.
Finally, in December 2022, the DOJ indicted Nader Pourhassan, former CytoDyn CEO and Kazem Kazempour, CEO of Amarex Clinical Research, which managed CytoDyn’s clinical trials, on multiple counts of fraud. CytoDyn terminated Pourhassan in January 2022.
Cyrus Arman, Ph.D., was installed as CEO in July 2022 in an effort to turn the page. Arman spoke with BioSpace in an exclusive interview.
He first addressed the company’s recent history.
“I think a lot of it had to do with the prior management’s lack of experience in the drug development space,” he said. “Having a CEO that wasn’t trained in the industry, didn’t come from the industry and had no real experience operating in a regulated environment…led to a series of missteps.”
Arman also cited a lack of discipline around the clinical development strategy.
“Pursuing half a dozen different disease areas simultaneously with limited resources landed [management] in a position where they were able to generate pockets of data that were interesting, but probably not quite robust enough to do anything with.”
Arman said these issues overshadowed the real story – leronlimab.
Leronlimab is a humanized monoclonal antibody that can be delivered via subcutaneous injection or intravenously. It binds competitively to the C-C chemokine receptor type 5 (CCR5) receptor, a protein on the surface of some immune cells. This differs from the more common allosteric inhibitors of CCR5.
When he was initially approached about the opportunity, Arman separated his due diligence into two parts: the science behind leronlimab on one; the management issues and finance and legal components on the other.
Following this assessment, “I was really convinced that leronlimab is the real deal,” he said.
Focus on NASH
CCR5 is thought to play a role in myriad disease processes – among them one of biopharma’s hottest targets: NASH. In the liver, the CCR5 receptor is positioned on the surface of hepatocytes and stellate cells. When activated, hepatic stellate cells promote the deposition of collagen, which drives liver fibrosis.
As the only antibody in development that binds CCR5, Arman said leronlimab can directly regulate the production of collagen.
In a14-week, Phase II trial, leronlimab met the primary endpoint of proton density fat fraction (PDFF), an MRI-derived biomarker for fatty deposition.
In addition, “By working through the hepatic stellate cells, we believe we are seeing signals that we can actually reduce and potentially reverse the fibrosis,” Arman said. He added that he is encouraged by these positive signals after just 14 weeks.
CytoDyn plans to request an end of Phase II meeting with the FDA and will then look ahead to a longer Phase III trial.
First, however, the company must get leronlimab released from the clinical hold it is currently under.
In March 2022, the FDA placed a partial hold on CytoDyn’s HIV program and a full clinical hold on its COVID-19 program in the U.S.
The FDA identified five distinct areas it wanted the company to remediate. CytoDyn has addressed and submitted documentation for all five, Arman said. The regulator then came back in February with a sixth item, for which the company has since submitted documentation. Arman hopes to hear back “in the very near term” about having the hold lifted.
Addressing the Issues
Not all leaders would be up for this type of challenge, but Arman said he saw a “unique opportunity” to come in and help turn CytoDyn around.
“Obviously, the issues stemming from the past management are not trivial, but I do see them as being absolutely addressable,” he said.
To this end, Arman is actively working to bring in “industry entities who are qualified for their roles.”
Also key for Arman is to narrow the company’s clinical development focus.
Along with NASH, CytoDyn will focus primarily on oncology. Here, the company will target colorectal cancer and hormone receptor-positive, HER2-negative breast cancer.
These are both areas where checkpoint inhibitors have failed to show efficacy when added to a standard-of-care backbone, Arman said, adding that leronlimab has shown positive signals in both.
“From a mechanistic standpoint, we believe we could get a synergistic effect with a checkpoint inhibitor,” he said.
Leronlimab is currently being trialed in combination with Keytruda (pembrolizumab) in a breast cancer xenograft model in partnership with MD Anderson Cancer Center.
Arman said CytoDyn expects to observe an enhanced anti-tumor effect from the combination and identify immunological biomarkers.
In terms of future partnerships, Arman isn’t concerned that CytoDyn’s history will have a negative effect.
“I think that most companies are data-first,” he said. “If we come and we show the data that we have…I think they’ll see, here’s an organization that has transformed from what it used to be.”