After FDA hold, CytoDyn will appeal for pharma partnerships to save leronlimab

 With CytoDyn's lead drug on FDA clinical hold, the troubled biotech will go searching for partners to rescue key programs and keep afloat.

Meanwhile, the board is actively searching for a new CEO to replace Nader Pourhassan, Ph.D., who was ousted in January.

The company provided a sweeping corporate update in a conference call Thursday morning, after announcing at market close the day before that the FDA had placed two separate clinical holds on leronlimab. The regulatory shutdown includes a partial hold on CytoDyn’s HIV work and a full hold on the COVID-19 program, according to an after-market release issued Wednesday.

"We will be focused on setting up the company for future success by restoring credibility and determining our most advantageous path forward with the goal of maximizing shareholder value," said Antonio Migliarese, CFO and interim president, on the call.

Migliarese then listed the priorities, which were many: "We plan on doing this by strengthening our clinical operations and prioritizing patient safety, addressing the concerns noted in the partial clinical hold letter received for HIV and the full clinical hold letter received for COVID-19, enhancing leadership with the board, CEO and Scientific Advisory Board, addressing legal and financial issues."

Not to mention analyzing new data in HIV, revamping the timeline for a biologics license application in the indication, releasing results in non-alcoholic steatohepatitis and finding new partnerships with pharmaceutical companies to fund all this work. All that for a company that does not currently have a CEO.

CytoDyn has touted leronlimab as having potential in multiple indications, but the therapy has struggled in the clinic against COVID, and the company has equally faced difficulties in getting regulatory submissions locked down for HIV. The company said in announcing the holds that clinical trials underway in the COVID program in Brazil would be paused pending results from the data safety monitoring committee.

Chief Medical Officer and Head of Business Development Scott Kelly said the company decided to pause the Brazilian trials in COVID because of two cardiac events. The studies feature very sick patients with cardiac and pulmonary manifestations of the disease, he added.

The study remains blinded, meaning CytoDyn does not know whether the patients who suffered the cardiac events received leronlimab or placebo. 

"We discussed this in depth with the physician investigators in Brazil who have extensive pulmonary and critical care expertise, and they believe the events were consistent with the natural course of COVID and nothing out of the ordinary of their experience and prior COVID-19 trials," Kelly said. 

CytoDyn opted to pause the program "out of an abundance of caution," knowing that the data safety monitoring committee would be meeting anyway in April. 

"I want to be clear that this was our decision. We thought it was the right thing to do," Kelly said. Once the committee clears the trial to continue, CytoDyn plans to resume clinical activities.

As for the holds, Kelly said the agency wants aggregated safety data from all the indications leronlimab has been tested in before any further work can be done in the U.S. He called this a "solvable problem," and pledged to complete the work on an eight- to 10-week timeline. Kelly stressed that the company is not enrolling in the U.S. for the COVID program, and the HIV program at issue is a long-term extension study that has wrapped up. 

For the HIV program, CytoDyn said Wednesday that "these patients will be transitioned to other available therapeutics and no clinical studies can be initiated or resumed until the partial clinical hold is resolved." While the company works with the FDA to resolve the holds, no new studies may be started in the COVID-19 program.

The company will also re-evaluate a biologics license application in HIV, which will mean a "delay in clinical activities," according to Chris Recknor, M.D., senior executive VP of clinical operations. The submission will be on hold while the safety data is compiled for the FDA with a new CRO. 

Regarding the search for a new CEO, Board Chair Tanya Urbach said a search committee has been formed. 

"We are excited about the overall quality of the candidate pool and will continue in our efforts to identify the company's next chief executive officer," she said. 

CytoDyn also provided a broad update to its clinical programs, including plans to advance leronlimab in NASH. The company has also been contacted by multiple academic institutions for access to the drug to conduct preclinical studies in glioblastoma multiforme, Alzheimer's disease and others, according to Kelly. Another study could someday look at using leronlimab in COVID long haulers, and there's been interest in combining the therapy with CAR-T treatments in cancer, he said.

All of these indications have confounded major drugmakers for decades, even companies that specialize in diseases like NASH or Alzheimer's. 

For all or most of these initiatives, CytoDyn needs help. Kelly, and other executives said over and over that they would be seeking partnerships to move programs forward. This will help CytoDyn "advance our development efforts and value creation with minimal investment," according to Migliarese.

"As we all know, in clinical trials, it's very costly, but we believe we can leverage the experience of others that are experts in each chosen field," Kelly said. 

He declined to name names, but said, "We have companies under NDA right now and we are advancing those discussions for multiple different applications for leronlimab." 

Another issue that received scant mention is CytoDyn's many legal battles, which include an investigation from the Department of Justice and the Securities and Exchange Commission. Migliarese said the company is fully cooperating with the investigators and "doing our best to expeditiously wrap up the various other legal matters of the company." That includes a spat with a former contract research organization. 

CytoDyn's remaining leadership has a tough to-do list. But the conference call was markedly more sane compared to those previously held when Pourhassan was in charge. In May last year, he begged investors to stop trashing the FDA after the agency's public smackdown of the company over its leronlimab claims. Pourhassan took a barrage of questions from angry investors. But on today's call, Kelly and the team took pre-screened written questions, mostly those surrounding clinical trial updates or the pharma partnerships. 

https://www.fiercebiotech.com/biotech/cytodyns-leronlimab-slapped-fda-holds-covid-19-hiv-programs