Every second of every day, someone in the world attempts suicide.

NRx Pharmaceuticals is developing a drug for people whose suicidal thoughts stem from bipolar depression, the low mood phase associated with the severe mood swings of bipolar disorder.

If the clinical trials proceed as planned, the company hopes to commercialize the drug in 2024.

“Although bipolar depression accounts for only about 10 percent of all people who have depression, it accounts for about 40 percent of those who try to harm themselves,” says Dr. Jonathan Javitt, founder and chief scientist of NRx, the Nasdaq-listed company that merged with NeuroRx in 2021.

“Suicidal bipolar depression is a devastating disease and one that has not been addressed by pharmaceutical companies. There are no FDA-approved medicines today for people with suicidal bipolar depression.”

NRx’s multi-patented NRX-101 (Cyclurad) combines two FDA-approved pharmaceuticals: the tuberculosis drug D-cycloserine and the anti-infective drug lurasidone. It is meant to be taken orally at home.

Most conventional antidepressant drugs – which can actually increase risk of suicide — target the brain’s serotonin pathway. NRX-101 acts on the brain’s NMDA receptor, a newly validated target for treating suicidal ideation and depressive symptoms, particularly in bipolar depression.

A trial conducted at Herzog Hospital in Jerusalem showed a significant benefit of D-cycloserine (compared to placebo) in patients with treatment-resistant depression. And the effect of D-cycloserine in reducing suicidality was demonstrated in an independent trial in 2019.

NRx’s drug candidate is also beneficial following an injection of the anesthetic drug ketamine, which reverses depression but only for about four days. Ketamine cannot be given continuously because it causes psychedelic, addictive and neurotoxic side effects. NRX-101 sustains the anti-depressive effect of ketamine for two months without these undesirable side effects.

Lifetime of research

Javitt, an ophthalmologist by training, led drug development programs for eye diseases and diabetes over the past 40 years with Allergan, Eyetech, Merck, Novartis, Pfizer and Pharmacia.

But the research that served as the basis for NRx’s drug candidate began with his brother, Daniel, a Jerusalem-based psychiatrist.

“Early in my brother’s career in the 1990s, he set out to understand why an abuse drug called angel dust causes acute psychosis. He discovered that it’s because angel dust binds to the NMDA receptor in the brain,” says Jonathan Javitt.

He followed the unfolding research in this field, including Dr. Robert Berman’s discovery that drugs that bind to the NMDA receptor may profoundly relieve depression and suicidal thoughts.

“Daniel became one of the most published authors in this field of brain science,” says Javitt. “What we are doing is a natural outgrowth of that lifetime of research.”

Herzog Hospital, where the first clinical trial of NRX-101 was conducted, is one of the founding shareholders along with individuals including Chaim Hurvitz, former director of Teva and president of the Teva International Group.

Commercialization in 2024

When ISRAEL21c first wrote about the newly formed company in 2015, the idea that an NMDA antagonist drug could treat symptoms of depression was novel.

“Now it’s a well-validated idea,” says Javitt. “There are drugs in development, two approved by the FDA, so the science has become well accepted.”

The company’s progress on the psychiatric drug, however, was sidelined for about three years during the pandemic, when NRx was working with the Israel Institute for Biological Research on Covid-related developments.

The NRX-101 program got back on track about a year ago.

“We are still the only company focused on bipolar depression and specifically suicidal bipolar depression,” Javitt tells ISRAEL21c.

Based in Delaware, NRx completed an initial Phase II trial that led to FDA breakthrough therapy designation and a special protocol agreement.

“Now we’re in a registrational trial in people with suicidal bipolar depression,” says Javitt.

He notes that this is the first known trial of a novel antidepressant in which patients with active suicidal ideation have successfully been enrolled.

“We’re expecting to finish by the end of the year and we’ve already completed our manufacturing scaleup to be ready for commercialization. We aim for FDA approval toward the release of the drug to the market at 2024.”

The same drug is also being tested for preventing suicidal ideation in cases of PTSD and chronic pain in depression.

“Post-9/11, we have lost four times more [US military] veterans and servicemembers to suicide than combat,” notes Javitt, who was a healthcare adviser to four White House administrations.

NRx estimates the market potential of a bipolar depression treatment at $2.2 billion, given that about 7 million people are bipolar and 9-10% of them suffer from suicidal thoughts.

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