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GeNeuro Testing Efficacy of Antibody Temelimab in Long COVID Patients With W-ENV Protein

Sick and exhausted woman spending day at home

NEW YORK – Swiss biopharmaceutical company GeNeuro is exploring whether a monoclonal antibody it developed for multiple sclerosis can treat a biomarker-defined subset of patients with post-acute sequelae of SARS-CoV-2 infection, otherwise known as long COVID.

GeNeuro develops therapies that target human endogenous retroviruses (HERVs), which are remnants of viruses that long ago integrated into the DNA of individual cells and have since been passed down through an infected person's descendants. Today, an estimated 8 percent of human DNA is made of HERVs — "remains of the viral infections that have contaminated our ancestors," said GeNeuro CEO Jesús Martin-Garcia. Most of these DNA changes aren't harmful, but in some cases, new viral infections might activate HERVs that encode for pathogenic proteins and trigger immune responses linked with various neurological and autoimmune diseases.

GeNeuro is now studying whether temelimab, a drug that has already shown promising activity in multiple sclerosis patients in Phase II trials, can be used to treat patients with long COVID who have neuropsychiatric symptoms, fatigue, mobility challenges, and pain. Investigators last year began recruiting long COVID patients in a Phase II trial of the drug, which is designed to neutralize the HERV-W envelope (W-ENV) protein.

Unlike other treatment approaches for long COVID, temelimab is a disease-modifying therapy and isn't just treating the condition's symptoms, according to Martin-Garcia. While he is confident in the drug's ability to neutralize the W-ENV protein based on its performance in multiple sclerosis trials, another condition that's been linked to the presence of W-ENV, Martin-Garcia said it's not yet clear the extent to which doing so will address health issues related to long COVID — the focus of the trial. But the W-ENV protein may well be a key factor in the inflammatory cascade that patients experience, he hypothesized.

While most COVID-19 patients fully recover after the acute infection, at least 10 percent continue to experience disease symptoms, according to a survey by the US Census Bureau and the Centers for Disease Control and Prevention's National Center for Health Statistics. It's unclear why some patients fully recover while others don't.

The presence of the W-ENV protein may be one explanation, at least for the patients who have it. Researchers have found high levels of the W-ENV protein in leukocytes of some COVID-19 patients, the presence of which were correlated with inflammatory markers and other symptoms, according to study findings published in eBioMedicine in 2021. And about one-quarter of patients reporting long COVID, but who hadn't been hospitalized during their acute COVID-19 infection, have tested positive for the W-ENV protein, according preprint study results funded by GeNeuro and posted to the preprint server medRxiv this month.

That prevalence matches the observations of Gregory Fretz, head physician of the medical policlinic at the Kantonsspital Graubünden, a hospital in Switzerland, and a principal investigator on the temelimab long COVID trial. Based on biomarker screenings of potential participants in the trial, he said that between 20 percent and 25 percent of the long COVID patients he's seen have the W-ENV protein.

For research purposes, the US Department of Health and Human Services, the CDC, and others have jointly defined long COVID "as signs, symptoms, and conditions that continue or develop after initial COVID-19 or SARS-CoV-2 infection." The multisystemic and progressive symptoms continue for at least four weeks after a COVID-19 infection but can linger for months or even years. The varied and often unquantifiable nature of the symptoms can cause difficulties for patients, both medically and socially, Fretz noted. People in patients' daily lives might not believe their symptoms.

"If you just see these patients, at a first look, they seem healthy," despite the fact that they're suffering from various impairments, including fatigue and memory problems reminiscent of other serious neurodegenerative diseases, like Alzheimer's, he said. "A lot of patients really were — and still are — suffering in despair because there's no medical treatment."

In GeNeuro's trial, investigators will randomize about 200 patients at multiple sites in Italy, Spain, and Switzerland to receive either temelimab or placebo. The trial is limited to patients who had a COVID-19 infection but didn't undergo intensive treatment and have a positive blood test for the W-ENV protein.

Study participants will receive monthly IV infusions of temelimab over 24 weeks, totaling six infusions per person. Each infusion takes about two hours, Fretz said. Investigators will primarily evaluate participants for improvements in cognitive impairment or fatigue, with other secondary outcomes including measures of anxiety, depression, and quality of life.

GeNeuro expects to have a data readout from the trial in the first half of 2024.

Since temelimab is a "first-in-class" drug, GeNeuro won't be able to rely on a well-trodden regulatory path, Martin-Garcia said. There aren't marketed tests for readily gauging W-ENV in patients, so the company is planning to develop a companion diagnostic to identify long COVID patients eligible for temelimab.

Martin-Garcia noted that GeNeuro may consider partnerships or licensing deals with larger companies to expedite development of the drug and companion test. Should trial results be positive, he expects to apply for emergency marketing authorization with a confirmatory Phase III/IV study. The company will likely initially prioritize market approval in the countries where the temelimab clinical trial is already underway — Switzerland, Italy, and Spain — but will subsequently expand to markets including the US.

"We would like to push forward rather rapidly," Martin-Garcia said. "There's a tremendous medical need."