While long-COVID is poorly understood, one clue is the detection of the pathogenic W-ENV protein in patients: and it is this that GeNeuro is targeting with its anti-W-ENV antibody.
Understanding long-COVID
Long-COVID is believed to affect around 16 million working-age Americans, with as many of 4 million of these out of work because of the disease, according to the Brookings Institution.
Development of treatments for long-COVID has proved a challenge because the very nature of the affliction is still poorly understood, as is the condition’s root cause. And because of this knowledge gap, treatments to date have focused on addressing symptoms rather than root causes.
However, one advance in understanding long-COVID has been the detection of the pathogenic W-ENV protein in patients: which is triggered by SARS-CoV-2 infection and has been found in more than 25% of patients with long-COVID. This protein can easily be detected with a blood test.
GeNeuro – a biotech headquartered in Geneva and with its R&D headquarters in Lyon, France –believes W-ENV plays a ‘major role’ in long-COVID.
“W-ENV protein is only found in situations of disease, such as acute Covid or long-Covid, but not in healthy persons,” Jésus Martin-Garcia, CEO of GeNeuro, told us.
“The pathogenic properties of W-ENV are well documented in the literature, activating innate immunity via the TLR4 pathway, and with a direct pathogenic effect on nervous system cells.
"Finding it in brain tissue and blood circulation of long-COVID patients, now up to two years after the original infection, may explain some of the observed phenomena such as cytokine upregulation and tissue damage in the central nervous system.”
The company has therefore developed temelimab, an anti-W-ENV antibody, as a Disease Modifying Therapy in long-COVID patients suffering from concentration or fatigue problems. A new Phase 2 trial will assess the efficacy of the treatment over a six-month trial of 200 patients across five Swiss centers.
To be eligible to participate in the study, participants must have confirmed presence of the W-ENV protein, alongside other specific clinical inclusion criteria – such as objective and subjective neuropsychiatric symptoms which hamper the pursuit of daily living and professional activities.
Gathering data on W-ENV
Martin-Garcia says that the 25% incidence of W-ENV in patients with long-COVID is a very conservative estimate: hence why the company is convinced it is a promising target for treatments.
“We have detected W-ENV in several long-COVID cohorts form the US and the EU. There were 25 to 50% of patients positive depending on the cohorts. We have conservatively planned for 25% in the clinical trial, and we will see “real-life” numbers as we progress with recruitment.
“That said, there are indeed most certainly other factors, which are not mutually exclusive. For example, damage sustained during the acute phase from which some patients have difficulty recovering. There is also emerging evidence that in some patients there could be reservoirs of SARS-CoV-2 remaining after the infection. Another concept, relevant for our study, is that the infection has caused in some patients a long-term immune imbalance, and W-ENV is a prime candidate to be the key mediator of this imbalance. And some patients may have several of these factors at play.”
The trial, therefore, will help understand the nature of this protein and the effect of removing it.
“To say it simply, having the W-ENV protein in the blood is a pathological finding and is not good for a patient, as it is only associated with severe autoimmune and neurodegenerative diseases. Neutralizing this protein with temelimab, an anti-HERV-W antibody with a very good tolerability profile, is a good thing to do to stop inflammation and damage to the central nervous system. The clinical trial will be able to determine if this treatment resolves, in part or in full, the very invalidating symptoms these patients suffer.”
Work with MS and ALS
Founded in 2006, GeNeuro‘s mission is to develop safe and effective treatments against neurological disorders and autoimmune diseases, such as multiple sclerosis, by neutralizing causal factors encoded by human endogenous retroviruses (HERVs), which represent 8% of human DNA.
Last month, the company presented Phase 2 data evaluating the administration of temelimab in patients with relapsing remitting MS: which met the key objective of showing that temelimab could bring additional benefits on key markers of neurodegeneration in patients already treated with an anti-inflammatory drug.
Meanwhile, a pre-clinical development program is targeting ALS with a new anti-HERV-K ENV antibody (GNK301).
“Our focus is leveraging the biology of human endogenous retroviruses, of which W-ENV is part, to bring novel solutions in neurodegenerative and autoimmune diseases, with some successes like our Phase II data against neurodegeneration in MS,” explained Martin-Garcia.
“We decided to start a program against long-COVID based on the evidence that SARS-CoV-2 triggers the expression of W-ENV in susceptible individuals, albeit with a very different pattern than in the other diseases we work on. In COVID, W-ENV appears to be highly expressed in the vascular system by lymphocytes and endothelial cells, which is for example not the case for W-ENV in MS, nor for K-ENV in ALS where the expression is predominantly in the central nervous system.
“We have been able to act fast because we already had an anti-W-ENV antibody we have developed for MS, and over 500 patient-years of clinical experience with it, showing an excellent tolerability profile.”
