BioVie completes treatment phase of bezisterim Long COVID trial
BioVie Inc. has completed the treatment phase of its ADDRESS-LC Phase 2 trial evaluating bezisterim (NE3107) in adults with neurological symptoms associated with Long COVID, including brain fog, fatigue, and post-exertional malaise. The Nevada-based clinical-stage company said the final patient's on-treatment visit has taken place and that a one-month virtual follow-up is nearly complete. Topline results are expected before the end of September 2026.
The trial, which enrolled approximately 200 participants, is a randomised, placebo-controlled, proof-of-concept study comparing bezisterim administered as a 20 mg oral capsule twice daily against placebo. Primary endpoints cover overall clinical benefit alongside subjective and objective measures of cognitive function, fatigue, sleep disturbance, quality of life, and post-exertional malaise. Notably, the study is fully funded by a $13.13 million award from the US Department of War through its Peer-Reviewed Medical Research Program, which reduces BioVie's capital exposure at a stage when many small clinical-stage companies struggle for runway.
The candidate and its mechanism
Bezisterim is an investigational oral small molecule that crosses the blood-brain barrier and is proposed to reduce neuroinflammation by modulating the ERK, NFκB, and TNF-alpha pathways without broadly suppressing immune function. BioVie's hypothesis for Long COVID is that persistent circulation of spike protein fragments drives ongoing NFκB activation, producing the chronic neurological symptoms that affect a substantial proportion of those with the condition. According to Cuong Do, president and chief executive of BioVie, the growing body of Long COVID research continues to support that mechanistic rationale, particularly around inflammatory pathways linked to fatigue and cognitive difficulty.
Beyond Long COVID, bezisterim is being studied in Parkinson's disease and Alzheimer's disease. BioVie reported that its SUNRISE-PD proof-of-concept trial in early-stage, treatment-naive Parkinson's patients showed improvements in inflammation biomarkers and measures of daily functioning, motor symptoms, and non-motor symptoms relative to placebo. Preliminary data from Alzheimer's Phase 2 and Phase 3 trials also suggested cognitive and biomarker improvements, though BioVie has not presented full datasets for peer review in either indication.
Market context and competitive landscape
Long COVID represents one of the most significant unmet needs in post-infectious disease, with an estimated 17 to 20 million US adults reported to be living with the condition and around 3.8 million experiencing meaningful daily limitation. Despite that scale, the FDA has not approved any treatment specifically for Long COVID, leaving the field open for first-mover advantage.
The neuroinflammation hypothesis has attracted a range of academic groups and companies, including those pursuing antivirals, low-dose naltrexone protocols, and immune-modulating biologics. BioVie's anti-inflammatory small-molecule approach sits within a crowded mechanistic thesis but occupies a relatively distinct regulatory niche given the government-funded trial, which may lend the forthcoming dataset additional credibility with payers and regulators. MHRA and EMA have both signalled interest in Long COVID trial designs, and a positive Phase 2 readout could support further government-backed development in the UK and Europe.
Investors will scrutinise the topline data carefully. BioVie is a micro-cap listed on NASDAQ under the ticker BIVI, and the stock has historically been sensitive to clinical news. Whether the ADDRESS-LC results are sufficient to attract a larger partner or support an independent Phase 3 filing will depend on effect sizes across the composite endpoints, particularly the objective cognitive function measures, which are harder to move than patient-reported fatigue scores and carry more weight with regulators.