BioVie Highlighted ADDRESS-LC Phase 2 Trial Design Exploring Bezisterim for the Treatment of Neurological Symptoms of Long COVID at Keystone Symposia on Long COVID and Other Post-Acute Infection Syndromes
BioVie (NASDAQ: BIVI) presented the design of its Phase 2 ADDRESS-LC trial for bezisterim at the Keystone Symposia on Long COVID. The trial, fully funded by the U.S. Department of Defense, is evaluating bezisterim for treating cognitive impairment and fatigue in Long COVID patients.
The study features a 16-week, double-blind, randomized, placebo-controlled design with a novel enrichment strategy. Bezisterim, an anti-inflammatory agent that crosses the blood-brain barrier, has shown favorable safety profiles in Alzheimer's and Parkinson's disease trials.
The trial addresses a significant medical need, as Long COVID affects an estimated 400 million people worldwide, including 18 million in the United States. The study stratifies participants by symptom duration and age, using a specialized Cogstate Cognitive Battery to assess neurocognitive improvements.
BioVie (NASDAQ: BIVI) ha presentato il disegno del suo studio di Fase 2 ADDRESS-LC per bezisterim al Keystone Symposia on Long COVID. Lo studio, finanziato interamente dal Dipartimento della Difesa degli Stati Uniti, valuta bezisterim per il trattamento del deficit cognitivo e dell'affaticamento nei pazienti con Long COVID.
Lo studio prevede un disegno randomizzato, in doppio cieco, controllato con placebo della durata di 16 settimane con una strategia di arricchimento innovativa. Bezisterim, un agente antiinfiammatorio che attraversa la barriera emato-encefalica, ha mostrato profili di sicurezza favorevoli negli studi su Alzheimer e Parkinson.
Il trial risponde a un bisogno medico significativo, dato che il Long COVID interessa stimati 400 milioni di persone in tutto il mondo, comprese 18 milioni negli Stati Uniti. Lo studio stratifica i partecipanti in base alla durata dei sintomi e all'età, impiegando una specifica Cogstate Cognitive Battery per valutare i miglioramenti neurocognitivi.
BioVie (NASDAQ: BIVI) presentó el diseño de su ensayo de Fase 2 ADDRESS-LC para bezisterim en el Keystone Symposia on Long COVID. El ensayo, financiado íntegramente por el Departamento de Defensa de EE. UU., evalúa bezisterim para el tratamiento del deterioro cognitivo y la fatiga en pacientes con Long COVID.
El estudio incluye un diseño aleatorizado, doble ciego y controlado con placebo de 16 semanas con una estrategia de enriquecimiento novedosa. Bezisterim, un agente antiinflamatorio que atraviesa la barrera hematoencefálica, ha mostrado perfiles de seguridad favorables en ensayos sobre Alzheimer y Parkinson.
El ensayo aborda una necesidad médica importante, ya que el Long COVID afecta a unos 400 millones de personas en todo el mundo, incluidas 18 millones en Estados Unidos. El estudio estratifica a los participantes según la duración de los síntomas y la edad, utilizando una Cogstate Cognitive Battery especializada para evaluar las mejoras neurocognitivas.
BioVie (NASDAQ: BIVI)는 Keystone Symposia on Long COVID에서 bezisterim을 위한 2상 ADDRESS-LC 시험 설계안을 발표했습니다. 이 연구는 미 국방부의 전액 지원을 받아 Long COVID 환자의 인지 저하와 피로 치료에 대한 bezisterim의 효능을 평가합니다.
연구는 16주간의 무작위배정, 이중맹검, 위약대조 설계에 새로운 모집(enrichment) 전략을 결합한 방식으로 진행됩니다. 혈뇌장벽을 통과하는 항염증제인 bezisterim은 알츠하이머 및 파킨슨 병 임상에서 우호적인 안전성 프로필을 보였습니다.
이 임상은 중요한 의학적 수요를 다루고 있으며, Long COVID는 전 세계적으로 약 4억 명, 미국에서 약 1,800만 명이 겪고 있는 것으로 추정됩니다. 연구는 증상 지속 기간과 연령에 따라 참가자를 층화하고, 신경인지 개선을 평가하기 위해 특화된 Cogstate 인지 배터리를 사용합니다.
BioVie (NASDAQ: BIVI) a présenté la conception de son essai de phase 2 ADDRESS-LC pour le bezisterim lors du Keystone Symposia on Long COVID. L'essai, entièrement financé par le Département de la Défense des États-Unis, évalue le bezisterim pour le traitement des troubles cognitifs et de la fatigue chez les patients atteints de Long COVID.
L'étude comporte un schéma randomisé, en double aveugle et contrôlé par placebo de 16 semaines avec une stratégie d'enrichissement innovante. Le bezisterim, un agent anti-inflammatoire traversant la barrière hémato-encéphalique, a montré des profils de sécurité favorables dans des essais sur la maladie d'Alzheimer et la maladie de Parkinson.
Cet essai répond à un besoin médical important, car le Long COVID toucherait environ 400 millions de personnes dans le monde, dont 18 millions aux États-Unis. L'étude stratifie les participants selon la durée des symptômes et l'âge, en utilisant une batterie cognitive Cogstate spécialisée pour évaluer les améliorations neurocognitives.
BioVie (NASDAQ: BIVI) stellte auf dem Keystone Symposia on Long COVID das Design seiner Phase-2-Studie ADDRESS-LC für bezisterim vor. Die Studie, die vollständig vom US-Verteidigungsministerium finanziert wird, untersucht bezisterim zur Behandlung kognitiver Beeinträchtigungen und Fatigue bei Long-COVID-Patienten.
Die Studie sieht ein 16-wöchiges, randomisiertes, doppelblindes, placebokontrolliertes Design mit einer neuartigen Enrichment-Strategie vor. Bezisterim ist ein entzündungshemmender Wirkstoff, der die Blut-Hirn-Schranke passiert und in Studien zu Alzheimer und Parkinson günstige Sicherheitsprofile gezeigt hat.
Die Studie adressiert einen erheblichen medizinischen Bedarf: Long COVID betrifft schätzungsweise 400 Millionen Menschen weltweit, darunter 18 Millionen in den USA. Die Teilnehmer werden nach Symptondauer und Alter geschichtet, wobei eine spezielle Cogstate Cognitive Battery zur Bewertung neurokognitiver Verbesserungen eingesetzt wird.
- Trial is fully funded by U.S. Department of Defense grant
- Bezisterim has demonstrated favorable safety profile in previous trials
- Drug crosses blood-brain barrier and is orally available
- Addresses large market with 400 million affected patients worldwide
- No FDA-approved treatment options currently exist for Long COVID
- Long COVID symptoms can persist for years
- Complex patient stratification may impact trial enrollment speed
Insights
BioVie's Phase 2 trial for bezisterim in Long COVID shows promising scientific approach targeting neuroinflammation with DOD funding support.
BioVie is making notable progress with its ADDRESS-LC Phase 2 trial for bezisterim (NE3107) in treating neurological symptoms of Long COVID. This double-blind, randomized, placebo-controlled study is strategically designed with patient input and fully funded by the U.S. Department of Defense - a significant vote of confidence in the approach.
The trial's scientific foundation appears sound. Bezisterim targets neuroinflammation through dual mechanisms: inhibiting TLR4-induced signaling and inflammatory NF-κB signaling. This approach makes mechanistic sense for Long COVID, where persistent neuroinflammation has been documented in many patients. The drug's ability to cross the blood-brain barrier while being orally available and non-immunosuppressive represents an advantageous delivery profile.
The study design incorporates several sophisticated elements to enhance signal detection. Participants are enriched for cognitive impairment and fatigue - the primary neurological symptoms being targeted. The trial also stratifies by both symptom duration (<2 years or ≥2 years) and age (18-45 or 46-64), acknowledging the heterogeneity of Long COVID presentation. The primary endpoint utilizes a bespoke Cogstate Cognitive Battery, an objective measurement tool specifically designed for this population.
Previous clinical experience with bezisterim in Alzheimer's and Parkinson's disease has already demonstrated a favorable safety and tolerability profile, potentially streamlining the development pathway. While this is early-stage research, the trial addresses an enormous unmet need with an estimated 400 million individuals affected worldwide and no FDA-approved treatments for the neurological symptoms of Long COVID.
ADDRESS-LC trial is now enrolling patients with Long COVID-related fatigue and cognitive impairment at sites across the U.S.
CARSON CITY, Nev., Aug. 13, 2025 (GLOBE NEWSWIRE) -- BioVie Inc. (NASDAQ: BIVI) (“BioVie” or the “Company”), a clinical-stage company developing innovative drug therapies for neurological and neurodegenerative diseases, today announced that a poster highlighting the design and enrichment strategy of its ongoing Phase 2 ADDRESS-LC trial will be presented at the Keystone Symposia on Long COVID and Other Post-Acute Infection Syndromes, held August 10–13 in Santa Fe, New Mexico.
Long COVID is now recognized as a leading neurological condition that has affected an estimated 400 million individuals worldwide,1,2 .The Centers for Disease Control has reported that
Bezisterim is an anti-inflammatory agent being developed for Long COVID and other neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD), in which TLR-driven inflammation contributes to cognitive decline. It has been shown to inhibit both TLR4-induced signaling and inflammatory NF-κB signaling,4 and is orally available, not immunosuppressive, and crosses the blood-brain barrier.5,6 In clinical trials of AD and PD, bezisterim has demonstrated a favorable safety and tolerability profile.
"The ADDRESS-LC trial was designed with input from Long COVID patients with the goal of helping to address the tremendous unmet needs of this community," said Penelope Markham, PhD, Senior Vice President of BioVie’s Liver Disease and Long COVID Programs, who will be presenting the design. "Ongoing neuroinflammation has been observed in many patients with Long COVID, and BioVie leveraged its experience in studying other neurodegenerative diseases characterized by inflammation to create a unique trial that will both rigorously evaluate bezisterim in patients and add to our understanding of Long COVID pathology as a whole”.
The ADDRESS-LC trial features a novel design informed by direct input from clinicians and patients, incorporating pragmatic elements to enhance relevance and feasibility. The study employs an enrichment strategy to increase the likelihood of signal detection and stratifies participants by symptom duration (<2 years or ≥2 years) to account for potential development of refractory symptoms, as well as by age (18–45 or 46–64) to address age-related differences in cognition. Key endpoints include the change in performance on a bespoke Cogstate Cognitive Battery, an objective tool designed to assess bezisterim’s potential to improve neurocognitive symptoms such as cognitive impairment associated with Long COVID.
Details for the oral and poster presentations are as follows:
Oral Presentation and Poster Details:
Title: A Phase 2 Trial Designed to Enhance Signal Detection in an Evaluation of Bezisterim (NE3107) For the Treatment of Neurological Symptoms of Long COVID
Symposia Spotlight: 2:15pm-4:30pm (MT), Monday, August 11
Poster displayed from 7:30pm-10:00pm (MT), Tuesday August 12
Poster number: 2011
To learn more about ADDRESS-LC trial enrollment, visit www.addresslc.com.
About Bezisterim
Bezisterim (NE3107) is an orally bioavailable, blood-brain barrier (BBB)-permeable modulator of inflammation and insulin-sensitizer. In addition, it is not immunosuppressive and has a low risk of drug-drug interaction. By binding to ERK and selectively modulating NFκB activation and TNF-α production, BioVie believes that bezisterim may offer clinical improvements in several disease indications, including Alzheimer’s disease, Parkinson’s disease and long COVID.
In Parkinson’s disease, BioVie is currently enrolling patients in the Phase 2 SUNRISE-PD clinical trial evaluating the safety and efficacy of bezisterim on motor and non-motor symptoms in patients who have not been treated with carbidopa/levodopa, with topline data expected in late 2025 or early 2026. A previous Phase 2 study of bezisterim in Parkinson’s disease (NCT05083260) completed in 2022, and data presented at the AD/PD™ 2023 International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders in Gothenburg, Sweden in March 2023 showed significant improvements in “morning on” symptoms and clinically meaningful improvement in motor control in patients treated with a combination of bezisterim and levodopa versus patients treated with levodopa alone, and no drug-related adverse events.
In long COVID, bezisterim has the potential to reduce neurological symptoms including fatigue and cognitive dysfunction. Persistently circulating viral spike proteins are believed to trigger TLR-4 driven activation of NFκB and the subsequent expression of inflammatory cytokines (IL-6, TNF, IFNg). BioVIe’s Phase 2 ADDRESS-LC study, is a randomized (1:1), placebo-controlled, multicenter trial in approximately 200 patients to evaluate the safety, tolerability and potential efficacy of 3 months of treatment with bezisterim to reduce the neurocognitive symptoms associated with long COVID, including difficulty concentrating or remembering things (“brain fog”) and fatigue.
In Alzheimer’s disease, BioVie conducted and reported efficacy data on its Phase 3 randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate bezisterim in patients who have mild-to-moderate Alzheimer’s disease (NCT04669028) in 2023. Results of a Phase 2 investigator-initiated trial (NCT05227820) showing bezisterim-treated patients experienced improved cognition and biomarker levels were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) annual conference in December 2022. An estimated six million Americans suffer from Alzheimer’s disease.
Terms of the Department of Defense Award
The work is supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, by a fully funded award in the amount of
About BioVie Inc.
BioVie Inc. (NASDAQ: BIVI) is a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders (Alzheimer’s disease, Parkinson’s disease and long COVID) and advanced liver disease. In neurodegenerative disease, the Company’s drug candidate bezisterim inhibits inflammatory activation of extracellular signal-regulated kinase and the transcription factor nuclear factor-κB, and the associated neuroinflammation and insulin resistance but not ERK and NFκB homeostatic functions (e.g., insulin signaling and neuron growth and survival). Both neuroinflammation and insulin resistance are drivers of AD and PD. Persistent systematic inflammation and neuroinflammation are key features in patients with neurological symptoms of long COVID. In liver disease, the Company’s Orphan drug candidate BIV201 (continuous infusion terlipressin), with FDA Fast Track status, is being evaluated and discussed with guidance received from the FDA regarding the design of Phase 3 clinical testing of BIV201 for the reduction of further decompensation in participants with liver cirrhosis and ascites. The active agent is approved in the U.S. and in about 40 countries for related complications of advanced liver cirrhosis. For more information, visit www.bioviepharma.com.
Forward-Looking Statements
This press release contains forward-looking statements, which may be identified by words such as "expect," "look forward to," "anticipate" "intend," "plan," "believe," "seek," "estimate," "will," "project" or words of similar meaning. Although BioVie Inc. believes such forward-looking statements are based on reasonable assumptions, it can give no assurance that its expectations will be attained. Actual results may vary materially from those expressed or implied by the statements herein due to the Company's ability to successfully raise sufficient capital on reasonable terms or at all, available cash on hand and contractual and statutory limitations that could impair our ability to pay future dividends, our ability to complete our pre-clinical or clinical studies and to obtain approval for our product candidates, our ability to successfully defend potential future litigation, changes in local or national economic conditions as well as various additional risks, many of which are now unknown and generally out of the Company's control, and which are detailed from time to time in reports filed by the Company with the SEC, including quarterly reports on Form 10-Q, reports on Form 8-K and annual reports on Form 10-K. BioVie Inc. does not undertake any duty to update any statements contained herein (including any forward-looking statements), except as required by law.
REFERENCES
- Avitzur O. President's Column, 2022. American Academy of Neurology. Accessed June 16, 2025. https://www.aan.com/about-the-aan/presidents-column-advocating-post-acute-sequelae-covid
- Al-Aly Z, et al. Nat Med 2024;30:2148-2164. doi:10.1038/s41591-024-03173-6
- Ford ND, Agedew A, Dalton AF, Singleton J, Perrine CG, Saydah S. Notes from the Field: Long COVID Prevalence Among Adults — United States, 2022. MMWR Morb Mortal Wkly Rep 2024;73:135–136. DOI: http://dx.doi.org/10.15585/mmwr.mm7306a4.
- Davis HE, et al. EClinicalMedicine. 2021;38:101019. doi:10.1016/j.eclinm.2021.101019
- Reading CL, et al. Neurodegener Dis Manag. 2021;11(4):289-298. doi:10.2217/nmt-2021-0022
- Ahlem CN, et al. Int J Clin Exp Med. 2011;4(2):119-135.
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