BioVie Secures All Scientific Approvals Needed to Receive Additional $12.6 Million of Grant Funding to Launch Planned Phase 2 Trial to Evaluate Bezisterim in Long COVID

Rhea-AI Summary

BioVie Inc. (NASDAQ: BIVI) has secured all scientific approvals needed to receive an additional $12.6 million in grant funding from the U.S. Department of Defense for a planned Phase 2 trial of bezisterim in long COVID. The U.S. Army Medical Research and Development Command, Office of Human Research Oversight (OHRO) approved BioVie's plan to evaluate bezisterim for treating neurological symptoms associated with long COVID. This approval follows the FDA's Safe to Proceed designation in August 2024.

The Phase 2 study, expected to commence by early 2025, will be a randomized, placebo-controlled trial involving approximately 200 patients to assess the safety, tolerability, and potential efficacy of bezisterim in reducing neurocognitive symptoms of long COVID over a 3-month treatment period. Bezisterim, which can cross the blood-brain barrier, targets inflammation via NF-kB activation, addressing a suspected underlying cause of long COVID symptoms.

Positive

• Secured $12.6 million in additional grant funding from the U.S. Department of Defense
• Obtained all necessary scientific approvals for Phase 2 trial of bezisterim in long COVID
• FDA approved the study as Safe to Proceed in August 2024
• Phase 2 trial planned to commence by early 2025
• Bezisterim's mechanism of action targets a suspected underlying cause of long COVID symptoms

Negative

• None.

Approval from U.S. Army Medical Research and Development Command, Office of Human Research Oversight is the last scientific milestone needed for Company to receive
bulk of $13.1 million grant funding

Company anticipates Phase 2 trial to commence by early 2025

CARSON CITY, Nev., Sept. 16, 2024 (GLOBE NEWSWIRE) -- BioVie Inc. (NASDAQ: BIVI), (“BioVie” or the “Company”), a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease, today announced that the U.S. Army Medical Research and Development Command, Office of Human Research Oversight, (OHRO) has approved BioVie’s plan to evaluate bezisterim for the treatment of neurological symptoms that are associated with long COVID. FDA had previously reviewed and approved the study as Safe to Proceed in August 2024. Approval from OHRO is the last scientific review milestone needed for the Company to receive the additional $12.6 million in grant funding from the U.S. Department of Defense (DOD) and initiate Phase 2 testing in long COVID.

The planned Phase 2 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.

Long COVID is a condition in which symptoms of COVID-19, the acute respiratory disease caused by the SARS-CoV-2 virus, persist for an extended period of time, generally three months or more. The Centers for Disease Control recently reported that more than 17 million adults in the United States currently or previously had long COVID.¹ Symptoms include cognitive dysfunction and fatigue and are debilitating. No therapies have proven effective for treatment to date. Chronic inflammation is one of the main hypotheses that researchers have proposed to explain the persistence of symptoms in long COVID.³ Specifically in individuals with “brain fog,” sustained systemic inflammation and persistent localized blood-brain-barrier (BBB) dysfunction are key physiological features.⁵ Bezisterim permeates the BBB and has been shown to modulate inflammation via the activation of NF-kB, thus representing a novel oral treatment targeting a suspected underlying cause of long COVID symptoms.

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, in the amount of $499,200 for the planning phase with the option, if approved, to receive an additional $12.6 million, to initiate a clinical trial once the planning phase has concluded and milestones have been met, through the Peer-Reviewed Medical Research Program (PRMRP) under Award No. HT9425-24-1-0113. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Assistant Secretary of Defense for Health Affairs or the Department of Defense.

About Long COVID
Long COVID is a condition in which symptoms of COVID-19, the acute respiratory disease caused by the SARS-CoV-2 virus, persist for an extended period of time, generally three months or more. Common symptoms include lingering loss of smell and taste, hearing loss, extreme fatigue, and “brain fog,” though persistent cardiovascular and respiratory problems, muscle weakness, and neurologic issues have also been documented. The Centers for Disease Control recently reported that 6.8% of adults in the United States (more than 17 million individuals) currently or previously have long COVID.¹ The loss in quality of life and earnings and increased medical costs has an enormous economic impact estimated to be $3.7 trillion.² To date there are no non-pharmacological or pharmacological therapies proven effective for treatment of long COVID.

Chronic inflammation is one of the main hypotheses that researchers have proposed to explain the persistence of symptoms in long COVID.³ The expression of proteins associated with inflammation (LGALS9, CCL21, CCL22, TNF, CXCL10 and CD48) and immune regulation (IL1RN and CD22) have been shown to be elevated in individuals with long COVID versus full-recovered individuals.⁴ Specifically in individuals with “brain fog,” sustained systemic inflammation and persistent localized blood-brain-barrier (BBB) dysfunction are key physiological features.⁵ Thus, drugs modulating inflammation, and that work to regulate the BBB integrity, could represent potential therapeutic mechanisms for treating neurological symptoms of long COVID.

About Bezisterim
Bezisterim (NE3107) is an orally bioavailable, BBB-permeable, insulin-sensitizer that is also anti-inflammatory. In addition, it is not immunosuppressive and has a low risk of drug-drug interaction. Bezisterim has the potential to reduce symptoms of long COVID, including fatigue and cognitive dysfunction. Persistently circulating viral spike proteins are believed to trigger TLR-4 driven activation of NFkB and the subsequent expression of inflammatory cytokines (IL-6, TNF, IFNg). NE3107 has been shown to modulate the activation of NFkB and thus modulate inflammation.

Bezisterim is also being investigated for Alzheimer’s disease (“AD”) and Parkinson’s disease (“PD”). BioVie has 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 AD (NCT04669028). 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 AD. A Phase 2 study of bezisterim in PD (NCT05083260) has been completed, 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 vs. patients treated with levodopa alone, and no drug-related adverse events.

About BioVie Inc.
BioVie Inc. (NASDAQ: BIVI) is a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease. In neurodegenerative disease, the Company’s drug candidate bezisterim inhibits inflammatory activation of ERK and NFkB (e.g., TNF signaling) that leads to neuroinflammation and insulin resistance, but not their homeostatic functions (e.g., insulin signaling and neuron growth and survival). Both are drivers of AD and PD. 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 treatment of ascites due to chronic liver cirrhosis. 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
¹ 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.

² Cutler, David M. 2022 The economic costs of Long COVID: An update. long_covid_update_7-22.pdf (harvard.edu)

³ Evans RA, Leavy OC, Richardson M, et al. Clinical characteristics with inflammation profiling of Long-COVID and association with one-year recovery following hospitalisation in the UK: a prospective observational study. The Lancet Respiratory Medicine. 2022;10(8):761-775.

⁴ Yin K, Peluso MJ, Luo X, et al. Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2. Nature Immunology. 2024;25:218-225.

⁵ Greene C, Connoly R, Brennan D, et al. Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment. Nature Neuroscience. 2024;27:421-432.

For Investor Relations Inquiries:
Bruce Mackle
Managing Director, LifeSci Advisors, LLC
bmackle@lifesciadvisors.com

For Media Relations Inquiries:
Melyssa Weible
Managing Partner, Elixir Health Public Relations
mweible@elixirhealthpr.com

FAQ

What is the purpose of BioVie's planned Phase 2 trial for bezisterim (BIVI)?

The Phase 2 trial aims to evaluate the safety, tolerability, and potential efficacy of bezisterim in reducing neurocognitive symptoms associated with long COVID over a 3-month treatment period.

How much grant funding did BioVie (BIVI) secure for the bezisterim long COVID trial?

BioVie secured an additional $12.6 million in grant funding from the U.S. Department of Defense for the planned Phase 2 trial of bezisterim in long COVID.

When is BioVie (BIVI) expected to start the Phase 2 trial for bezisterim in long COVID?

BioVie anticipates the Phase 2 trial for bezisterim in long COVID to commence by early 2025.

How many patients will be involved in BioVie's (BIVI) Phase 2 trial for bezisterim in long COVID?

The planned Phase 2 study will involve approximately 200 patients in a randomized, placebo-controlled, multicenter trial.