BioVie Announces EfficacyData from Phase 3 Trial of NE3107 in Patientswith Mild to Moderate Alzheimer's Disease Positive TrendingData from 57 Per-Protocol PatientsSuggest NE3107 is Biologically Active and May Have Impact

BioVie Announces EfficacyData from Phase 3 Trial

in Patientswith Mild to Moderate Alzheimer's Disease

Positive TrendingData from 57 Per-Protocol PatientsSuggest

NE3107 is Biologically Active

and May Have Impact on Cognitive, Functional, and Biomarker Endpoints

Sponsor Identified Issues Relating to SignificantGCPViolations

and Protocol Deviations, Which Allowed for Data from Only a Subset of Enrolled Patients tobe Included in the Efficacy Analysis;Sites Suspectedof

Improprieties Have BeenReferred to FDA

Due to Exclusions, the Primary Efficacy EndpointMissedStatistical

Significance;Adaptive Feature of Trial May Allow the Company to Continue Enrolling Patients to Reach Statistical Significancefor Registrational

Management to Host Conference Call at 8:30 AMET

Today to Discuss Data

Carson City NV,November 29,- 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 positiveanalysisofunblinded,topline

efficacy data from its Phase 3 clinical trial (NCT04669028) of NE3107 in

the treatment of mild to moderate Alzheimer's Disease (AD).

Data from evaluable patients show NE3107's

treatment advantage compared to placebo may be equal to or greater than the benefit from approved AD monoclonal antibodies. NE3107-treated

patients also experienced a 4.66-year advantage in age deceleration vs. placebo as measured by epigenetics/DNA methylation Skin Blood

The trial started during the COVID-19 pandemic when

access to clinical sites was limited and enrolled a total of 439 patients through 39 sites. Upon trial completion, the Company found significant

deviation from protocol and Good Clinical Practice (GCP) violations at 15 sites (virtually all of which were from one geographic area).

This highly unusual level of suspected improprieties led the Companyto exclude all patients from these sites and to refer them to the

U.S. Food and Drug Administration(FDA) Office of Scientific Investigations (OSI) for further action. After these exclusions,81 patientsremained

in our Modified Intent to Treat (MITT) population, 57 of whom were in the Per-Protocol populationwhich included those who completed the

trial and wereverified to take study drug from pharmacokinetic(PK) data.

"These data show NE3107's treatment

advantage over placebo to potentially be equal to or greater than data reported from clinical trials for the approved medications

for AD without the associated safety concerns," said Cuong Do, BioVie's President and CEO. "The adaptive trial

design givesus the flexibility to continue patient enrollmentin the advancement of this potentially important treatment for AD, and

we look forward to discussing our findingsof NE3107's magnitude of therapeutic impact with our potentialpartners. I am also

very proud of the integrity our team displayed in taking immediate action to identify and report the potentially problematic sites

to the FDA for independent investigation.Importantly,we recognize that along with the development of new and innovative

therapeutics, our foremost responsibility in clinical testing is to protect the rights and well-being of study patients and the

integrity of the clinical research process."

"The unblinded topline efficacy data from

57 per-protocol participants reaffirmed what has been seen in previous studies of NE3107 - which is that patients treated with

this molecule appear to experience cognitive and functional improvements as measured by multiple assessment tools," said Dr.

Joseph Palumbo, Executive Vice President, R&D and Chief Medical Officer. "This data reinvigorates our ambition to further

evaluate NE3107 and bring the Alzheimer's community a differentiated treatment that is safe and has a meaningful impact on

"The unblinding of topline efficacy data from

the trialconfirmed an unusualpattern we saw with the blinded data - that patients in a particular demographic group within the trial

seemed tohave a data pattern different from historical evidence forthis demographic group.Patients from this demographic group in this

trialreportedly experienced cognitive improvements that were improbable scientifically, and inconsistent with the pathology of this disease,"

stated Suzanne Hendrix, Founder & CEO of Pentara, a specialized biostatistics consulting firm that has assisted dozens of AD clinical

trials. "When sensitivity analyses were performed, we determined that the anomalous demographic datawere associated with the previously

identified anomalous sites located in the same geographic area."

Conference Call & Webcast

The NCT04669028 Trial - Background &

The NCT04669028 trial is a Phase 3, double-blind,

randomized, placebo-controlled, parallel group, multicenter study of NE3107 in patients who have probable mild- to moderate-AD withscores

on CDR 1-2 and MMSE 14-24. The study has co-primary endpoints looking at cognition using the Alzheimer's Disease Assessment Scale-Cognitive

Scale (ADAS-Cog 12) and function using theClinical Dementia Rating-Sum of Boxes (CDR-SB). Patients went through two weeks each of 5 mg

and 10 mg BID dose titration followed by 26 weeks of 20 mg twice daily vs. placebo, randomized 1:1.

The trial started enrolling patients in August 2021when COVID-19 pandemic

restrictions provided limited access to clinical sites,and the last patient's last treatment visit was completed in September 2023.

A total of 439 patientswere enrolled in the trial. BioVie monitored blinded data over the course of the trial to tracksafety and ensure

timely entry of data from the clinical sites into the Electronic Data Capture (EDC, the official database that is submitted to the FDA

for registrational purposes) by the Company's Clinical Research Organization (CRO). The CRO manages the EDC, and each clinical site

can enter data only from its patientswhile BioVie has read-only access to review blinded data.

Data Review and Audit

The Company retained three independent biostatistical consulting

firms to analyze the data, including Pentara, which has helped pharmaceutical companies assess dozens of AD trials. Pentara reviewed

the blinded data when enough patients completed the trial and identified: 1) several sites in a singlegeographic area were anomalous

(inconsistent data patterns compared to historical data, large proportions of patientsimproving compared to baseline, unusual data

variability); and 2) all patientsin a particular demographic group enrolled in this trial seemed to havea data pattern not

explainable based on established disease progression and which substantially deviated from historical data for this demographic in

other AD trials. Without unblinding and PK data, there was no way to identify the causeof the pattern. Thus,Pentara recommended a

subgroup analysis of the identified demographic group vs.all others and anomalous sites vs. others when the study becomes

In parallel, some sites started to complete their patient-facing activities

in early summer 2023, which created the first opportunity for BioVie to start the data verification and assessment process. The processsurfaced

unusual data patterns and deviations from expectations (missing data, suspectedcopied/pasted MRI results, etc.), which ledthe Company

to retain two new CROsto conduct a multi-step process that entailed quality control (QC) visits at all sites, performingsource data verification

(SDV) on 100% of the documents used in the clinical sites to ensure what was notated on paper during patient visits was accurately reflected

in the EDC, and auditing the sites. This extensive, multi-monthprocess concluded when the Company received the final report identifying

six sites that appeared to havea large number ofdeviations from the study protocol and Good Clinical Practices (GCP).

Based on the reportedfindings, and to act responsibly with an abundance

of caution, the Company undertook the following before the EDC containing cognitive and functional assessments from the clinical sites

As the top-line efficacy data was unblinded and PK data became available,

the pre-specified demographic subgroup analyses showed that patients in the identified demographic on placebo significantly improved cognitively

without any intervention - a finding that cannot be explained scientifically. Furthermore, the pre-specified anomalous sites vs.

others revealed a similar scientifically improbable and that these 9 sites are in the same single geographic area.It turned out that virtually

all of the patients in the identified demographic group were associated with the 9 anomalous sites. Consistent with our pre-specified

statistical plan, these 9 additional sites were also excluded to arrive at our Modified Intent to Treat population, which became underpowered

with just 81 subjects. Out of an abundance of caution, we also referred these 9 additional sites to the FDA's OSI. It should be

noted that virtually all of the 15sites referred to the FDA were in the same geographic area.

= Clinical Dementia Rating-Sum of Boxes;ADAS-Cog12 = Alzheimer's Disease Assessment Scale-Cognitive

Adaptive Design & Next Steps

The trial was originally designed to be 80% powered with 125 patients

in each of the treatment and placebo arms. The unplanned exclusion of so many patients has left the trial unpowered for the primary endpoints.

Based on the efficacy signal seen in this trial, the Company intends to work with the FDA to potentially employ the adaptive trial feature

of the protocol to continue enrolling patients to achieve statistical significance. The Company has retained a new CRO for future trials.

NE3107 is an oral, small molecule, blood-brain permeable

anti-inflammatory insulin sensitizer that binds extracellular signal-regulated kinase.BioVie's Phase 3 trial is the largest study

to date to evaluate the safety and efficacy of NE3107 in patients with AD. NE3107 is the only anti-inflammatory agent currently in phase

3 development for AD. Consistent with the proposed anti-inflammatory and insulin-sensitizing properties of NE3107, this phase 3 study

was designed to confirm the efficacy and safety of NE3107 treatment in patients with probable AD.

BioVie Inc. (NASDAQ: BIVI) is a clinical-stage company