Full Press Release Details
BioVie and Dr. Sheldon Jordan Jointly Announce
Topline Results from an
Investigator-Sponsored Exploratory Biomarker and Imaging Trial of NE3107 for
the Treatment of Alzheimer's
BioVie Provides Updates on Other Clinical Programs
Carson City, NV, September 7, 2022 -
BioVie Inc., (NASDAQ: BIVI) ("BioVie" or the "Company") a clinical-stage company developing innovative drug therapies
for the treatment of advanced liver disease and neurological and neurodegenerative disorders, today announced topline results from an
investigator-Sponsored Phase 2 clinical trial of NE3107 for the treatment of Alzheimer's Disease (AD). Updates from other trials
underway are also provided.
AD research has largely focused on Amyloid Beta (A )
and phospho-tau (p-tau) for decades and has resulted in a large number of trials targeting these mechanisms.1
More recently, however, research focus has shifted towards targeting neuroinflammation, as evidenced by the 23 disease-modifying agents
listed in clinicaltrials.gov in 2021 investigating inflammation or the immune system. NE3107 is the only molecule in this group that is
pursuing a two-pronged approach targeting both neuroinflammation and insulin resistance. Furthermore, NE3107 is the only molecule in the
group that is conducting a potentially pivotal Phase 3 trial (NCT04669028) that is currently underway in mild- to moderate-AD patients
with co-primary endpoints of cognition, as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12),
and function, as measured by Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), whereas 17
other agents are in Phase 2. This Phase 3 trial is expected to provide topline results in mid-2023.
Tumor Necrosis Factor Alpha (TNF ) is a cytokine identified
as a major regulator of inflammation given that its excessive activation is associated with chronic inflammation.2
It is considered to be the central mediator of inflammation due to its role at the top of the biochemical pathway that leads to the production
of other inflammatory factors such as various cytokines (e.g., IFN , IL-1 , IL23, IL-4, IL-17), neurotoxic A peptide oligomers,
activation of IKK and JNK (that leads to insulin resistance), and others. A large retrospective study analyzing the electronic medical
records of 56 million unique patients demonstrated the linkage between TNF and AD by showing that patients with rheumatoid arthritis
and psoriasis taking TNF blocking agents had significantly lower AD risk.3
Preclinical studies showed NE3107 is a modulator of TNF production through its ability to modulate the activation of the Extracellular
Regulated Kinase (ERK) and Nuclear Factor kappa B (NF B).4
By down regulating the activation of ERK and NF B, NE3107 has been shown to reduce the production of TNF .5
The Company's newly generated data supporting a new patent application show that NE3107 inhibits inflammatory ERK activation and
blocks the phosphorylation of TNF receptor 1 (TNFR1) in an IKK-MAP3K8-MEK dependent pathway to decrease forward-feeding TNF inflammatory
cascades, thereby lowering the expression of other downstream inflammatory factors.
Since the NE3107 Phase 3 trial underway is focused
on cognition and function and is not focused on collecting neuroinflammatory biomarkers, the Company supported a Phase 2 investigator-initiated
trial (NCT05227820) to explore the link between NE3107's role in neuroinflammation and insulin resistance to the biomarkers historically
used by the AD research community. It also was designed to provide, if possible, a glimpse into what can be expected regarding cognition
and function when the Phase 3 trial reads out next year. This was done by using a modified ADAS-Cog12 scale for cognition and the Global
Rating of Change (GRoC), which is an instrument that can be administered more easily in general clinical practices than the ADCS-CGIC.
The Phase 2 trial- A Phase II Open-Label
Study for the Use of Anti-Inflammatory, Insulin-Sensitizing NE3107 for Treatment of Cognitive Decline Due to Degenerative Dementias (NCT05227820)
- is an exploratory biomarker study conducted by Dr. Sheldon Jordan6,
who served as principal investigator for the trial. The trial was intended to explore NE3107's potential role in real-world clinical
practice as an exploratory precursor informing the design of subsequent placebo-controlled blinded studies.
Results from Phase 2 Exploratory Biomarker Trial
The trial enrolled a total of 23 patients -
17 patients with Mini-Mental State Examination (MMSE) scores greater than or equal to 20 (i.e., mild cognitive impairment [MCI] to mild
AD) and 6 patients with MMSE <20 (i.e., moderate AD) - in an open-label, single arm study. The trial measured changes in cognition
through verbal and visual test procedures, changes in biomarkers of Alzheimer's disease and inflammation that can be measured in
cerebral spinal fluid (CSF) and serum samples, and with functional magnetic resonance imaging techniques in patients before and after
treatment with 20 mg of NE3107 twice daily for 3 months.
Initial results showed that the measurements for most
patients improved with NE3107 treatment, although MCI/mild AD patients showed greater change.
The Company will present the final data and statistical
analyses, which may deviate from the initial result presented here, at the Clinical Trial in Alzheimer's Disease (CTAD) annual
conference, to be held in San Francisco, CA November 29-December 2, 2022. Platform presentations and posters will provide detailed findings
on changes on biomarker, neuropsychological assessments, and advanced MRI imaging. Research papers are being prepared to present the findings
and will be submitted to peer-reviewed journals for publication.
"Through our work, we are seeking to deepen
our understanding of brain degeneration and ultimately identify promising treatments that have the potential to counteract the degenerative
process. Results from this trial provide encouraging signals that NE3107 may offer significant potential to reduce neuroinflammation and
potentially improve metabolic parameters such as glutathione in the brain, and warrant further study in this patient population,"
said Dr. Jordan. "I was surprised to see imaging data changes and how so many patients had increased GRoC score, indicating they
can perform more activities of daily living."
"We are delighted to support the work of Dr.
Jordan and his team and are very pleased to have this initial data-driven validation of NE3107's potential role for the treatment
of people suffering from cognitive impairment and dementia," stated Dr. Joseph Palumbo, BioVie's Chief Medical Officer. "Despite
this being an open label study, the insights provided are instructional and directionally very interesting. While it is not possible to
isolate the placebo effect in an open label study as a placebo-controlled double blinded trial can, results on TPO arterial spin label
imaging, hippocampal blood oxygen level-dependent imaging, brain NMR spectroscopy measuring glutathione, and peripheral TNF reduction
from this study provide helpful information to plan our next steps."
"This study provides us with an early opportunity
to assess the effects of NE3107's mechanism of action in the brain, and these topline results represent the first detailed data
linking NE3107's role in neuroinflammation and insulin resistance with the traditional biomarkers of interest to the AD research
community," added Cuong V. Do, President and CEO of BioVie. "I was excited about correlation of TNF reduction with improvements
in cognition and how treated patients saw an improvement in the ratio of p-tau:A . We supported Dr. Jordan's Investigator-Sponsored
trial as an exploratory biomarker study to guide our efforts to design future placebo-controlled trials to examine the potential impact
of NE3107 on traditional AD biomarkers and measures of cognition and function. We are very grateful for the work of Dr. Jordan and his
team on this important study and look forward to the team's presentation at CTAD later this year."
Commenting on the mixed results observed in AD research
over the decades, Mr. Do added, "AD drug development at BioVie is based on the evidence that AD pathology is multifactorial in nature.
While A and p-tau are important factors, decades of research on dozens of agents have not conclusively correlated improvements on these
individual factors to improvements in cognition. We believe additional factors such as inflammation, insulin resistance, metabolic dyshomeostasis,
apoptosis, oxidative stress, and glucose utilization also play critical roles in AD etiology. Data shows that NE3107's ability to
reduce TNF (the major regulator of inflammation) is highly correlated to improvements in cognition. We are pleased that the Principal
Investigator observed these changes in 23 patients in only 3 months. We hypothesize that the modulation of TNF levels and its inflammatory
activation via TNFR1 lead to a multitude of changes among the many factors downstream from this master regulator, which collectively lead
to improvements in neuronal health and cognition."
Update on other clinal trials
In addition to the Phase 2 exploratory biomarker trial, the Company has
three other trials underway.
The updated corporate overview and additional information can be found
BioVie Inc. (NASDAQ: BIVI) is a clinical-stage
company developing innovative therapies to overcome unmet medical needs in chronic debilitating conditions. In neurodegenerative disease,
the Company's drug candidate NE3107 inhibits inflammatory activation of ERK and NF B (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 Alzheimer's and Parkinson's diseases. The Company is conducting a potentially pivotal Phase 3 randomized, double blind,
placebo controlled, parallel group, multicenter study to evaluate NE3107 in patients who have mild to moderate Alzheimer's disease
(NCT04669028) and is targeting primary completion in mid-2023. An estimated six million Americans suffer from Alzheimer's. A Phase
2 study of NE3107 in Parkinson's disease (NCT05083260) is enrolling patients and expects to have topline data readout by the end