Full Press Release Details
Issues Letter to Shareholders
City, NV, October 4, 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 issued the following letter shareholders:
are very excited about the data from an exploratory study we supported and hope that it will set the stage for what we may see in the
Phase 3 trial for NE3107 in mild- to moderate-Alzheimer's Disease (AD) patients that should read out in mid-2023. Thus, I've
prepared this shareholders' letter to explain our excitement and to provide updates on our other programs.
short, the preliminary data from this study suggests that 82% of MCI and mild AD patients treated with NE3107 over 3 months improved
their cognition (as measured by a modified ADAS-Cog12 score). The mean improvement was -2.6 points (p=0.0046) for all MCI and mild AD
patients and -3.5 points (p=0.0004) among the 82% responders. We believe these results, and in particular this level of improvement,
confirm NE3107's status as one of the most promising agents in development for AD.
company financially supported and supplied drug product for an Investigator-Sponsored Phase 2 exploratory biomarker study led by Dr.
Sheldon Jordan, founder of the Regenesis Project, to explore NE3107's impact on inflammation and insulin resistance and how it
may affect other biomarkers of interest to the AD research community. NE3107 was administered by an expert neurologist in a "real
world" clinical setting to individuals with documented ongoing memory deficits despite medical intervention. This study has been
completed, and initial topline results have been released.
has always held - and the data from thousands of publications suggest - that Alzheimer's disease pathology is driven
by multiple factors. The AD research community has focused on Amyloid Beta (A ) and phospho-tau (p-tau) for decades, but few A and p-tau
agents have been shown to have significant impact on cognition. We believe that focusing on any single factor such as A and p-tau is
insufficient, and that dysregulation in the AD brain is driven by inflammation, insulin resistance, metabolic dyshomeostasis, oxidative
stress, and other factors in addition to A and p-tau. The common thread among all these factors is neuroinflammation,
which is initiated by TNF . Preclinical and clinical trials have shown that NE3107 modulates the production of TNF - the major
regulator of inflammation - and reduces insulin resistance. This recently completed exploratory biomarker study provides the first
glimpse into how the reduction of inflammation and insulin resistance correlates with improvements in cognition, blood flow and metabolism
in the brain for some patients, and A and p-tau.
may recall that NE3107 was first brought to the clinic as an anti-inflammatory type 2 diabetes treatment. Phase 1 and 2 trials showed
that NE3107 decreased insulin resistance, postprandial glucose and HbA1c compared to placebo - a profile you would want for a potential
diabetes drug. Interestingly, patients treated with NE3107 also saw decreased systems dysregulation of inflammatory, hematopoietic and
metabolic parameters compared to placebo. Subsequently, others published that this type of inflammation-driven systems dysregulation
that NE3107 modulated is associated with Alzheimer's. Since NE3107's mechanism of action (MOA) was not fully understood at
the time, we couldn't fully explain why this was observed. Lastly, treated patients showed no differences in adverse events compared
to placebo, suggestive of an acceptable safety profile.
additional research, we came to learn that NE3107 has a very unique and unexpected MOA. It turns out that NE3107 modulates the activation
of the extracellular regulated kinase (ERK) into its active form (called p-ERK), thereby interfering with p-ERK's activation
of inflammatory nuclear factor kappa B (NF B). Reduced activation of NF B leads to the reduced production of TNF . Once our team figured
out NE3107's MOA, we realized that NE3107 potentially plays a critical role in modulating the inflammatory process at a critical
juncture right before the production of TNF and thus has the potential to disrupt the proinflammatory cascade in AD and dementia. With
this understanding, the company pivoted from diabetes to Alzheimer's.
recently completed open label trial enrolled 23 patients - 17 of whom are considered to have mild cognitive impairment or mild
Alzheimer's while 6 have moderate AD as measured by their Mini Mental State Examination (MMSE) score. The trial used advanced imaging
techniques and examined cerebrospinal fluid and blood biomarkers to compare what happened to patients before and after 3 months of treatment
with NE3107. I must stress this is a small open label study, thus it cannot detect the magnitude of the placebo effect as a double-blinded,
placebo-controlled trial could. But we are encouraged by the totality of the preliminary data and summarize the findings below.
are encouraged by the data showing that 82% of MCI and mild AD patients had improvements in their modified ADAS-Cog12 score, with a mean
improvement of -2.6 points (p=0.0046) or roughly 25% improvement from baseline (p=0.0026). Among this group of the 82% responders, the
mean improvement was -3.5 points (p=0.0004) on the ADAS-Cog12 scale. An improvement is represented by a lower disease score while a decline
is represented by a higher score.
it is difficult to make direct comparisons between NE3107's impact on ADAS-Cog to other agents due to differing study designs,
treatment durations and patient populations, the proportion of responders and level of improvements seen for NE3107 in this trial demonstrate
that NE3107 shows great potential. For some perspective, below are summaries of the results of the most recent clinical studies for Alzheimer's
additional randomized, controlled studies are required to draw clinically meaningful conclusions, when the data is taken in its totality,
it suggests that certain changes may be taking place in the brain that are consistent with NE3107's mechanism of action
and are unlikely to be accounted for by placebo effects.
of this gives us encouraging signs of what we will hopefully see from our Phase 3 in AD that is expected to read out mid-2023.
can watch and download the full presentation of the initial findings at: https://bioviepharma.com/topline-results/. Further hypothesis
testing and data analysis continue, and all findings will be presented by the Principal Investigator and his team at the Clinical
Trial in Alzheimer's Disease (CTAD) annual conference, to be held in San Francisco, CA November 29-December 2, 2022
also have three other trials underway that should read out over the next 12 months:
we are very excited with the progress of our clinical programs and the progress towards the potential of advancing meaningful therapies
for our patient communities. We expect to provide two significant data updates later this year: 1) the full data presentations from the
investigator-sponsored exploratory biomarker study at CTAD; and 2) topline data readout from the Parkinson's Phase 2 before year-end.
We are also looking forward to an exciting 2023 as we finalize the Alzheimer's Phase 3 and the ascites Phase 2b, both of which
are expected roughly mid-year.
hope you share our enthusiasm for how the programs are advancing and the potential for exciting catalysts over the next year. We thank
you for your support.
& Chief Executive Officer
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 of 2022. In liver disease, the Company's Orphan drug candidate BIV201 (continuous infusion
terlipressin), with FDA Fast Track status, is being evaluated in a US Phase 2b study for the treatment of refractory ascites due to liver
cirrhosis with top-line results anticipated in mid-2023. BIV201 is administered as a patent-pending liquid formulation. The active agent
is approved in about 40 countries for related complications of advanced liver cirrhosis but is not available in the US or Japan. For
more information, visit http://www.bioviepharma.com/.
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, 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.
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