UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
(Mark One)
☒ANNUAL REPORT UNDER SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934.
FOR THE FISCAL YEAR ENDED JUNE 30, 2026
☐TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from ____________to _____________
Commission File Number: 001-39015
BIOVIE INC.
(Exact name of registrant as specified in its
charter)
(Address of principal executive offices, Zip Code)
(Registrant’s telephone number, including area code)
Securities registered pursuant to Section 12(b)
of the Act:
Title of each class Trading Symbol(s) Name of each exchange on which registered
Securities registered pursuant to Section 12(g)
of the Act:
None
Indicate by check mark if the registrant is a
well-known seasoned issuer, as defined in Rule 405 of the Securities Act.
Yes ☐No☒
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required to file reports pursuant to Section 13 or Section 15(d) of the Act
Yes ☐No☒
Indicate by check mark whether the registrant
(1) has filed all reports required to be filed by Section 13 or 15(d) of the Exchange Act during the past 12 months (or for such shorter
period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.
Yes☒
No ☐
Indicate by check mark whether the registrant
has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405
of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).
Yes☒
No ☐
Indicate by check mark whether the registrant
is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company.
See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,”
and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large Accelerated Filer ☐ Accelerated Filer ☐
Non-Accelerated Filer ☒ Smaller reporting company ☒
Emerging growth company ☐
If an emerging growth company, indicate by check
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standards provided pursuant to Section 13(a) of the Exchange Act. ☐
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under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7362(b)) by the registered public accounting firm that prepared or issued its
audit report.
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If securities are registered pursuant to Section
12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction
of an error to previously issued financial statements. ☐
Indicate by check mark whether any of those error
corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s
executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate by check mark whether the registrant
is a shell company (as defined in Rule 12b-2 of the Exchange Act).
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The aggregate market value of the voting and non-voting
common equity held by non-affiliates computed by reference to the price at which the common equity was last sold, or the average bid and
asked price of such common equity, as of the last business day of the registrant’s most recently completed second fiscal quarter
was $8,454,444.
There were 7,542,638 shares of the Registrant’s
Class A Common Stock, $0.0001 par value per share, outstanding as of August 10, 2026.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the Registrant’s definitive proxy statement relating
to its 2026 annual meeting of stockholders (the “2026 Proxy Statement”) are incorporated by reference into Part III of this
Annual Report on Form 10-K where indicated.
BIOVIE INC.
FORM 10-K INDEX
PART I
Item 1. Business 1
Item 1A. Risk Factors 11
Item 1B. Unresolved Staff Comments 37
Item 1C. Cybersecurity 37
Item 2. Properties 38
Item 3. Legal Proceedings 38
Item 4. Mine Safety Disclosures 39
PART II
Item 6. [Reserved] 40
Item 7A. Quantitative and Qualitative Disclosures About Market Risk 45
Item 8. Financial Statements and Supplementary Data 45
Item 9A Controls and Procedures 46
Item 9B. Other Information 46
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 46
PART III
Item 10. Directors, Executive Officers and Corporate Governance 47
Item 11. Executive Compensation 47
Item 14. Principal Accountant Fees and Services 47
PART IV
Item 15. Exhibits and Financial Statement Schedules 48
BIOVIE INC.
FORWARD-LOOKING STATEMENTS
This Annual Report on Form 10-K (this “report”)
contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934 as amended (the “Exchange
Act”), and Section 27A of the Securities Act of 1933, as amended (the “Securities Act”). Any statements contained in
this report that are not statements of historical fact may be forward-looking statements. When we use the words “intends,”
“estimates,” “predicts,” “potential,” “continues,” “anticipates,” “plans,”
“expects,” “believes,” “should,” “could,” “may,” “will” or the
negative of these terms or other comparable terminology, we are identifying forward-looking statements. Forward-looking statements involve
risks and uncertainties, which may cause our actual results, performance or achievements to be materially different from those expressed
or implied by forward-looking statements. These factors include our research and development activities, distributor channel; compliance
with regulatory impositions; and our capital needs. Although we believe that the expectations reflected in the forward-looking statements
are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.
Except as may be required by applicable law, we
do not undertake or intend to update or revise our forward-looking statements, and we assume no obligation to update any forward-looking
statements contained in this report as a result of new information or future events or developments. Thus, you should not assume that
our silence over time means that actual events are bearing out as expressed or implied in such forward-looking statements. You should
carefully review and consider the various disclosures we make in this report and our other reports filed with the Securities and Exchange
Commission (the “Commission”) that attempt to advise interested parties of the risks, uncertainties and other factors that
may affect our business.
When used in this report, the terms “BioVie”,
“Company”, “we”, “our”, and “us” refer to BioVie Inc.
PART I
ITEM 1. BUSINESS
Overview
BioVie Inc. (the “Company” or “we”
or “our”) is a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative
disorders and advanced liver disease.
Neurodegenerative Disease Programs
The Company acquired the biopharmaceutical assets
of NeurMedix, Inc. (“NeurMedix”) a privately held clinical-stage pharmaceutical company and a related party in June 2021.
The acquired assets included NE3107 (“bezisterim”). Bezisterim, the approved generic name for NE3107 is an investigational,
novel, orally administered small molecule that is thought to inhibit inflammation-driven insulin resistance and major pathological inflammatory
cascades with a novel mechanism of action. There is emerging scientific consensus that both inflammation and insulin resistance may play
fundamental roles in the development of Alzheimer’s disease (“AD”) and Parkinson’s disease (“PD”),
and bezisterim could, if approved by the U.S. Food and Drug Administration (“FDA”), represent an entirely new medical approach
to treating these devastating conditions affecting an estimated 6 million Americans suffering from AD, 1 million Americans suffering from
PD, and approximately 20 million adults in the US suffering from Long COVID, with millions more affected worldwide.
With respect to the mechanism of action, we believe
bezisterim inhibits activation of inflammatory extracellular signal-regulated kinase (“ERK”) and nuclear factor kappa-light-chain-enhancer
of activated B cells (“NFκB”) (including interactions with tumor necrosis factor (“TNF”) signaling and other
relevant inflammatory pathways) that lead to neuroinflammation and insulin resistance. By binding to ERK and selectively modulating NFκB
activation and TNF-α production without interfering with their homeostatic functions (e.g., insulin signaling and neuron growth
and survival), we believe that bezisterim may offer clinical improvements in several disease indications, including PD, AD and long COVID.
Chronic neuroinflammation, insulin resistance,
and oxidative stress are common features in the major neurodegenerative diseases, including AD, PD, frontotemporal lobar dementia, and
Amyotrophic lateral sclerosis. Bezisterim (NE3107) is an investigational oral small molecule, blood-brain permeable, compound with potential
anti-inflammatory, insulin sensitizing, and ERK-binding properties that may allow it to selectively inhibit ERK-, NFκB- and TNF-stimulated
inflammation. Bezisterim’s (NE3107) potential to inhibit neuroinflammation and insulin resistance forms the basis for the Company’s
work testing the molecule in AD, PD, and long COVID patients. Bezisterim (NE3107) is patented in the United States, Australia, Canada,
Europe and South Korea.
Parkinson’s Disease
PD is driven in large part by neuroinflammation
and activation of brain microglia, leading to increased proinflammatory cytokines (particularly TNF). Multiple daily administrations of
levodopa (converted to dopamine in the brain) is the current standard of care treatment for this movement disorder. However, levodopa
effectiveness diminishes over time necessitating increased dosage and prolonged daily administration leads to side effects of uncontrolled
movements called levodopa-induced dyskinesia, commonly referred to as LID, which is exacerbated by high dose levodopa. Although levodopa
provides symptomatic benefit, it does not slow PD progression.
In August 2026, we
announced topline results from our Phase 2b SUNRISE-PD clinical trial (NCT06757010), a multicenter, randomized, double-blind, placebo-controlled
study evaluating bezisterim (20 mg twice daily) in 57 patients with early-stage PD who were naïve to symptomatic dopaminergic therapy
(carbidopa/levodopa). The trial was designed to establish proof-of-mechanism and proof-of-concept for bezisterim in this patient population
and to inform the design of a potentially pivotal Phase 3 registrational trial. Over a 12-week treatment period, the study prospectively
evaluated a predefined battery of biologic, clinical, and quality of life assessments to examine motor and non-motor endpoints consistent
with bezisterim’s expected metabolic and anti-inflammatory actions.
1
The trial’s primary pharmacodynamic endpoint assessed
the effect of bezisterim on hematologic inflammatory biomarker indices, specifically the monocyte-to-lymphocyte ratio (MLR), Systemic
Inflammation Response Index (SIRI), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte
ratio (PLR), and aggregate index of systemic inflammation (AISI), as well as a composite of those markers. The study’s primary
pharmacodynamic assessment focused on changes in this predefined panel of blood-based inflammatory markers of disease. The trial successfully
met this prespecified primary endpoint, with bezisterim demonstrating a statistically significant reduction in the composite neuroinflammation
measure, changing by -0.28 in patients treated with bezisterim compared with +0.19 for placebo (Cohen’s d =-1.06, nominal p=0.0018),
further supporting an effect of bezisterim on neuroinflammatory pathways.
Secondary and exploratory
endpoints evaluated motor and non-motor clinical outcomes, biomarkers of neurodegeneration, and safety and tolerability. The majority
of patients treated with bezisterim showed improvement on the Early Parkinson’s Neuro-Inflammatory Composite 15(EPNIC-15), a composite
endpoint encompassing 15 clinically relevant motor and non-motor measures of PD. In contrast, patients receiving placebo showed a change
in the opposite direction (bezisterim = -0.04, placebo = +0.18, Cohen’s d = -0.94, nominal p=0.0006). EPNIC-15 aligns clinical
outcome measurements from UPDRS Parts I, II, and III, as well as PDSS-2 (sleep) with bezisterim’s proposed mechanism of action
providing a sensitive tool to evaluate anti-inflammatory treatment effects in early PD.
Bezisterim treatment
was also associated with improvements across a range of neurodegeneration biomarkers from mid-study (week 4) to end-of-study (week 12),
including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1(UCHL1), BN02,
and microtubule-associated protein tau (MAPT). These biomarker observations are exploratory in nature, and bezisterim’s potential
to influence underlying disease progression will require confirmation in future clinical trials.
Bezisterim was well
tolerated and demonstrated a safety profile comparable to placebo. The incidence of adverse events was similar between treatment groups
(39.3% with bezisterim vs. 51.7% with placebo), with no severe or serious adverse events and only one treatment-related adverse event
reported in each group. Most adverse events were mild in severity, while patients receiving placebo experienced a higher number of total
adverse events and a greater proportion of moderate adverse events than those treated with bezisterim.
All p-values reported
in these results are nominal and unadjusted for multiplicity, consistent with the exploratory, signal-finding objectives of this Phase
2 study. The FDA has not validated the biomarker endpoints used in this trial as surrogate endpoints for PD. These results are preliminary
and based on a small patient population studied over a limited duration; results observed in this study may not be replicated in larger
or longer-duration trials. We intend to use these results to inform the design of a potentially pivotal Phase 3 registrational trial
of bezisterim in PD.
The previous Phase 2 study of bezisterim
(NE3107) for the treatment of PD (NCT05083260) that we completed in December 2022, was a double-blind, placebo-controlled, safety,
tolerability, and pharmacokinetics study in PD participants treated with carbidopa/levodopa and bezisterim (NE3107). Forty-five
patients with a defined L-dopa “off state” were randomized 1:1 to placebo: bezisterim (NE3107) 20 mg twice daily for 28
days. This trial was launched with two design objectives: 1) the primary objective was safety and a drug-drug interaction study as
requested by the FDA to measure the potential for adverse interactions of bezisterim (NE3107) with carbidopa/ levodopa; and 2) the
secondary objective was to determine if preclinical indications of promotoric activity and apparent enhancement of levodopa activity
could be seen in humans. Both objectives were met.
Long COVID Program
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, generally three months or more.
Common symptoms include lingering loss of smell and taste, extreme fatigue, and “brain fog,” though persistent cardiovascular
and respiratory problems, muscle weakness, and neurologic issues have also been documented.
2
In April 2024, the Company was awarded a clinical
trial grant of $13.1 million from the U.S. Department of War (“DOW”), formerly known as the Department of Defense, awarded
through the Peer Reviewed Medical Research Program of the Congressionally Directed Medical Research Programs. In August 2024, the U.S.
Army Medical Research and Development Command, Office of Human Research Oversight (“OHRO”) approved the Company’s plan
to evaluate bezisterim for the treatment of neurological symptoms that are associated with long COVID and the FDA authorized our Investigational
New Drug (“IND”) application for bezisterim allowing the Company to study a novel, anti-inflammatory approach for the treatment
of the debilitating neurocognitive symptoms associated with long COVID. The Phase 2 ADDRESS-LC study is a randomized (1:1), placebo-controlled,
multicenter trial evaluating the efficacy, safety and tolerability of bezisterim in adult participants with long COVID who have cognitive
impairment sequelae and fatigue. The trial commenced in May 2025 and completed enrollment in May 2026. The Company currently expects to
report topline results in late summer of 2026.
Alzheimer’s Disease
In AD, BioVie has conducted both Phase 2 and Phase
3 trials. Preliminary data from these trials suggest improvements in cognition and biomarkers, supporting further trials to evaluate its
potential as a therapy for the six million Americans living with AD.
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.
On November 29, 2023, the Company announced the
analysis of its unblinded, topline efficacy data from its Phase 3 clinical trial (NCT04669028) of bezisterim in the treatment of mild
to moderate AD. The study had co-primary endpoints measuring cognitive impairment using the Alzheimer’s Disease Assessment Scale-Cognitive
Scale (ADAS-Cog 12) and function using the Clinical Dementia Rating-Sum of Boxes (CDR-SB). Patients were randomly assigned, 1:1 versus
placebo, to receive sequentially 5 mg of bezisterim orally twice a day for 14 days, then 10 mg orally twice a day for 14 days, followed
by 26 weeks of 20 mg orally twice daily.
Upon trial completion, as the Company began the
process of unblinding the trial data, the Company found significant deviation from protocol and current good clinical practices (“cGCPs”)
violations at 15 study sites (virtually all of which were from one geographic area). This highly unusual level of suspected improprieties
led the Company to exclude all patients from these sites and to refer the sites to the FDA Office of Scientific Investigations (“OSI”)
for potential further action. After the patient exclusions, 81 patients remained in the Modified Intent to Treat population, 57 of whom
were in the Per-Protocol population which included those who completed the trial and were verified to take study drug from pharmacokinetic
data.
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 left the trial underpowered for
the primary endpoints. In the Per-Protocol population, which included those patients who completed the trial and who were further verified
to have taken the study drug (based on pharmacokinetic data), an observed descriptive change from baseline appeared to suggest a slowing
of cognitive decline; these same patients experienced an advantage in age deceleration vs. placebo as measured by DNA epigenetic changes.
Age deceleration is used by longevity researchers to measure the difference between the patient’s biological age, in this case as
measured by the Horvath DNA methylation Skin Blood Clock, relative to the patient’s actual chronological age. This test was a non-primary/secondary
endpoint, other-outcome measure, done via blood collected at week 30 (end of study). Additional DNA methylation data continues to be collected
and analyzed.
Liver Cirrhosis Program
In liver disease, our investigational drug candidate
BIV201 (continuous infusion terlipressin) was granted both FDA Fast Track status and FDA Orphan Drug designation for ascites (due to all
etiologies except cancer), which is the most common complication related to liver cirrhosis and represents a significant unmet medical
need. BIV201 is being evaluated as a treatment option for patients suffering from life-threatening complications of liver cirrhosis and
ascites due to hepatitis, nonalcoholic steatohepatitis, and alcoholism. U.S. treatment costs for liver cirrhosis, including ascites and
other complications, are estimated at more than $5 billion annually and have an estimated 50% mortality rate within 6 to 12 months. The
FDA has never approved any drug specifically for treating ascites.
3
After receiving guidance from the FDA regarding
the design of Phase 3 clinical testing of BIV201 for the treatment of patients with cirrhosis and ascites, the Company is currently finalizing
the protocol design for the Phase 3 study of BIV201 with a focus on demonstrating clinical benefit through a composite primary endpoint
of complications and disease progression in patients with cirrhosis and ascites who have recently recovered from acute kidney injury (“AKI”).
Ascites is a common complication of advanced liver cirrhosis involving the accumulation of large volumes of fluid in the abdomen, often
exceeding five liters, due to liver and kidney dysfunction. BIV201 is administered in a continuous infusion of terlipressin as a patent-pending
liquid formulation with patents issued in the U.S., China, Japan, Chile, Australia, Mexico and India to date. Terlipressin is used in
over 40 countries to treat complications of liver cirrhosis, including Type 1 hepatorenal syndrome and bleeding esophageal varices, and
was approved in the U.S. in 2022 to improve kidney function in adults with hepatorenal syndrome experiencing a rapid reduction in kidney
function; it is not currently approved in Japan.
In June 2021, BioVie initiated a Phase 2 study
(NCT04112199) designed to evaluate the efficacy of BIV201 (terlipressin, administered by continuous infusion for two 28-day treatment
cycles) combined with standard-of-care (“SOC”), compared to SOC alone, for the treatment of refractory ascites. The primary
endpoints of the study were the incidence of ascites-related complications and change in ascites fluid accumulation during treatment compared
to a pre-treatment period. By October 12, 2022, there were 15 patients enrolled for treatment and the last patient completed treatment
on May 8, 2023. In March 2023, enrollment was paused and that data from the first 15 patients treated with BIV201 plus SOC appeared to
show at least a 30% reduction in ascites fluid during the 28 days after treatment initiation compared to the 28 days prior to treatment.
The change in ascites volume was significantly different from those patients receiving SOC treatment. Patients who completed the treatment
with BIV201 experienced a 53% reduction in ascites fluid, which was sustained (43% reduction) during the three months after treatment
initiation as compared to the three-month pre-treatment period. In June 2023 and December 2024, BioVie received guidance from the FDA
regarding the design and endpoints for definitive Phase 3 clinical testing of BIV201.
Our proprietary novel
liquid formulation of terlipressin is designed to improve convenience for outpatient administration and avoid potential formulation errors
when pharmacists reconstitute the current powder version of terlipressin. To date, analytical testing results have confirmed room temperature
stability of the prefilled syringe in storage for up to two years. Room temperature storage presents a key product differentiation versus
terlipressin products in countries where the drug is approved. To the best of the Company’s knowledge, all other terlipressin products
sold globally must be stored under refrigeration and there is no prefilled syringe format of terlipressin available for treating patients
in these countries. BioVie has also filed a PCT application covering our novel liquid formulations of terlipressin (international patent
application PCT/US2020/034269, published as WO2020/237170) and to date patents have been granted in the U.S. (Patent No. 12,156,898),
India (Patent No. 540813), Chile (Patent No. 68965), China (Patent No. ZL 202080050758.X), Australia (Patent No. 2020279395), Mexico
(Patent No. 432332) and Japan (Patent No. 7579811).
We believe BIV201 (continuous infusion
terlipressin) has the potential to benefit thousands of patients suffering from life-threatening complications of liver cirrhosis
due to hepatitis, nonalcoholic steatohepatitis, and alcoholism. The FDA has granted Fast-Track status and Orphan Drug designation
for ascites (due to all etiologies except cancer), which is the most common complication related to liver cirrhosis and represents a
significant unmet medical need. Patients with cirrhosis and ascites account for an estimated 116,000 U.S. hospital discharges
annually, with frequent early readmissions. In an analysis of the 2018 HCUP Nationwide Readmissions Database patients hospitalized
with cirrhosis, ascites and paracentesis had an average length of stay of 8.0 days and average hospital charges of $89,136 per
admission. This translates into a total potentially addressable ascites market size for BIV201 therapy exceeding $650 million based
on Company estimates. The FDA has never approved any drug specifically for treating ascites. After receiving guidance from the FDA
in 2023 and again in 2025, the Company is currently finalizing the protocol design for a Phase 3 study of BIV201 with a focus on
demonstrating clinical benefit through a composite primary endpoint of complications and disease progression in patients with
cirrhosis and ascites who have recently recovered from AKI.
The BIV201 development program was initiated by
LAT Pharma LLC. On April 11, 2016, BioVie acquired LAT Pharma LLC and the rights to its BIV201 development program and currently owns
all development and marketing rights to this drug candidate. Pursuant to the Agreement and Plan of Merger entered into on April 11, 2016,
between predecessor entities, LAT Pharma LLC and NanoAntibiotics, Inc., BioVie is obligated to pay a low single digit royalty on net sales
of BIV201 (continuous infusion terlipressin) to be shared among LAT Pharma Members, PharmaIn Corporation, and The Barrett Edge, Inc.
4
Intellectual Property
BIV201
BioVie relies on a
combination of patent, trade secret, other intellectual property laws (such as FDA data exclusivity), nondisclosure agreements, and other
measures to protect our proposed products with layered strategy. We require our employees, consultants, and advisors to execute confidentiality
agreements and to agree to disclose and assign to us all inventions conceived during the workday, using our property, or which relate
to our business. Despite any measures taken to protect our intellectual property (IP), unauthorized parties may attempt to copy aspects
of our products or to obtain and use information that we regard as proprietary.
Neither we nor any
other company has composition of matter patent protection for terlipressin since, as a chemical compound, it is in the public domain
and no longer under a patent. We filed a PCT application covering our novel liquid formulations of terlipressin (international patent
application PCT/US2020/034269, published as WO2020/237170) and are seeking patent protection in the U.S., Europe, China, Japan and other
jurisdictions. To date patents have been granted in the U.S. (Patent No. 12,156,898), India (Patent No. 540813), Chile (Patent No. 68965),
China (Patent No. ZL 202080050758.X), Japan (Patent No. 7579811), Australia (Patent No. 2020279395) and Mexico (Patent No. 432332). Also,
we own U.S. Patent Nos. 11,364,277 and 12,685,756, and European Patent No. EP3347032, which are directed to various methods of treating
ascites with BIV201, and we are pursuing additional patent coverage in the U.S., Japan, Europe, China and others. The patents and pending
patent applications and their projected expiration dates are provided below.
5
BIV201 was awarded Orphan Drug Designations in
the U.S. for the treatment of hepatorenal syndrome on November 21, 2018 and treatment of ascites due to all etiologies except cancer on
September 8, 2016. If a drug receives Orphan Drug Designation and subsequently gains FDA approval for the designated rare disease, it
earns seven years of market exclusivity in the U.S. (10 years in the EU). During this period, the FDA cannot approve another application
for the same drug for the same indication, except under limited circumstances. This exclusivity is independent of patents, meaning even
if a patent expires, orphan exclusivity can still block competitors.
Bezisterim (NE3107) and related compounds
As of July 31, 2026, we have twelve (12) issued
U.S. patents, seven (7) pending U.S. patent applications, three (3) pending U.S. PCT applications, four (4) issued foreign patents, and
nine (9) pending foreign patent applications directed to protecting NE3107 and related compounds and methods of making and using thereof.
The U.S. patents and pending patent applications and their projected expiration dates are provided below.
Title Patent Application Number Patent Number Projected Expiration Date
Compositions for Treatment of Neurodegenerative Conditions 18/511,027 pending -
Methods of Treating Long COVID 19/742590 pending -
Methods for the Treatment of Biological Aging 19/190210 pending
Methods for the Treatment of Mild Cognitive Impairment 19/055380 pending -
Assay and Methods for Drug Discovery 19/265505 pending -
Government Regulation
Government authorities in the United States, at
the federal, state and local level, and in other countries extensively regulate, among other things, the research, development, testing,
manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval
monitoring and reporting, marketing and export and import of products such as those we are developing. Any pharmaceutical candidate that
we develop must be approved by the FDA before it may be legally marketed in the United States and by the appropriate foreign regulatory
agency before it may be legally marketed in foreign countries.
United States Drug Development Process
In the United States, the FDA regulates the development
of drugs and biologic products under the FDCA and the Public Health Services Act ("PHSA"), respectively. Drugs, biologics and
medical devices are also subject to other federal, state and local statutes and regulations.
6
Biologics are subject to regulation by the FDA
under the FDCA, the PHSA and related regulations, and other federal, state and local statutes and regulations. The process of obtaining
regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require
the expenditure of substantial time and financial resources. Failure to comply with the applicable United States requirements at any time
during the product development process, approval process or after approval, may subject an applicant to administrative or judicial sanctions.
FDA sanctions could include refusal to approve pending applications, withdrawal of an approval, a clinical hold, warning letters, product
recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts,
restitution, disgorgement or civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect
on us.
The process required by the FDA before a drug
or biological product may be marketed in the United States generally involves the following:
· FDA review and approval of the NDA or BLA.
The lengthy process of seeking required approvals
and the continuing need for compliance with applicable statutes and regulations require the expenditure of substantial resources. There
can be no certainty that approvals will be granted.
Clinical trials involve the administration of
the drug or biological candidate to healthy volunteers or patients having the disease being studied under the supervision of qualified
investigators, generally physicians not employed by or under the trial sponsor’s control. Clinical trials are conducted under protocols
detailing, among other things, the objectives of the clinical trial, dosing procedures, subject inclusion and exclusion criteria, and
the parameters to be used to monitor subject safety. Each protocol must be submitted to the FDA as part of the IND. Clinical trials must
be conducted in accordance with the FDA’s cGCP requirements. Further, each clinical trial must be reviewed and approved by an IRB,
at or servicing each institution at which the clinical trial will be conducted. An IRB is charged with protecting the welfare and rights
of trial participants and considers such items as whether the risks to individuals participating in the clinical trials are minimized
and are reasonable in relation to anticipated benefits. The IRB also approves the informed consent form that must be provided to each
clinical trial subject or his or her legal representative and must monitor the clinical trial until it is completed.
Human clinical trials prior to approval are typically
conducted in three sequential phases that may overlap or be combined:
7
Post-approval studies, or Phase 4 clinical trials,
may be conducted after initial marketing approval. These studies are used to gain additional experience from the treatment of patients
in the intended therapeutic indication and may be required by the FDA as part of the approval process.
Progress reports detailing the results of the
clinical trials must be submitted at least annually to the FDA and written IND safety reports must be submitted to the FDA by the investigators
for serious and unexpected adverse events or any finding from tests in laboratory animals that suggests a significant risk for human subjects.
Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, if at all. The FDA or the
sponsor or its data safety monitoring board may suspend a clinical trial at any time on various grounds, including a finding that the
research subjects or patients are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of
a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if
the drug or biologic has been associated with unexpected serious harm to patients.
Concurrent with clinical trials, companies usually
complete additional animal studies and develop additional information about the chemistry and physical characteristics of the drug or
biologic as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The
manufacturing process must be capable of consistently producing quality batches of the drug or biological candidate and, among other things,
must include methods for testing the identity, strength, quality and purity of the final drug or biologic. Additionally, appropriate packaging
must be selected and tested and stability studies must be conducted to demonstrate that the drug or biological candidate does not undergo
unacceptable deterioration over its shelf life.
U.S. Review and Approval Processes
The results of product development, preclinical
studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry of the
drug or biologic, proposed labeling and other relevant information are submitted to the FDA as part of an NDA or BLA requesting approval
to market the product. The submission of an NDA or BLA is subject to the payment of substantial user fees; a waiver of such fees may be
obtained under certain limited circumstances.
The FDA reviews all NDAs and BLAs submitted before
it accepts them for filing and may request additional information rather than accepting an NDA or BLA for filing. Once the submission
is accepted for filing, the FDA begins an in-depth review of the NDA or BLA.
After the NDA or BLA submission is accepted for
filing, the FDA reviews the NDA to determine, among other things, whether the proposed product is safe and effective for its intended
use, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, strength,
quality and purity. The FDA reviews a BLA to determine, among other things, whether the product is safe, pure and potent and the facility
in which it is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, purity
and potency. In addition to its own review, the FDA may refer applications for novel drug or biological products or drug or biological
products which present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians
and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.
During the approval process, the FDA also will determine whether a risk evaluation and mitigation strategy, or REMS, is necessary to assure
the safe use of the drug or biologic. If the FDA concludes that a REMS is needed, the sponsor of the NDA or BLA must submit a proposed
REMS; the FDA will not approve the NDA or BLA without a REMS, if required.
Before approving an NDA or BLA, the FDA will inspect
the facilities at which the product is to be manufactured. The FDA will not approve the product unless it determines that the manufacturing
processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required
specifications. Additionally, before approving an NDA or BLA, the FDA will typically inspect one or more clinical sites to assure compliance
with cGMP. If the FDA determines the application, manufacturing process or manufacturing facilities are not acceptable it will outline
the deficiencies in the submission and often will request additional testing or information.
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The NDA or BLA review and approval process is
lengthy and difficult and the FDA may refuse to approve an NDA or BLA if the applicable regulatory criteria are not satisfied or may require
additional clinical data or other information. Even if such data and information is submitted, the FDA may ultimately decide that the
NDA or BLA does not satisfy the criteria for approval. Data obtained from clinical trials are not always conclusive and may be susceptible
to varying interpretations, which could delay, limit or prevent regulatory approval. The FDA will issue a “complete response”
letter if the agency decides not to approve the NDA or BLA. The complete response letter describes all of the specific deficiencies in
the NDA or BLA identified by the FDA. The deficiencies identified may be minor, for example, requiring labeling changes, or major, for
example, requiring additional clinical trials. Additionally, the complete response letter may include recommended actions that the applicant
might take to place the application in a condition for approval. If a complete response letter is issued, the applicant may either resubmit
the NDA or BLA, addressing all of the deficiencies identified in the letter, or withdraw the application.
If a product receives regulatory approval, the
approval may be limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the
commercial value of the product. Further, the FDA may require that certain contraindications, warnings or precautions be included in the
product labeling. In addition, the FDA may require Phase 4 testing which involves clinical trials designed to further assess a product’s
safety and effectiveness and may require testing and surveillance programs to monitor the safety of approved products that have been commercialized.
Orphan Drug Designation
Under the Orphan Drug Act, the FDA may grant orphan
designation to a drug or biological product intended to treat a rare disease or condition, which is generally a disease or condition that
affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States and for which there
is no reasonable expectation that the cost of developing and making a drug or biological product available in the United States for this
type of disease or condition will be recovered from sales of the product. Orphan product designation must be requested before submitting
an NDA or BLA. After the FDA grants orphan product designation, the identity of the therapeutic agent and its potential orphan use are
disclosed publicly by the FDA. Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review
and approval process.
If a product that has Orphan designation subsequently
receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product
exclusivity, which means that the FDA may not approve any other applications to market the same drug or biological product for the same
indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity.
Competitors, however, may receive approval of different products for the indication for which the Orphan product has exclusivity or obtain
approval for the same product but for a different indication for which the Orphan product has exclusivity. Orphan product exclusivity
also could block the approval of one of our products for seven years if a competitor obtains approval of the same drug or biological product
as defined by the FDA or if our drug or biological candidate is determined to be contained within the competitor’s product for the
same indication or disease. If a drug or biological product designated as an orphan product receives marketing approval for an indication
broader than what is designated, it may not be entitled to orphan product exclusivity. Orphan Drug status in the EU has similar but not
identical benefits in the EU.
Expedited Development and Review Programs
The FDA has a Fast Track program that is intended
to expedite or facilitate the process for reviewing new drug and biological products that meet certain criteria. Specifically, new drug
and biological products are eligible for Fast Track designation if they are intended to treat a serious or life-threatening condition
and demonstrate the potential to address unmet medical needs for the condition. Fast Track designation applies to the combination of the
product and the specific indication for which it is being studied. Unique to a Fast Track product, the FDA may consider for review sections
of the NDA or BLA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission
of the sections of the NDA or BLA, the FDA agrees to accept sections of the NDA or BLA and determines that the schedule is acceptable,
and the sponsor pays any required user fees upon submission of the first section of the NDA or BLA.
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Any product submitted to the FDA for marketing
approval, including those submitted to a Fast Track program, may also be eligible for other types of FDA programs intended to expedite
development and review, such as priority review and accelerated approval. Any product is eligible for priority review if it has the potential
to provide safe and effective therapy where no satisfactory alternative therapy exists or a significant improvement in the treatment,
diagnosis or prevention of a disease compared with marketed products. The FDA will attempt to direct additional resources to the evaluation
of an application for a new drug or biological product designated for priority review in an effort to facilitate the review. Additionally,
a product may be eligible for accelerated approval. Drug or biological products studied for their safety and effectiveness in treating
serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated
approval, which means that they may be approved on the basis of adequate and well-controlled clinical studies establishing that the product
has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit, or on the basis of an effect on a clinical
endpoint other than survival or irreversible morbidity. As a condition of approval, the FDA generally requires that a sponsor of a drug
or biological product receiving accelerated approval perform adequate and well-controlled post-marketing clinical studies to establish
safety and efficacy for the approved indication. Failure to conduct such studies or conducting such studies that do not establish the
required safety and efficacy may result in revocation of the original approval. In addition, the FDA currently requires as a condition
for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch or subsequent
marketing of the product. Fast Track designation, priority review and accelerated approval do not change the standards for approval but
may expedite the development or approval process.
Post-Approval Requirements
Any drug or biological products for which we receive
FDA approvals are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, reporting of
adverse experiences with the product, providing the FDA with updated safety and efficacy information on an annual basis or as required
more frequently for specific events, product sampling and distribution requirements, complying with certain electronic records and signature
requirements and complying with FDA promotion and advertising requirements, which include, among others, standards for direct-to-consumer
advertising, prohibitions against promoting drugs and biologics for uses or in patient populations that are not described in the drug’s
or biologic’s approved labeling (known as “off-label use”), rules for conducting industry-sponsored scientific and educational
activities, and promotional activities involving the internet. Failure to comply with FDA requirements can have negative consequences,
including the immediate discontinuation of noncomplying materials, adverse publicity, enforcement letters from the FDA, mandated corrective
advertising or communications with doctors, and civil or criminal penalties. Although physicians may prescribe legally available drugs
and biologics for off-label uses, manufacturers may not market or promote such off-label uses.
We will need to rely on third parties for the
production of our product candidates. Manufacturers of our product candidates are required to comply with applicable FDA manufacturing
requirements contained in the FDA’s cGMP regulations. cGMP regulations require among other things, quality control and quality assurance
as well as the corresponding maintenance of comprehensive records and documentation. Drug and biologic manufacturers and other entities
involved in the manufacture and distribution of approved drugs and biologics are also required to register their establishments and list
any products made there with the FDA and comply with related requirements in certain states, and are subject to periodic unannounced inspections
by the FDA and certain state agencies for compliance with cGMP and other laws. Accordingly, manufacturers must continue to expend time,
money and effort in the area of production and quality control to maintain cGMP compliance. Discovery of problems with a product after
approval may result in serious and extensive restrictions on a product, manufacturer, or holder of an approved NDA or BLA, including suspension
of a product until the FDA is assured that quality standards can be met, continuing oversight of manufacturing by the FDA under a “consent
decree,” which frequently includes the imposition of costs and continuing inspections over a period of many years, and possible
withdrawal of the product from the market. In addition, changes to the manufacturing process generally require prior FDA approval before
being implemented and other types of changes to the approved product, such as adding new indications and additional labeling claims, are
also subject to further FDA review and approval.
The FDA also may require post-marketing testing,
known as Phase 4 testing, risk minimization action plans and surveillance to monitor the effects of an approved product or place conditions
on an approval that could otherwise restrict the distribution or use of the product.
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Employees
Our business is managed by our officers who consist
of Mr. Cuong Do, Chief Executive Officer & President; Dr. Joseph M Palumbo, Executive Vice President - Chief Medical Officer; and
Wendy Kim, Chief Financial Officer and Corporate Secretary. These individuals devote their full-time efforts to Company activities. The
Company has 13 employees which are all full time. We also rely on a team of highly experienced scientific, medical, and regulatory consultants
to conduct product development activities.
Available Information
We maintain a website at www.bioviepharma.com.
Information on our website is not incorporated by reference into this report and does not constitute a part of this report. We make
available, free of charge, on our website our annual report on Form 10-K, quarterly reports on Form 10-Q, current reports on Form
8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934,
as amended, as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. These reports
are also available at the SEC’s website at www.sec.gov.
ITEM 1A. RISK FACTORS
Our business, financial condition, operating results
and prospects are subject to the following risks. Additional risks and uncertainties not presently foreseeable to us may also impair our
business operations. If any of the following risks or the risks described elsewhere in this report actually occur, our business, financial
condition or operating results could be materially adversely affected. In such case, the trading price of our Class A Common Stock, par
value $0.0001 (“Common Stock”) could decline, and our stockholders may lose all or part of their investment.
Risk Factor Summary
Our business operations are subject to numerous
risks, factors and uncertainties, including those outside of our control, which could cause our actual results to be harmed, including
risks regarding the following:
Risks Relating to Our Business and Industry
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· We may not be able to attract and retain highly skilled personnel.
Risks Relating to Our Intellectual Property
· Intellectual property rights do not necessarily address all potential threats.
Risks Relating to Our Common Stock
· The market price and trading volume of our Common Stock may be volatile.
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Risks Relating to Our Business and Industry
We rely and will continue to rely on third
parties to conduct our clinical trials. If these third parties do not successfully carry out their contractual duties or meet expected
deadlines or do not successfully perform and comply with regulatory requirements, we may not be able to obtain regulatory approval of
or commercialize our product candidates.
We depend, and will continue
to depend, on third parties, including, but not limited to, contract research organizations (“CROs”), clinical trial sites
and clinical trial principal investigators, contract laboratories, independent institutional review boards (“IRBs”), manufacturers,
suppliers, and other third parties to conduct our clinical trials, including those for our drug candidates bezisterim (NE3107) and BIV201.
We rely heavily on these third parties over the course of our clinical trials, and we control only certain aspects of their activities.
Nevertheless, we retain ultimate responsibility for ensuring that each of our studies is conducted in accordance with the protocol and
applicable legal, regulatory, and scientific standards and regulations, and our reliance on third parties does not relieve us of our regulatory
responsibilities. We and these third parties are required to comply with cGCPs, which are regulations and guidelines enforced by the FDA
and comparable foreign regulatory authorities for the conduct of clinical trials on product candidates in clinical development. Regulatory
authorities enforce cGCPs through periodic inspections and for-cause inspections of clinical trial principal investigators and trial sites.
If, due to the failure of either us or a third party, a clinical trial fails to comply with applicable cGCPs, FDA’s IND requirements,
other applicable regulatory requirements, or requirements set forth in the applicable IRB-approved protocol, we may be required to conduct
additional clinical trials to support our marketing applications, which would delay the regulatory approval process. For example, our
drug product candidate bezisterim (NE3107) was cleared by FDA for use in a Phase 3, randomized, double blind, placebo controlled, parallel
group, multicenter study in subjects who have mild to moderate AD. Enrollment in that trial began in August 2021, with a planned primary
completion in late 2022/early 2023. On November 29, 2023, we announced topline efficacy data from its Phase 3 clinical trial (NCT04669028)
of bezisterim (NE3107) in the treatment of mild to moderate AD. Upon trial completion, as we began the process of analyzing the trial
data, we found significant deviations from the protocol and cGCP violations at 15 study sites (virtually all of which were from one geographic
area). This highly unusual level of suspected improprieties led us to exclude all patients from these sites. We subsequently notified
FDA’s OSI of such significant deviations from study protocol, the suspected improprieties, and the study sites involved. The identification
of significant deviations from study protocol and numerous GCP violations at multiple study sites raised questions regarding the validity
and robustness of data from these study sites. The unplanned exclusion of so many patients left the trial underpowered for its primary
endpoints. However, based on the remaining dataset from those other sites determined to be in compliance with the protocol and GCP’s,
a preliminary signal of efficacy was detected.
Although we design the
clinical trials for our product candidates, our CROs are tasked with facilitating and monitoring these trials. As a result, many aspects
of our clinical development programs, including site and investigator selection, and the conduct, timing, and monitoring of the study,
is outside our direct control, either partially or in whole. Our reliance on third parties to conduct clinical trials also results in
less direct control over the collection, management, and quality of data developed through clinical trials than would be the case if we
were relying entirely upon our own employees. Communicating with third parties can also be challenging, potentially leading to mistakes
as well as difficulties in coordinating activities. Our business may be impacted if any of these third parties violates applicable federal,
state, or foreign laws and/or regulations, including but not limited to FDA’s IND regulations, cGCPs, fraud and abuse or false claims
laws, healthcare privacy and data security laws, or provide us or government agencies with inaccurate, misleading, or incomplete data.
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Successful development of biopharmaceuticals
is highly uncertain and is dependent on numerous factors, many of which are beyond our control.
Product candidates that appear promising in the
early phases of development may fail to reach the market for several reasons. Pre-clinical study results may show the product candidate
to be less effective than desired (e.g., the study failed to meet its primary endpoints) or to have harmful or problematic side effects.
Product candidates may fail to receive the necessary regulatory approvals or may be delayed in receiving such approvals. Among other things,
such delays may be caused by slow enrollment in clinical studies; length of time to achieve study endpoints; additional time requirements
for data analysis; IND and later new drug application preparation; discussions with the FDA; an FDA request for additional pre-clinical
or clinical data; unexpected safety or manufacturing issues; manufacturing costs; pricing or reimbursement issues; clinical sites deviating
from the trial protocol, committing scientific misconduct, or other violations of regulatory requirements - which can render data from
those sites unusable in support of regulatory approval; or other factors that make the product not economical. Proprietary rights of others
and their competing products and technologies may also prevent the product from being commercialized.
Success in pre-clinical and early clinical studies
does not ensure that large-scale clinical studies will be successful. Clinical results are frequently susceptible to varying interpretations
that may delay, limit or prevent regulatory approvals. The length of time necessary to complete clinical studies and to submit an application