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Item 1. Business

2022-09-27 compared with 2021-08-30 · 344 added, 350 removed, 256 unchanged (73% of the section changed)

is a clinical-stage company developing innovative drug

therapies to overcome unmet medical needs in chronic debilitating conditions.

is a clinical-stage company developing innovative drug therapies

to overcome unmet medical needs in chronic debilitating conditions.

In liver disease , our Orphan Drug candidate BIV201 (continuous

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The initial target for BIV201 therapy is refractory

These patients suffer from frequent life-threatening complications, generate more than $5 billion in annual treatment costs,

and have an estimated 50% mortality rate within 6 to 12 months.

The FDA has never approved any drugs to treat refractory ascites.

2a clinical trial of BIV201 was completed in 2019, and a multi-center, randomized and controlled Phase 2b trial is currently underway

at several US medical centers including Vanderbilt University, the Mayo Clinic, and University of Pennsylvania (NCT NCT04112199).

results are expected in early 2022, to be followed by a proposed single pivotal Phase 3 trial beginning in 2022.

In June 2021, BioVie

received written feedback from the FDA in response to a Type B meeting request to conduct a pivotal US Phase 3 clinical trial in HRS-AKI,

which is a life-threatening complication of advanced ascites.

Based on the guidance received, we are revising certain elements of our

proposed study and are planning to initiate this study in late 2021.

In neurodegenerative disease, BioVie acquired the biopharmaceutical assets of NeurMedix, Inc., a privately held

clinical-stage pharmaceutical company, in June 2021.

The acquired assets include NE3107, a potentially selective inhibitor of inflammatory

ERK signaling which, based on animal studies is believed to reduce neuroinflammation.

NE3107 is a novel orally administered small molecule

that is thought to inhibit inflammation-driven insulin resistance and major pathological inflammatory cascades with a novel mechanism

There is emerging scientific consensus that both inflammation and insulin resistance play fundamental roles in the development

of Alzheimers and Parkinsons Disease, and NE3107 could, if approved, represent an entirely new medical approach to treating

these devastating conditions affecting an estimated 6 million Americans suffering from Alzheimers and 1 million from Parkinsons.

The FDA has authorized a potentially pivotal Phase 3 randomized, double-blind, placebo-controlled, parallel group, multicenter study

to evaluate NE3107 in subjects who have mild to moderate Alzheimers disease (NCT04669028).

BioVie is planning to initiate this

trial in the second half of 2021 and is targeting primary completion in late 2022.

In addition to Alzheimers disease, the Company

plans to advance NE3107 in Parkinsons based on promising results from preclinical studies.

Inflammation-driven insulin resistance

is implicated in a broad range of serious diseases, including multiple myeloma and prostate cancer, and we plan to begin exploring these

opportunities in the coming months using NE3107 or related compounds acquired in the NeurMedix asset purchase.

Pipeline Overview

The following diagram shows our clinical development pipeline as of

These patients suffer from frequent life-threatening complications, generate

more than $5 billion in annual treatment costs, and have an estimated 50% mortality rate within 6 to 12 months.

The US Food and Drug Administration

(FDA) has not approved any drug to treat refractory ascites.

A Phase 2a clinical trial of BIV201 was completed in 2019, and a multi-center,

randomized 30-patient Phase 2b trial is currently underway.

As of June 30, 2022, eleven US study centers had been activated and are actively

screening and enrolling patients in the study.

Top-line results from this trial are expected in mid calendar year 2023.

The BIV201 development program was initiated by LAT Pharma LLC.

11, 2016, the Company acquired LAT Pharma LLC and the rights to its BIV201 development program.

The Company currently owns all development

and marketing rights to its drug candidate.

Pursuant to the Agreement and Plan of Merger entered into on April 11, 2016, between our 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.

In neurodegenerative disease, BioVie acquired the biopharmaceutical

assets of NeurMedix, Inc., a related party privately held clinical-stage pharmaceutical company and related party affiliate, in June 2021.

The acquired assets include NE3107, a potentially selective inhibitor of inflammatory ERK signaling that, based on animal studies, is

believed to reduce neuroinflammation.

NE3107is a 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 and Parkinson’s

Disease, and NE3107 could, if approved, represent an entirely new medical approach to treating these devastating conditions affecting

an estimated 6 million Americans suffering from Alzheimer’s and 1 million from Parkinson’s.

The FDA has authorized a potentially

pivotal Phase 3 randomized, double-blind, placebo-controlled, parallel group, multicenter study to evaluate NE3107 in subjects who have

mild to moderate Alzheimer’s disease (NCT04669028).

We initiated this trial on August 5, 2021 and are targeting primary completion

in mid calendar year 2023.

On January 20, 2022, the Company initiated a study by treating the first patient, in its Phase 2 study assessing

NE3107’s safety and tolerability and potential pro-motoric impact in Parkinson’s disease patients.

The NM201 study (NCT05083260)

is a double-blind, placebo-controlled, safety, tolerability, and pharmacokinetics study in Parkinson’s Disease (PD).

will be treated with carbidopa/levodopa and NE3107 or placebo.

Forty patients with a defined PD medication “off state” will

be randomized 1:1 placebo to active NE3107 20 mg twice daily for 28 days.

Safety assessments will look at standard measures of patient

health and potential for drug-drug interactions affecting L-dopa pharmacokinetics and activity.

Exploratory efficacy assessments will

use the Motor Disease Society Unified Parkinson’s Disease Rating (MDS-UPDRS) parts 1-3, ON/OFF Diary, and Non-Motor Symptom Scale.

Topline results are expected for the NM201 study by the end of the calendar year 2022.

Investigator-Initiated Trial in MCI and Mild Alzheimer’s Disease,

The Company provided the financial support and the use of our NE3107

formulated drug product to The Regenesis Project of Dr Sheldon Jordan in an open-label phase 2 study in Dr.

Sheldon’s patients

with Alzheimer’s disease related dementias.

The study received FDA authorization on December 12, 2021and was designed to measure

NE3107’s effect on cognition, cerebral spinal fluid (“CSF”) and blood biomarkers, and neuro-imagining endpoints.

study seeks to measure changes in cognition through verbal and visual test procedures and changes in biomarkers of Alzheimer's disease

and inflammatory and metabolic parameters that can be measured in the central nervous system with advanced neuroimaging techniques in

patients before and after treatment with 20 mg of NE3107 twice daily for 3 months following three months of treatment.

Data analysis for the study is expected to be in completed in second half

of the calendar year 2022.

Inflammation-driven insulin resistance is believed to be implicated

in a broad range of serious diseases, including multiple myeloma and prostate cancer, and we plan to begin exploring these opportunities

in the coming months using NE3107 or related compounds acquired in the NeurMedix asset purchase.

NE3107 is patented in the United States,

Australia, Canada, Europe and South Korea.

Liver Cirrhosis Program

BioVies orphan drug candidate BIV201 (continuous infusion

terlipressin) represents a novel investigational approach to the treatment of ascites due to chronic liver cirrhosis.

based on a drug that is approved in about 40 countries to treat related complications of liver cirrhosis (part of the same disease

pathway as ascites), but not yet available in the United States.

The active agent in BIV201, terlipressin, is a potent

vasoconstrictor and is marketed in multiple foreign countries.

The goal of the BIV201 development program is focused on interrupting

the ascites disease pathway, thereby halting the cycle of accelerating fluid generation in ascites patients.

completed a Phase 2a clinical trial of BIV201 in six patients with refractory as cites due to advanced liver cirrhosis at the

McGuire Research Institute in Richmond, VA.

In April 2019, we announced top-line results for this clinical trial.

The following

results were observed:

● Continuous infusion of terlipressin via portable infusion pump

was maintained for 28 days in three patients with refractory ascites, and all patients remained hemodynamically stable during treatment.

● The steady state plasma concentration data characterized terlipressin

pharmacokinetics (PK) within the predicted PK model concentrations.

● Four of the six patients treated with BIV201 experienced an

increase in the number of days between paracenteses ranging from 71% to 414% compared to prior to initiating therapy.

In June 2019, we met with representatives of the FDA for a Type C

Guidance Meeting to plan our next clinical study in ascites.

We discussed our clinical development program with the FDA and proposed

safety and efficacy endpoints required for future marketing approval.

In September 2019, the FDA granted our Type B meeting request and

committed to providing feedback in early 2020 for our proposed clinical trial design.

BioVie’s orphan drug candidate BIV201 (continuous infusion terlipressin)

represents a novel approach to the treatment of ascites due to chronic liver cirrhosis.

BIV201 is based on a drug that is approved in

about 40 countries to treat related complications of liver cirrhosis (part of the same disease pathway as ascites), but not yet available

in the United States.

The active agent in BIV201, terlipressin, is a potent vasoconstrictor and is marketed in multiple foreign countries.

The goal of BIV201 therapy is to interrupt the ascites disease pathway, thereby halting the cycle of accelerated fluid generation in ascites

In 2017, we began administering BIV201 to patients at the McGuire Research

Institute Inc.

in Richmond, VA.

In April 2019, we announced top-line results for our Phase 2a clinical trial of BIV201 (continuous infusion

terlipressin) in six patients with refractory ascites due to advanced liver cirrhosis.

The following results were observed:

Continuous infusion of terlipressin via portable infusion pump was maintained for 28 days in three patients with refractory ascites, and all patients remained hemodynamically stable during treatment.

The steady state plasma concentration data characterized terlipressin pharmacokinetics (PK) within the predicted PK model concentrations.

Four of the six patients treated with BIV201 experienced an increase in the number of days between paracenteses ranging from 71% to 414% compared to prior to initiating therapy.

In June 2019, we met with representatives of the FDA for a Type C Guidance

Meeting to plan our next clinical study in ascites.

We discussed our clinical development program with the FDA and proposed safety and

efficacy endpoints required for future marketing approval.

In September 2019, the FDA granted our Type B meeting request and committed

to providing feedback in early 2020 for our proposed clinical trial design.

In April 2020, we received the FDA’s written response

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Subsequently we received further guidance from the

Based on this guidance, the Company finalized the clinical trial protocol and began preparing for a randomized 30-patient Phase

Based on this guidance, the Company finalized the clinical trial protocol and prepared for a randomized 30-patient Phase 2b study.

The IND for this study was submitted and has become effective.

As of July 2021, seven of nine planned US study centers have

been activated and are actively screening patients, and two patients have been enrolled in the study.

We plan to follow this study with

a larger potentially pivotal Phase 3 clinical trial expected to begin in 2022.

The FDA communicated that pending positive Phase 2 study

results, a sufficiently large and well-controlled Phase 3 trial, with supportive trend data from the Phase 2b (statistical significance

not required), could potentially yield the clinical data needed to apply for BIV201 marketing approval.

The Phase 2b clinical trial protocol

is summarized on www.clinicaltrials.gov, trial identifier NCT04112199.

We have invented a proprietary novel liquid formulation of terlipressin that is intended to improve convenience

for outpatient administration and avoid potential formulation errors when pharmacists reconstitute the powder version.

In November 2019,

we announced the completion of quality control testing and released the batch for use in our next clinical trial pending FDA clearance.

In March 2020, we submitted a detailed information package to the FDAs CMC division.

In May 2020, we received CMC division clearance

to use the new BIV201 prefilled terlipressin syringe in the current Phase 2b trial subject to conducting certain additional standard

analytical testing which has been successfully completed.

As of June 2021, analytical testing results have confirmed room temperature

stability of the prefilled syringe in storage for 18 months, with the potential for up to two years of stability (yet to be confirmed).

Room temperature storage presents a key product differentiation versus terlipressin products in countries where the drug is approved.

To the best of the Companys 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 Patent Cooperation

Treaty (PCT) application covering our novel liquid formulations of terlipressin (international patent application PCT/US2020/034269,

published as WO2020/237170) and we plan to seek patent protection in at least the United States, Europe, China and Japan.

The Phase 2b study was initiated in June 2021.

As of July 2022, eleven

planned US study centers have been activated.

We plan to follow this study with a larger potentially pivotal Phase 3 clinical trial expected

to begin in 2023.

The FDA communicated that pending positive Phase 2 study results, a sufficiently large and well-controlled Phase 3 trial,

with supportive trend data from the Phase 2b (statistical significance not required), could potentially yield the clinical data needed

to apply for BIV201 marketing approval.

The Phase 2b clinical trial protocol is summarized on www.clinicaltrials.gov, trial identifier

We have invented a proprietary novel liquid formulation of terlipressin

which is currently being studied in the above clinical studies intended to improve convenience for outpatient administration and avoid

potential formulation errors when pharmacists reconstitute the powder version.

In May 2020, we received CMC division clearance to use

the new BIV201 prefilled terlipressin syringe in the current Phase 2b trial subject to conducting certain additional standard analytical

testing which has been successfully completed.

To date analytical testing results have confirmed room temperature stability of the prefilled

syringe in storage for 18 months, with the potential for up two years stability.

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 Patent Cooperation Treaty (“PCT”) application covering our novel liquid

formulations of terlipressin (international patent application PCT/US2020/034269, published as WO2020/237170) and we plan to seek patent

protection in at least the United States, Europe, China and Japan.

BIV201 (continuous infusion terlipressin) has the potential to improve

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The BIV201 development program began at LAT Pharma LLC.

2016, we acquired LAT Pharma LLC and the rights to its BIV201 development program and currently own all development and marketing rights

to the product candidate.

On April 11, 2016,

we acquired LAT Pharma LLC and the rights to its BIV201 development program and currently own all development and marketing rights to

the product candidate.

We and PharmaIN, LAT Pharma’s former partner focused on the development of new modified product candidates

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PharmaIN’s rights to our program remain unchanged.

We have a pending U.S.

patent application 16/379,446 (a continuation application related to the 945 Patent) for the use of BIV201

for the treatment of patients diagnosed with ascites due to liver cirrhosis in the outpatient setting using ambulatory pump infusion,

and have corresponding patent applications pending in Japan, Europe, China and Hong Kong.

Our pending U.S patent (a continuation application related to the ’945 Patent) for the use of BIV201 as a monotherapy for the treatment

of patients diagnosed with ascites due to liver cirrhosis in the outpatient setting using ambulatory pump infusion, issued on June 21,

2022 (U.S 11,364,277).

Corresponding patent applications are pending in Japan, Europe, China and Hong Kong.

About Ascites and Liver Cirrhosis

About 600,000 Americans and millions worldwide suffer from liver

Cirrhosis is the 11th leading cause of death due to disease in the US, killing more than 40,000 people each year.

The condition

results primarily from hepatitis, alcoholism, and fatty liver disease linked to obesity.

Ascites is a common complication of advanced

liver cirrhosis, involving kidney dysfunction and the accumulation of large amounts of fluid in the abdominal cavity.

Cirrhosis is a leading cause of death in the US.

The condition results

primarily from hepatitis, alcoholism, and fatty liver disease linked to obesity.

Ascites is a common complication of advanced liver cirrhosis,

involving kidney dysfunction and the accumulation of large amounts of fluid in the abdominal cavity.

The Need for an Ascites Therapy

With no medications approved by the FDA specifically for treating

ascites, an estimated 40% of patients die within two years of diagnosis.

Certain drugs approved for other uses such as diuretics may

provide initial relief, but patients may fail to respond to treatment as ascites worsens.

With no medications approved by the FDA specifically for treating ascites,

an estimated 40% of patients die within two years of diagnosis.

Certain drugs approved for other uses such as diuretics may provide initial

relief, but patients may fail to respond to treatment as ascites worsens.

This represents a critical unmet medical need.

treatment costs for liver cirrhosis, including ascites and other complications, are estimated at more than $5 billion annually.

costs for liver cirrhosis, including ascites and other complications, are estimated at more than $5 billion annually.

The Ascites Development Pathway

Most experts agree that ascites develops through a sequence of events

illustrated by the above diagram.

High blood pressure in the vein that supplies blood to the liver, called portal hypertension,

occurs as increasing liver damage (fibrosis) impedes blood flow through the liver.

This causes vasodilation and blood pooling in

the central or splanchnic region of the body and low blood volume in the arteries.

The decrease in effective blood volume

activates a signaling pathway (neurohormonal systems) which tells the kidneys to retain large amounts of salt and water

in an effort to increase blood volume.

Ultimately the retention of excess sodium and water leads to the formation of ascites as these

substances weep from the liver and lymph system and collect in the patients abdomen.

Most experts agree that ascites develops through a sequence of events illustrated

by the above diagram.

High blood pressure in the vein that supplies blood to the liver, called “portal hypertension,” occurs

as increasing liver damage (fibrosis) impedes blood flow through the liver.

This causes vasodilation and blood pooling in the central

or “splanchnic” region of the body and low blood volume in the arteries.

The decrease in effective blood volume activates

a signaling pathway (“neurohormonal systems”) which tells the kidneys to retain large amounts of salt and water in an effort

to increase blood volume.

Ultimately the retention of excess sodium and water leads to the formation of ascites as these substances “weep”

from the liver and lymph system and collect in the patient’s abdomen.

The BIV201 Mechanism of Action

BIV201 is being developed with the goal of alleviating the portal

hypertension and correcting splanchnic vasodilation, thereby increasing effective blood volume and reducing the signals to

the kidneys to retain excess salt and water.

If successful, BIV201 could halt the cycle of accelerating fluid generation in ascites patients

and reduce the need for the frequent and painful paracentesis procedures many of these patients currently require.

BIV201 is being developed with the goal of alleviating the portal hypertension

and correcting splanchnic vasodilation, thereby increasing effective blood volume and reducing the signals to the kidneys to

retain excess salt and water.

If successful, BIV201 could halt the cycle of accelerating fluid generation in ascites patients and reduce

the need for the frequent and painful paracentesis procedures many of these patients currently require.

Future Possible BIV201 Indications

Based on international investigative studies of the active agent in

BIV201, terlipressin, our new drug candidate has potential future applications in other life-threatening conditions due to liver cirrhosis,

such as those listed below.

Based on international investigative studies of the active agent in BIV201,

terlipressin, our new drug candidate has potential future applications in other life-threatening conditions due to liver cirrhosis, such

as those listed below.

Securing marketing approvals for any of these new uses will require well-controlled clinical trials to satisfy

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Bleeding Esophageal Varices (BEV):

The bursting of blood vessels

lining the esophagus due to high blood pressure (portal hypertension) in the vein which supplies blood to the liver resulting

as a result of advanced liver cirrhosis.

The bursting of blood vessels lining the esophagus due to high blood pressure (“portal hypertension”) in the vein which supplies blood to the liver resulting as a result of advanced liver cirrhosis.

This situation requires emergency treatment to avoid blood loss and death.

Hepatorenal Syndrome-Acute Kidney Injury (HR/S-AKI):

As liver cirrhosis and ascites progress, the patients

kidneys may begin to fail, and this deadly condition may set in.

It often occurs once a patient no longer responds to (off-label) drugs

used to control ascites.

Treatment of HRS-AKI requires hospitalization as multiple organ failure and death may occur, typically within

2-4 weeks absent liver transplant.

As liver cirrhosis and ascites progress, the patients’ kidneys may begin to fail, and this deadly condition may set in.

It often occurs once a patient no longer responds to (off-label) drugs used to control ascites.

Treatment of HRS-AKI requires hospitalization as multiple organ failure and death may occur, typically within 2-4 weeks absent liver transplant.

We obtained Orphan Drug designation for BIV201 in the U.S.

for the treatment of HRS on November 21, 2018.

In May 2021, BioVie submitted a Type B Meeting Package to the FDA seeking to conduct a single pivotal US Phase 3 clinical trial

in the treatment of HRS-AKI.

In May 2021, BioVie submitted a Type B Meeting Package to the FDA seeking to conduct a single pivotal US Phase 3 clinical trial in the treatment of HRS-AKI.

In June 2021, we received FDA feedback on the proposed trial design.

We are currently finalizing the trial

protocol and statistical analysis plan based on their guidance, and plan to commence the trial late this year.

Agreement was reached on the key elements of a Phase 3 trial in the Preliminary Meeting Comments received from the FDA on April 15, 2022 in response to a subsequent Type C meeting request.

Neurodegenerative Disease Program

In June 2021, BioVie purchased the assets of NeurMedix, Inc., a privately

held clinical-stage biopharmaceutical company focused on developing novel therapeutic products for the treatment of neurodegenerative

and neurological disorders and certain cancers.

NeurMedix was formed in November 2014 to acquire and commercialize intellectual property

and know-how.

In December 2014, NeurMedixs parent entity purchased all the assets related to NE3107 from Harbor Therapeutics, Inc.

and these assets were transferred to NeurMedix in February 2015.

NE3107 is believed to be a selective inhibitor of inflammatory ERK signaling

that reduces neuroinflammation.

It is an orally administered potentially first-in-class small molecule that may 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 play fundamental roles in the development of Alzheimers and Parkinsons Disease,

and NE3107 could, if approved, represent an entirely new medical approach to treating these devastating conditions.

The FDA has authorized

a potentially pivotal Phase 3 randomized, double-blind, placebo-controlled, parallel group, multicenter study to evaluate NE3107 in subjects

who have mild to moderate Alzheimers disease (NCT04669028).

BioVie acquired the biopharmaceutical assets of NeurMedix, Inc., a privately

held clinical-stage pharmaceutical company and related party affiliate, in June 2021.

The acquired assets include NE3107, a potentially

selective inhibitor of inflammatory ERK signaling that, based on animal studies, is believed to reduce neuroinflammation.

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 and Parkinson’s Disease, and NE3107 could, if approved, represent an entirely

new medical approach to treating these devastating conditions affecting an estimated 6 million Americans suffering from Alzheimer’s

and 1 million from Parkinson’s.

The FDA has authorized a potentially pivotal Phase 3 randomized, double-blind, placebo-controlled,

parallel group, multicenter study to evaluate NE3107 in subjects who have mild to moderate Alzheimer’s disease (NCT04669028).

initiated this trial on August 5, 2021 and are targeting primary completion in mid calendar year of 2023.

Alzheimer’s Disease

Alzheimers disease (AD), which affects an estimated 6 million

Americans, is a neuroinflammatory and neurodegenerative condition characterized by progressive deterioration of cognitive function and

loss of short-term memory and executive function.

Alzheimer’s disease (AD), which affects an estimated 6 million Americans,

is a neuroinflammatory and neurodegenerative condition characterized by progressive deterioration of cognitive function and loss of short-term

memory and executive function.

Cognitive tests quantifying AD severity have been exhaustively developed.

Formal diagnosis

of AD has historically been dependent on the presence of extraneuronal amyloid beta (A β )

plaques, which can only be observed at autopsy or with the aid of sophisticated radioimaging techniques.

However, diagnostic methods have

recently been approved that quantify A β in peripheral blood and correlate well

with imaging results.

Formal diagnosis of AD has historically

been dependent on the presence of extraneuronal amyloid beta (A β ) plaques,

which can only be observed at autopsy or with the aid of sophisticated radioimaging techniques.

However, diagnostic methods have recently

been approved that quantify A β in peripheral blood and correlate well with

imaging results.

A β plaques can also be found in people without apparent

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these factors and cognitive impairment are described by relatively new terms, type 3 diabetes and metabolic-cognitive syndrome.

A large body of evidence supports inflammation as a primary driver

of pathology in AD.

The major inflammation signaling node, NFkB, and the cytokine tumor necrosis factor (TNF) are important initiators

of inflammatory signaling in AD pathology.

NE3107 is believed to inhibit extracellular signal regulated kinase (ERK)/NFkB activation and

TNF production stimulated by inflammatory mediators, such as lipopolysaccharide.

Inhibition of NFkB activation and TNF production from

this type of stimulation has broad potential implications for reduction of pathological peripheral and central nervous system (CNS) inflammatory

signaling in AD, which include reduction of inflammation-driven insulin resistance, decreased inflammatory cell infiltration into the

CNS, and decreased microglia activation.

Reduction of systemic inflammation and inflammation driven insulin resistance are also predicted

to have beneficial effects on hypothalamus-pituitary-adrenal (HPA) axis dysregulation and hippocampal dysregulation of cortisol secretion

that are consequences of adipose inflammation and insulin resistance, and known to promote cognitive impairment, and are also forward-feeding

for insulin resistance.

Inflammation, insulin resistance, and associated

metabolic dysregulation in the brain contribute to A β oligomerization and aggregation,

A large body of evidence supports inflammation as a primary driver of pathology

The major inflammation signaling node, NFkB, and the cytokine tumor necrosis factor (TNF) are important initiators of inflammatory

signaling in AD pathology.

NE3107 is believed to inhibit extracellular signal regulated kinase (ERK)/NFkB activation and TNF production

stimulated by inflammatory mediators, such as lipopolysaccharide.

Inhibition of NFkB activation and TNF production from this type of stimulation

has broad potential implications for reduction of pathological peripheral and central nervous system (CNS) inflammatory signaling in AD,

which include reduction of inflammation-driven insulin resistance, decreased inflammatory cell infiltration into the CNS, and decreased

microglia activation.

Reduction of systemic inflammation and inflammation driven insulin resistance are also predicted to have beneficial

effects on hypothalamus-pituitary-adrenal (HPA) axis dysregulation and hippocampal dysregulation of cortisol secretion that are consequences

of adipose inflammation and insulin resistance, and known to promote cognitive impairment, and are also forward-feeding for insulin resistance.

Inflammation, insulin resistance, and associated metabolic

dysregulation in the brain contribute to A β oligomerization and aggregation,

phospho-tau formation, reduced neuron survival stimulus, and a forward-feeding cycle of neuronal energy deficit and oxidative stress,

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sensitizing activity has the potential to disrupt this forward-feeding cycle of AD pathology.

Insulin has a major role in metabolic regulation and neuron survival,

while insulin resistance and T2D are closely linked to AD pathology.

Insulin signaling is involved in synaptic plasticity, learning, and

Insulin has a major role in metabolic regulation and neuron survival, while

insulin resistance and T2D are closely linked to AD pathology.

Insulin signaling is involved in synaptic plasticity, learning, and memory.

Exogenous insulin enhances cognition in normal and cognitively impaired subjects.

Insulin resistance is linked to cognitive impairment.

The multifactorial influence of insulin signaling on neuron survival

and cognition suggests that correction of insulin signaling deficits in the target population may provide significant benefits

The multifactorial influence of insulin signaling on neuron survival and

cognition suggests that correction of insulin signaling deficits with NE3107 in the target population may provide significant benefits

on both cognition and disease progression.

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work showing peripheral insulin resistance promotes insulin resistance and senescence in the CNS.

There is also extensive literature on the complex role of adipose

tissue inflammation in systemic inflammation, insulin resistance, hypothalamus-pituitary-adrenal axis (HPA) dysregulation and chronic

cortisol excess in cognitive impairment in AD.

Obesity and inflammation are closely linked in expanding adipose tissue, where the production

of inflammatory cytokines and increased cortisol are driven though up-regulation of 11 β -hydroxysteroid

There is also an extensive literature on the complex role of adipose tissue

inflammation in systemic inflammation, insulin resistance, hypothalamus-pituitary-adrenal axis (HPA) dysregulation and chronic cortisol

excess in cognitive impairment in AD.

Obesity and inflammation are closely linked in expanding adipose tissue, where the production of

inflammatory cytokines and increased cortisol are driven though up-regulation of 11 β -hydroxysteroid

dehydrogenase type 1 and adipocyte mineralocorticoid receptor activation.

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of inflammation and HPA-hippocampal dysregulation.

Systemic inflammation from inflamed adipose and associated mononuclear cells, promotes CNS inflammation with associated

cognitive decline and neurodegeneration.

A therapy with anti-inflammatory activity against systemic/adipose inflammation and factors

that dysregulate cortisol secretion, such as hyperglycemia, has the potential to decrease cognitive impairment and neurodegenerative

mechanisms that have been linked to cortisol excess.

Systemic inflammation from inflamed adipose and associated mononuclear

cells, promotes CNS inflammation with associated cognitive decline and neurodegeneration.

NE3107’s anti-inflammatory activity against

systemic/adipose inflammation and factors that dysregulate cortisol secretion, such as hyperglycemia, has the potential to decrease cognitive

impairment and neurodegenerative mechanisms that have been linked to cortisol excess.

Parkinson’s Disease

Neuroinflammation and activation of brain microglia, leading to increased proinflammatory cytokines (particularly

tumor necrosis factor (TNF)) play a pivotal role in Parkinsons Disease (PD), which affects an estimated 1 million Americans.

administration of levodopa (converted to dopamine in the brain) is the current standard of care treatment for this movement disorder,

but prolonged daily administration often leads to side effects of uncontrolled movements called levodopa-induced dyskinesia, commonly

referred to as LID.

The Company initiated a study by treating the first patient, in its Phase

2 study assessing NE3107’s safety and tolerability and potential pro-motoric impact in Parkinson’s disease patients on January

The NM201 study (NCT05083260) is a double-blind, placebo-controlled, safety, tolerability, and pharmacokinetics study in Parkinson’s

Disease (PD).

Participants will be treated with carbidopa/levodopa and NE3107 or placebo.

Forty patients with a defined PD medication “off state” will

be randomized 1:1 placebo to active NE3107 20 mg twice daily for 28 days.

Safety assessments will look at standard measures of patient

health and potential for drug-drug interactions affecting L-dopa pharmacokinetics and activity.

Exploratory efficacy assessments will

use the Motor Disease Society Unified Parkinson’s Disease Rating (MDS-UPDRS) parts 1-3, ON/OFF Diary, and Non-Motor Symptom Scale.

Neuroinflammation and activation of brain microglia, leading to increased

proinflammatory cytokines (particularly TNF) which play a pivotal role in Parkinson’s Disease (PD), which affects an estimated 1

million Americans.

Daily administration of levodopa (converted to dopamine in the brain) is the current standard of care treatment for

this movement disorder, but prolonged daily administration leads to side effects of uncontrolled movements called levodopa-induced dyskinesia,

commonly referred to as LID.

Recent evidence demonstrates that daily administration of levodopa further increases neuroinflammation, microglia

activation, and TNF inflammatory damage in neurons.

We have observed that in a mouse model of PD, NE3107 decreased inflammation and TNF in the brain and increased

neuron survival (Nicoletti, 2012 Parkinson’s Disease 969418.) In this neurotoxin induced model, NE3107 decreased clinical signs

of disease and neuronal death compared to placebo treated mice.

We have shown in a mouse model that PD NE3107 decreases inflammation and

TNF in the brain and increases neuron survival (Nicoletti, 2012 Parkinson’s Disease 969418.) In this neurotoxin induced model, NE3107

decreased clinical signs of disease and neuronal death compared to placebo treated mice.

An unpublished study in a neurotoxin induced marmoset model of Parkinson’s

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if true could enable a straightforward clinical development strategy to test NE3107 in PD patients needing promotoric therapy.

If approved as a promotoric agent, NE3107 could provide a non-dopaminergic

If approved as a promotoric agent, NE3107 would provide a non-dopaminergic

alternative to Parkinson’s patients, and an opportunity to significantly delay the need to start levodopa therapy.

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a slowing of disease progression, the most important and still unmet objective of PD drug development.

In certain types of cancers, inflammatory cell signaling is at the

heart of disease progression.

NE3107 has been observed to decrease inflammatory cell signaling in vitro, in animal models and in human

clinical trials.

Recently, evidence has developed that cancers are dependent on inflammatory cell signaling, not only in the tumor cells,

but also in immune, stromal and hematopoietic cells in the tumor microenvironment.

The inflammatory pathways that have been elucidated in non-cancerous

cells in the tumor microenvironment are similar to those NE3107 decrease in inflammatory cells in metabolic disorders and neurodegeneration.

BioVie is developing clinical trial-enabling data for Multiple Myeloma and Prostate cancers.

Intellectual Property

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We also filed a PCT application covering our novel liquid formulations of terlipressin (international patent application PCT/US2020/034269,

published as WO2020/237170) and we will seek patent protection in at least the United States, Europe, China and Japan.

In April 2020,

we elected certain claims in our pending U.S.

patent application 16/379,446 (a continuation application related to the 945 Patent,

which was canceled pursuant to an inter partes review proceeding, discussed above).

In addition, we have applied for patent coverage

for a method of treating ascites with BIV201 in Japan, Europe, China and Hong Kong.

published as WO2020/237170) and are seeking patent protection in at least the United States, Europe, China, Japan and other jurisdictions.

Also, we own U.S.

Patent 11,364,277, which is directed to a method of treating ascites with BIV201, and we are pursuing similar patent

coverage in Japan, Europe, and China.

As of August 22, 2022, we have fifteen (15) issued U.S.

(1) pending U.S.

patents, one (1)

patent application, one (1) pending U.S.

provisional application (provisional application filed May 18, 2021) and six

(6) issued foreign patents directed to protecting NE3107 and related compounds and methods of making and using thereof.

and pending patent applications and their expiration dates are provided below.

PCT application and six (6) issued foreign patents directed to protecting NE3107

and related compounds and methods of making and using thereof.

patents and pending patent applications and their projected expiration

dates are provided below.

Patent Application

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Compositions for Treatment of Neurodegenerative Conditions

* Foreign counterparts issued in Australia, Canada, Europe and

South Korea expire 4/3/2029.

PCT/US2022/027294

Foreign counterparts issued in Australia, Canada, Europe and South Korea expire 4/3/2029.

Foreign counterparts issued in Europe and Japan expire 6/5/2029.

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

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,

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United States Drug Development Process

In the United States, the FDA regulates drugs under the Federal Food,

Drug and Cosmetic Act, or FDCA, and implementing regulations.

In the United States, the FDA regulates drugs under the Federal Food, Drug

and Cosmetic Act, or FDCA, and implements regulations.

Drugs are also subject to other federal, state and local statutes and regulations.

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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:

● Completion of preclinical laboratory tests, animal studies

and formulation studies according to Good Laboratory Practices or other applicable regulations;

● Submission to the FDA of an Investigational New Drug Application,

or an IND, which must become effective before human clinical trials may begin;

● Performance of adequate and well-controlled human clinical

trials according to the FDAs current good clinical practices, or GCPs, to establish the safety and efficacy of the proposed drug or

biologic for its intended use;

● Submission to the FDA of a New Drug Application, or an NDA,

for a new drug product, or a Biologics License Application, or a BLA, for a new biological product;

● Satisfactory completion of an FDA inspection of the manufacturing

facility or facilities where the drug or biologic is to be produced to assess compliance with the FDAs current good manufacturing practice

standards, or cGMP, to assure that the facilities, methods and controls are adequate to preserve the drugs or biologics identity, strength,

quality and purity;

● Potential FDA audit of the nonclinical and clinical trial sites

that generated the data in support of the NDA or BLA;

The process required by the FDA before a drug or biological product may

be marketed in the United States generally involves the following:

Completion of preclinical laboratory tests, animal studies and formulation studies according to Good Laboratory Practices or other applicable regulations;

Submission to the FDA of an Investigational New Drug Application, or an IND, which must become effective before human clinical trials may begin;

Performance of adequate and well-controlled human clinical trials according to the FDA’s current good clinical practices, or GCPs, to establish the safety and efficacy of the proposed drug or biologic for its intended use;

Submission to the FDA of a New Drug Application, or an NDA, for a new drug product, or a Biologics License Application, or a BLA, for a new biological product;

Satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the drug or biologic is to be produced to assess compliance with the FDA’s current good manufacturing practice standards, or cGMP, to assure that the facilities, methods and controls are adequate to preserve the drug’s or biologic’s identity, strength, quality and purity;

Potential FDA audit of the nonclinical and clinical trial sites that generated the data in support of the NDA or BLA;

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 sponsors control.

Clinical trials are conducted under protocols detailing, among other

things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria, and the parameters to be used

to monitor subject safety.

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 selection 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 FDAs good clinical practices requirements.

Clinical trials must be conducted in accordance with the

FDA’s good clinical practices requirements.

Further, each clinical trial must be reviewed and approved by an independent institutional

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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:

The drug or biologic is initially

introduced into healthy human subjects and tested for safety, dosage tolerance, absorption, metabolism, distribution and excretion.

the case of some products for severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically

administer to healthy volunteers, the initial human testing is often conducted in patients having the specific disease.

The drug or biologic is evaluated

in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the

product for specific targeted diseases and to determine dosage tolerance, optimal dosage and dosing schedule for patients having the

specific disease.

Clinical trials are undertaken

to further evaluate dosage, clinical efficacy and safety in an expanded patient population at geographically dispersed clinical trial

These clinical trials, which usually involve more subjects than earlier trials, are intended to establish the overall risk/benefit

ratio of the product and provide an adequate basis for product labeling.

Generally, at least two adequate and well-controlled Phase 3

clinical trials are required by the FDA for approval of an NDA or BLA.

Human clinical trials prior to approval are typically conducted in three

sequential phases that may overlap or be combined:

The drug or biologic is initially introduced into healthy human subjects and tested for safety, dosage tolerance, absorption, metabolism, distribution and excretion.

In the case of some products for severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing is often conducted in patients having the specific disease.

The drug or biologic is evaluated in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance, optimal dosage and dosing schedule for patients having the specific disease.

Clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population at geographically dispersed clinical trial sites.

These clinical trials, which usually involve more subjects than earlier trials, are intended to establish the overall risk/benefit ratio of the product and provide an adequate basis for product labeling.

Generally, at least two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval of an NDA or BLA.

Post-approval studies, or Phase 4 clinical trials, may be conducted

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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 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 IRBs requirements or if the drug

or biologic has been associated with unexpected serious harm to patients.

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

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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.

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.

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

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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.

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.

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in the submission and often will request additional testing or information.

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

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 data and information.

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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.

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

Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review and approval

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.

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.

however, may receive approval of different products for the indication for which the Orphan product has exclusivity or obtain approval

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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.

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

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.

designation, priority review and accelerated approval do not change the standards for approval but may expedite the development or approval

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.

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

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

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

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that could otherwise restrict the distribution or use of the product.

business is managed by our officers.

The Companys Chairman, Terren Peizer, served as Chief Executive Officer from July 2018 and

devoted his part-time efforts to the Companys activities through April 27, 2021.

On April 27, 2021, the board of directors appointed

Cuong Do as Chief Executive Officer & President.

Wendy Kim, our Chief Financial Officer and Corporate Secretary;

Adams, who previously served as President and Chief Operating Officer, serving as our Companys Executive Vice President –

Liver Cirrhosis Programs;

and Penelope Markham, PhD, Executive Vice President - Liver Cirrhosis R&D;

devote their full-time efforts

to the Company activities.

Our business is managed by our officers who consist of Mr.

Cuong Do, Chief

Executive Officer & President;

Dr Joseph M Columbo, Chief Medical Officer, who joined the Company on November 1, 2021;

and Wendy Kim,

our Chief Financial Officer and Corporate Secretary;

along with Penelope Markham, PhD, Executive Vice President - Liver Cirrhosis R&D;

Chris Reading, PhD, Executive Vice President - Neuroscience R&D;

and Clarence Alhem, Executive Vice President

- Neuroscience Product Development began their employment with the Company on July 1, 2021 and devotes their full-time efforts to the

Companys Neuroscience programs.

We also rely on a team of highly experienced scientific, medical, and regulatory consultants to

conduct its product development activities.

and Clarence Ahlem, Executive Vice President - Neuroscience Product

These individuals devote their full-time efforts to the Company activities.

The company has 13 employees which are all full

We also rely on a team of highly experienced scientific, medical, and regulatory consultants to conduct its product development

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business