What changed in this filing

/stocks — the workspaceLOADING

Item 2. Management’s Discussion and Analysis

2022-02-09 compared with 2021-08-12 · 706 added, 712 removed, 108 unchanged (93% of the section changed)

1 unchanged sentence

Forward-Looking Statements

This Quarterly Report on Form 10-Q includes

This Quarterly Report on Form 10-Q includes forward-looking

All statements other than statements of historical facts contained in this Quarterly Report on Form 10-Q, including statements

regarding our anticipated future clinical and regulatory milestone events, future financial position, business strategy and plans and

objectives of management for future operations, are forward-looking statements.

The words “believe,” “may,” “estimate,”

“continue,” “anticipate,” “intend,” “expect” “should,” “forecast,”

“could,” “suggest,” “plan” and similar expressions, as they relate to us, are intended to identify

forward-looking statements.

All statements other than statements of historical facts contained in this Quarterly Report on Form

10-Q, including statements regarding our anticipated future clinical and regulatory milestone events, future financial position,

business strategy and plans and objectives of management for future operations, are forward-looking statements.

The words “believe,”

“may,” “estimate,” “continue,” “anticipate,” “intend,” “expect”

“should,” “forecast,” “could,” “suggest,” “plan” and similar expressions,

as they relate to us, are intended to identify forward-looking statements.

Such forward-looking statements include, without limitation,

statements regarding:

volatility in our stock and

in the markets in general;

our ability to successfully

conduct clinical and preclinical trials for our product candidates;

our ability to raise additional

capital on favorable terms and the impact of such activities on our stockholders and stock price;

the impact of the COVID-19

outbreak and its effect on us;

our ability to generate any

revenue or to continue as a going concern;

our ability to execute our

research and development plan on time and on budget;

our products ability to demonstrate

efficacy or an acceptable safety profile of our product candidates;

our ability to obtain the support

of qualified scientific collaborators;

our ability, whether alone

or with commercial partners, to successfully commercialize any of our product candidates that may be approved for sale;

our ability to identify and

obtain additional product candidates;

our reliance on third parties

in non-clinical and clinical studies;

our ability to defend against

product liability claims;

our ability to safeguard against

security breaches;

our ability to obtain and maintain

sufficient intellectual property protection for our product candidates;

our ability to comply with

our intellectual property licensing agreements;

our ability to defend against

claims of intellectual property infringement;

our ability to comply with

the maintenance requirements of the government patent agencies;

our ability to protect our

intellectual property rights throughout the world;

the anticipated start dates,

durations and completion dates of our ongoing and future clinical studies;

the anticipated designs of

our future clinical studies;

the impact of fast track designation

on receipt of actual FDA approval;

our anticipated future regulatory

submissions and our ability to receive regulatory approvals to develop and market our product candidates, including any orphan drug or

fast track designations;

our anticipated future cash

We have based these forward-looking statements

largely on our current expectations and projections about future events, including the responses we expect from the U.S.

Drug Administration, (“FDA”), and other regulatory authorities and financial trends that we believe may affect our

financial condition, results of operations, business strategy, preclinical and clinical trials, and financial needs.

These forward-looking

statements are subject to a number of risks, uncertainties and assumptions including without limitation the risks described in

“Risk Factors” in Part I, Item 1A of our Annual Report on Form 10-K filed with the Securities and Exchange Commission

on December 28, 2020.

These risks are not exhaustive.

Other sections of this Quarterly Report on Form 10-Q include additional factors

which could adversely impact our business and financial performance.

Moreover, we operate in a very competitive and rapidly changing

New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, nor

can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause

actual results to differ materially from those contained in any forward-looking statements.

You should not rely upon forward-looking

statements as predictions of future events.

We cannot assure you that the events and circumstances reflected in the forward-looking

statements will be achieved or occur and actual results could differ materially from those projected in the forward-looking statements.

Except as required by applicable laws including the securities laws of the United States, we assume no obligation to update or

supplement forward-looking statements.

As used in this Quarterly Report on Form 10-Q,

the terms “we,” “us,” “our,” and “Anavex” mean Anavex Life Sciences Corp., unless

the context clearly requires otherwise.

Such forward-looking statements include, without limitation, statements regarding:

in our stock and in the markets in general;

ability to successfully conduct clinical and preclinical trials for our product candidates;

ability to raise additional capital on favorable terms and the impact of such activities on our stockholders and stock price;

impact of the COVID-19 outbreak and its effect on us;

ability to generate any revenue or to continue as a going concern;

ability to execute our research and development plan on time and on budget;

products ability to demonstrate efficacy or an acceptable safety profile of our product candidates;

ability to obtain the support of qualified scientific collaborators;

ability, whether alone or with commercial partners, to successfully commercialize any of our product candidates that may be approved

ability to identify and obtain additional product candidates;

reliance on third parties in non-clinical and clinical studies;

ability to defend against product liability claims;

ability to safeguard against security breaches;

ability to obtain and maintain sufficient intellectual property protection for our product candidates;

ability to comply with our intellectual property licensing agreements;

ability to defend against claims of intellectual property infringement;

ability to comply with the maintenance requirements of the government patent agencies;

ability to protect our intellectual property rights throughout the world;

anticipated start dates, durations and completion dates of our ongoing and future clinical studies;

anticipated designs of our future clinical studies;

impact of fast track designation on receipt of actual FDA approval;

anticipated future regulatory submissions and our ability to receive regulatory approvals to develop and market our product candidates,

including any orphan drug or fast track designations;

anticipated future cash position.

We have based these forward-looking statements largely

on our current expectations and projections about future events, including the responses we expect from the U.S.

Food and Drug Administration,

(“FDA”), and other regulatory authorities and financial trends that we believe may affect our financial condition, results

of operations, business strategy, preclinical and clinical trials, and financial needs.

These forward-looking statements are subject to

a number of risks, uncertainties and assumptions including without limitation the risks described in “Risk Factors” in Part

I, Item 1A of our Annual Report on Form 10-K filed with the Securities and Exchange Commission on November 24, 2021.

These risks are not

Other sections of this Quarterly Report on Form 10-Q include additional factors which could adversely impact our business

and financial performance.

Moreover, we operate in a very competitive and rapidly changing environment.

New risk factors emerge from time

to time and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business

or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any

forward-looking statements.

You should not rely upon forward-looking statements as predictions of future events.

We cannot assure you

that the events and circumstances reflected in the forward-looking statements will be achieved or occur and actual results could differ

materially from those projected in the forward-looking statements.

Except as required by applicable laws including the securities laws

of the United States, we assume no obligation to update or supplement forward-looking statements.

As used in this Quarterly Report on Form 10-Q, the

terms “we,” “us,” “our,” and “Anavex” mean Anavex Life Sciences Corp., unless the context

clearly requires otherwise.

Our Current Business

Anavex Life Sciences Corp.

is a clinical stage

biopharmaceutical company engaged in the development of differentiated therapeutics by applying precision medicine to central nervous

system (“CNS”) diseases with high unmet need.

We analyze genomic data from clinical studies to identify biomarkers,

which we use to select patients that will receive the therapeutic benefit for the treatment of neurodegenerative and neurodevelopmental

Our lead compound, ANAVEX ® 2-73,

is being developed to treat Alzheimer’s disease, Parkinson’s disease and potentially other central nervous system diseases,

including rare diseases, such as Rett syndrome, a rare severe neurological monogenic disorder caused by mutations in the X-linked

gene, methyl-CpG-binding protein 2 (“MECP2”).

We currently have two core programs and two

seed programs.

Our core programs are at various stages of clinical and preclinical development, in neurodegenerative and neurodevelopmental

The following table summarizes key information about our programs:

Anavex has a portfolio of compounds varying

in sigma-1 receptor (S1R) binding activities.

The SIGMAR1 gene encodes the S1R protein, which is an intracellular chaperone protein

with important roles in cellular communication.

S1R is also involved in transcriptional regulation at the nuclear envelope and

restores homeostasis and stimulates recovery of cell function when activated.

In order to validate the ability of our compounds

to activate quantitatively the S1R, we performed, in collaboration with Stanford University, a quantitative Positron Emission Tomography

(PET) imaging scan in mice, which demonstrated a dose-dependent ANAVEX ® 2-73 target engagement or receptor occupancy

(RO) with S1R in the brain.

is a clinical stage biopharmaceutical

company engaged in the development of differentiated therapeutics by applying precision medicine to central nervous system (“CNS”)

diseases with high unmet need.

We analyze genomic data from clinical studies to identify biomarkers, which we use to select patients that

will receive the therapeutic benefit for the treatment of neurodegenerative and neurodevelopmental diseases.

Our lead compound, ANAVEX ® 2-73, is

being developed to treat Alzheimer’s disease, Parkinson’s disease and potentially other central nervous system diseases, including

rare diseases, such as Rett syndrome, a rare severe neurological monogenic disorder caused by mutations in the X-linked gene, methyl-CpG-binding

protein 2 (“MECP2”).

We currently have two core programs and two seed programs.

Our core programs are at various stages of clinical and preclinical development, in neurodegenerative and neurodevelopmental diseases.

The following table summarizes key information about our

* = Orphan Drug Designation by the FDA;

lines indicate planned clinical studies

Anavex has a portfolio of compounds varying in sigma-1

receptor (S1R) binding activities.

The SIGMAR1 gene encodes the S1R protein, which is an intracellular chaperone protein with important

roles in cellular communication.

S1R is also involved in transcriptional regulation at the nuclear envelope and restores homeostasis and

stimulates recovery of cell function when activated.

In order to validate the ability of our compounds to activate quantitatively the

S1R, we performed, in collaboration with Stanford University, a quantitative Positron Emission Tomography (PET) imaging scan in mice,

which demonstrated a dose-dependent ANAVEX ® 2-73 target engagement or receptor occupancy (RO) with S1R in the brain.

Reyes S et al., Sci Rep.

Cellular Homeostasis

Many diseases are possibly directly caused

by chronic homeostatic imbalances or cellular stress of brain cells.

In pediatric diseases like Rett syndrome or infantile spasms,

the chronic cellular stress is possibly caused by the presence of a constant genetic mutation.

In neurodegenerative diseases, such

as Alzheimer’s and Parkinson’s diseases, chronic cellular stress is possibly caused by age-correlated buildup of cellular

insult and hence chronic cellular stress.

Specifically, defects in homeostasis of protein or ribonucleic acid (“RNA”)

lead to the death of neurons and dysfunction of the nervous system.

The spreading of protein aggregates resulting in a proteinopathy,

a characteristic finding in Alzheimer’s and Parkinson’s diseases that results from disorders of protein synthesis,

trafficking, folding, processing or degradation in cells.

The clearance of macromolecules in the brain is particularly susceptible

to imbalances that result in aggregation and degeneration in nerve cells.

For example, Alzheimer’s disease pathology is characterized

by the presence of amyloid plaques, neurofibrillary tangles, which are aggregates of hyperphosphorylated Tau protein that are a

marker of other diseases known as tauopathies as well as inflammation of microglia.

With the SIGMAR1 activation through SIGMAR1

agonists like ANAVEX ® 2-73, our approach is to restore cellular balance, i.e.

Therapies that correct

defects in cellular homeostasis might have the potential to halt or delay neurodevelopmental and neurodegenerative disease progression.

Many diseases are possibly directly caused by chronic

homeostatic imbalances or cellular stress of brain cells.

In pediatric diseases like Rett syndrome or infantile spasms, the chronic cellular

stress is possibly caused by the presence of a constant genetic mutation.

In neurodegenerative diseases, such as Alzheimer’s and

Parkinson’s diseases, chronic cellular stress is possibly caused by age-correlated buildup of cellular insult and hence chronic

cellular stress.

Specifically, defects in homeostasis of protein or ribonucleic acid (“RNA”) lead to the death of neurons

and dysfunction of the nervous system.

The spreading of protein aggregates resulting in a proteinopathy, a characteristic finding in Alzheimer’s

and Parkinson’s diseases that results from disorders of protein synthesis, trafficking, folding, processing or degradation in cells.

The clearance of macromolecules in the brain is particularly susceptible to imbalances that result in aggregation and degeneration in

For example, Alzheimer’s disease pathology is characterized by the presence of amyloid plaques, neurofibrillary tangles,

which are aggregates of hyperphosphorylated Tau protein that are a marker of other diseases known as tauopathies as well as inflammation

of microglia.

With the SIGMAR1 activation through SIGMAR1 agonists like ANAVEX ® 2-73, our approach is to restore cellular

balance, i.e.

Therapies that correct defects in cellular homeostasis might have the potential to halt or delay neurodevelopmental

and neurodegenerative disease progression.

ANAVEX ® 2-73-specific Biomarkers

A full genomic analysis of Alzheimer’s

disease (AD) patients treated with ANAVEX ® 2-73 resulted in the identification of actionable genetic variants.

significant impact of the genomic biomarkers SIGMAR1, the direct target of ANAVEX ® 2-73 and COMT, a gene involved

in memory function, on the drug response level was identified, leading to an early ANAVEX ® 2-73-specific biomarker

It is expected that excluding patients with these two identified biomarker variants (approximately 10%-20% of

the population) in prospective studies would identify approximately 80%-90% patients that would display clinically significant

improved functional and cognitive scores.

The consistency between the identified DNA

and RNA data related to ANAVEX ® 2-73, which are considered independent of AD pathology, as well as multiple endpoints

and time-points, provides support for precision medicine clinical development of ANAVEX ® 2-73 by using genetic biomarkers

identified within the study population itself to target patients who are most likely to respond to ANAVEX ® 2-73 treatment

in AD as well as indications like Parkinson’s disease dementia (PDD) or Rett syndrome (RTT) in which ANAVEX ® 2-73

A full genomic analysis of Alzheimer’s disease

(AD) patients treated with ANAVEX ® 2-73 resulted in the identification of actionable genetic variants.

A significant impact

of the genomic biomarkers SIGMAR1, the direct target of ANAVEX ® 2-73 and COMT, a gene involved in memory function, on the

drug response level was identified, leading to an early ANAVEX ® 2-73-specific biomarker hypothesis.

It is expected that

excluding patients with SIGMAR1 identified biomarker variant (approximately 10%-20% of the population) in prospective studies would

identify approximately 80%-90% patients that would display clinically significant improved functional and cognitive scores.

The consistency

between the identified DNA and RNA data related to ANAVEX ® 2-73, which are considered independent of AD pathology, as well

as multiple endpoints and time-points, provides support for precision medicine clinical development of ANAVEX ® 2-73 by using

genetic biomarkers identified within the study population itself to target patients who are most likely to respond to ANAVEX ® 2-73

treatment in AD as well as indications like Parkinson’s disease dementia (PDD) or Rett syndrome (RTT) in which ANAVEX ® 2-73

is currently studied.

5 unchanged sentences

efficacy of ANAVEX ® 2-73 in 32 patients.

ANAVEX ® 2-73 targets sigma-1 and muscarinic receptors, which

have been shown in preclinical studies to reduce stress levels in the brain believed to restore cellular homeostasis and to reverse

the pathological hallmarks observed in Alzheimer’s disease.

The Phase 2a trial demonstrated positive pharmacokinetic (PK)

and pharmacodynamic (PD) data, which established a concentration-effect relationship between ANAVEX ® 2-73 and study

measurements.

These measures obtained from all patients who participated in the entire 57 weeks include exploratory cognitive and

functional scores as well as biomarker signals of brain activity.

Additionally, the study appears to show that ANAVEX ® 2-73

activity is enhanced by its active metabolite (ANAVEX19-144), which also targets the sigma-1 receptor and has a half-life approximately

twice as long as the parent molecule.

Two consecutive trial extensions for the Phase

2a trial have allowed participants who completed the 52-week PART B of the study to continue taking ANAVEX ® 2-73,

providing an opportunity to gather extended safety data for a cumulative time period of five years.

In August 2020, patients completing

these Phase 2a trial extensions were granted continued access to treatment with ANAVEX ® 2-73 through the Australian

Government Department of Health – Therapeutic Goods Administration (TGA) compassionate use Special Access Scheme.

ANAVEX ® 2-73 targets sigma-1 and muscarinic receptors, which have

been shown in preclinical studies to reduce stress levels in the brain believed to restore cellular homeostasis and to reverse the pathological

hallmarks observed in Alzheimer’s disease.

In October 2017, we presented positive pharmacokinetic (PK) and pharmacodynamic (PD)

data from the Phase 2a study, which established a concentration-effect relationship between ANAVEX ® 2-73 and study measurements.

These measures obtained from all patients who participated in the entire 57 weeks include exploratory cognitive and functional scores

as well as biomarker signals of brain activity.

Additionally, the study appears to show that ANAVEX ® 2-73 activity is enhanced

by its active metabolite (ANAVEX19-144), which also targets the sigma-1 receptor and has a half-life approximately twice as long as the

parent molecule.

Two consecutive trial extensions for the Phase 2a

trial have allowed participants who completed the 52-week PART B of the study to continue taking ANAVEX ® 2-73, providing

an opportunity to gather extended safety data for a cumulative time period of five years.

In August 2020, patients completing these Phase

2a trial extensions were granted continued access to treatment with ANAVEX ® 2-73 through the Australian Government Department

of Health – Therapeutic Goods Administration (TGA) compassionate use Special Access Scheme.

A larger Phase 2b/3 double-blind, placebo-controlled

450-patient study of ANAVEX ® 2-73 in Alzheimer’s disease commenced in August 2018.

The Phase 2b/3 study is

a 48-week study, with participants randomized 1:1:1 to two different ANAVEX ® 2-73 doses or placebo.

The trial commenced

in Australia;

and additional regions were added in the United Kingdom, The Netherlands, Germany and Canada.

The ANAVEX ® 2-73

Phase 2b/3 study design incorporates genomic precision medicine biomarkers identified in the ANAVEX ® 2-73 Phase 2a

Primary and secondary endpoints will assess safety and both cognitive and functional efficacy, measured through Alzheimer’s

Disease Assessment Scale – Cognition (ADAS-Cog), ADCS-ADL and Clinical Dementia Rating – Sum of Boxes for cognition

and function (CDR-SB).

The study completed enrollment in June 2021, exceeding the enrollment beyond 450 patients at 52 sites across

North America, Europe and Australia.

In October 2019, we initiated a long-term open

label extension study of ANAVEX ® 2-73, entitled the ATTENTION-AD study, for patients who have completed the 48-week

Phase 2b/3 placebo-controlled trial referenced above.

This study is expected to last two years and will give patients the opportunity

to continue their treatment.

study of ANAVEX ® 2-73 in Alzheimer’s disease commenced in August 2018.

The Phase 2b/3 study enrolled 509 patients

for 48 weeks, randomized 1:1:1 to two different ANAVEX ® 2-73 doses or placebo.

The trial commenced in Australia;

fiscal 2020 additional regions were added in the United Kingdom, The Netherlands, Germany and Canada.

The ANAVEX ® 2-73 Phase

2b/3 study design incorporates genomic precision medicine biomarkers identified in the ANAVEX ® 2-73 Phase 2a study.

and secondary endpoints will assess safety and both cognitive and functional efficacy, measured through Alzheimer’s Disease Assessment

Scale – Cognition (ADAS-Cog), ADCS-ADL and Clinical Dementia Rating – Sum of Boxes for cognition and function (CDR-SB).

study completed enrollment in June 2021, exceeding the 450 patient enrollment target at 52 sites across North America, Europe and Australia.

In October 2019, we initiated a long-term open label

extension study of ANAVEX ® 2-73, entitled the ATTENTION-AD study, for patients who have completed the 48-week Phase 2b/3

placebo-controlled trial referenced above.

This study is expected to last two years and will give patients the opportunity to continue

their treatment.

Upon request by patients, caretakers and investigators, this extension study was extended by one further year.

Rett Syndrome

1 unchanged sentence

data for ANAVEX ® 2-73 in Rett syndrome, a rare neurodevelopmental disease.

The study was funded by the International

Rett Syndrome Foundation (“Rettsyndrome.org”).

In January 2017, we were awarded a financial grant from Rettsyndrome.org

of a minimum of $0.6 million to cover some of the costs of a multicenter Phase 2 clinical trial of ANAVEX ® 2-73 for

the treatment of Rett syndrome.

The study was funded by the International Rett

Syndrome Foundation (“Rettsyndrome.org”).

In January 2017, we were awarded a financial grant from Rettsyndrome.org of a minimum

of $0.6 million to cover some of the costs of a multicenter Phase 2 clinical trial of ANAVEX ® 2-73 for the treatment of

Rett syndrome.

This award was received in quarterly instalments which commenced during fiscal 2018.

In March 2019, we commenced the first Phase

2 clinical trial in a planned Rett syndrome program of ANAVEX ® 2-73 for the treatment of Rett syndrome.

are being conducted in a range of patient age demographics and geographic regions, utilizing a convenient oral liquid once-daily

formulation of ANAVEX ® 2-73.

The first Phase 2 study, which took place in

the United States, was completed in December 2020.

This trial was a randomized double-blind, placebo-controlled safety, tolerability,

pharmacokinetic and efficacy study of oral liquid ANAVEX ® 2-73 formulation in 25 adult female patients with Rett

syndrome over a 7-week treatment period including ANAVEX ® 2-73-specific genomic precision medicine biomarkers.

primary endpoint of the trial was safety.

The dosing of 5 mg ANAVEX ® 2-73 was well-tolerated and demonstrated dose-proportional

PK (pharmacokinetics).

All secondary efficacy endpoints of the trial showed statistically significant and clinically meaningful,

drug exposure-dependent response in the Rett Syndrome Behaviour Questionnaire (RSBQ) Total scores, when compared to placebo, in

the ITT cohort (all participants, p = 0.048).

66.7% of ANAVEX ® 2-73 treated subjects showed a statistically significant

improvement in drug exposure-dependent RSBQ response as compared to 10% of the subjects on placebo in the ITT cohort (all participants,

ANAVEX ® 2-73 treatment resulted in a sustained improvement in Clinical Global Impression Improvement

(CGI-I) scores throughout the 7-week study, when compared to placebo in the ITT cohort (all participants, p = 0.014).

ANAVEX ® 2-73 treated subjects showed a statistically significant CGI-I response, defined as sustained improvement

to treatment, as compared to 40% of the subjects on placebo in the ITT cohort (all participants, p = 0.014).

Consistent with previous

ANAVEX ® 2-73 clinical trials, patients carrying the common form of the SIGMAR1 gene treated with ANAVEX ® 2-73

experienced stronger improvements in the prespecified efficacy endpoints.

The second Phase 2 study of ANAVEX ® 2-73

for the treatment of Rett syndrome, called the AVATAR study, commenced in June 2019.

This study is taking place in Australia and

the United Kingdom using a higher dose than the U.S.

based Phase 2 study for Rett syndrome.

The study will evaluate the safety

and efficacy of ANAVEX ® 2-73 in approximately 33 patients over a 7-week treatment period including ANAVEX ® 2-73

specific precision medicine biomarkers.

All patients who participate in the study will be eligible to receive ANAVEX ® 2-73

under a voluntary open label extension protocol.

In July 2020, we commenced the third study

of ANAVEX ® 2-73 for the treatment of Rett syndrome, called the EXCELLENCE study.

This Phase 2/3 study in pediatric

patients with Rett syndrome will evaluate the safety and efficacy of ANAVEX ® 2-73 in at least 69 pediatric patients,

aged 5 to 18, over a 12-week treatment period incorporating ANAVEX ® 2-73 specific precision medicine biomarkers.

All patients who participate in the study will be eligible to receive ANAVEX ® 2-73 under a voluntary open label extension

In March 2019, we commenced the first Phase 2 clinical

trial in a planned Rett syndrome program of ANAVEX ® 2-73 for the treatment of Rett syndrome.

The studies will be conducted

in a range of patient age demographics and geographic regions, utilizing a convenient oral liquid once-daily formulation of ANAVEX ® 2-73.

The first Phase 2 study, (ANAVEX®2-73-RS-001), which took place in the

United States, was completed in December 2020.

This trial was a randomized double-blind, placebo-controlled safety, tolerability, pharmacokinetic

and efficacy study of oral liquid ANAVEX ® 2-73 formulation in 25 adult female patients with Rett syndrome over a 7-week

treatment period including ANAVEX ® 2-73-specific genomic precision medicine biomarkers.

The primary endpoint of the trial

The dosing of 5 mg ANAVEX ® 2-73 was well-tolerated and demonstrated dose-proportional PK (pharmacokinetics).

All secondary efficacy endpoints of the trial showed statistically significant and clinically meaningful response in the Rett Syndrome

Behaviour Questionnaire (RSBQ AUC) Total scores, when compared to placebo, in the ITT cohort (all participants, p = 0.011).

66.7% of ANAVEX ® 2-73

treated subjects showed a statistically significant improvement in RSBQ response as compared to 10% of the subjects on placebo in the

ITT cohort (all participants, p = 0.011).

ANAVEX ® 2-73 treatment resulted in a sustained improvement in Clinical Global

Impression Improvement (CGI-I) scores throughout the 7-week study, when compared to placebo in the ITT cohort (all participants, p = 0.014).

Consistent with previous ANAVEX ® 2-73 clinical trials, patients carrying the common form of the SIGMAR1 gene treated with

ANAVEX ® 2-73 experienced stronger improvements in the prespecified efficacy endpoints.

second, international study of ANAVEX ® 2-73 for the treatment of Rett syndrome, called the AVATAR study, commenced in June

This study took place in Australia and the United Kingdom using a higher dose than the U.S.

based Phase 2 study for Rett

The study was a Phase 3 randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of ANAVEX ® 2-73

in 33 patients over a 7-week treatment period including ANAVEX ® 2-73 specific precision medicine biomarkers.

Following the

successful completion of the U.S.

Phase 2 Rett syndrome study (ANAVEX®2-73-RS-001), and the knowledge gained from it, the endpoints

for the AVATAR study (ANAVEX®2-73-RS-002) were appropriately updated according to ICH guidelines and were approved by the U.K.

and Healthcare products Regulatory Agency (MHRA) and in Australia by the Human Research Ethics Committees (HREC), where the AVATAR study

was conducted.

Subsequently the AVATAR study was updated from a Phase 2 to a Phase 3 study.

The data of the AVATAR study was released in

February 2022.

The study met all primary and secondary efficacy and safety endpoints, with consistent improvements in primary

efficacy endpoint, RSBQ AUC (p = 0.037) response, and secondary efficacy endpoints, ADAMS (p = 0.010) and CGI-I (p = 0.037)

Efficacy endpoints demonstrated statistically significant and clinically meaningful reductions in Rett syndrome symptoms.

Convenient once daily oral liquid doses of up to 30mg of ANAVEX ® 2-73 were also well tolerated with good medication

All patients who participated in the study are eligible to receive ANAVEX ® 2-73 under a voluntary open

label extension protocol, which is currently ongoing.

In July 2020, we commenced the third study of ANAVEX ® 2-73

for the treatment of Rett syndrome, called the EXCELLENCE study.

This Phase 2/3 study in pediatric patients with Rett syndrome will evaluate

the safety and efficacy of ANAVEX ® 2-73 in approximately 84 pediatric patients, aged 5 to 18, over a 12-week treatment period

incorporating ANAVEX ® 2-73 specific precision medicine biomarkers.

All patients who participate in the study will be eligible

to receive ANAVEX ® 2-73 under a voluntary open label extension protocol.

Parkinson’s Disease

In September 2016, we presented positive preclinical

data for ANAVEX ® 2-73 in an animal model of Parkinson’s disease, which demonstrated significant improvements

on behavioral, histopathological, and neuroinflammatory endpoints.

data for ANAVEX ® 2-73 in an animal model of Parkinson’s disease, which demonstrated significant improvements on behavioral,

histopathological, and neuroinflammatory endpoints.

The study was funded by the Michael J.

Fox Foundation.

data announced in October 2017 indicates that ANAVEX ® 2-73 induces robust neurorestoration in experimental Parkinsonism.

The encouraging results we have gathered in this model, coupled with the favorable profile of this compound in the Alzheimer’s

disease trial, support the notion that ANAVEX ® 2-73 is a promising clinical candidate drug for Parkinson’s

disease dementia.

In October 2020, we completed a double-blind,

randomized, placebo-controlled proof-of-concept Phase 2 trial with ANAVEX ® 2-73 in Parkinson’s Disease Dementia

(PDD), to study the effect of the compound on both the cognitive and motor impairment of Parkinson’s disease.

study enrolled approximately 132 patients for 14 weeks, randomized 1:1:1 to two different ANAVEX ® 2-73 doses, 30mg

and 50mg, or placebo.

The ANAVEX ® 2-73 Phase 2 PDD study design incorporated genomic precision medicine biomarkers

identified in the ANAVEX ® 2-73 Phase 2a Alzheimer’s disease study.

Within this study ANAVEX ® 2-73

was safe and well tolerated in oral doses up to 50mg once daily.

The results show clinically meaningful, dose-dependent, and statistically

significant improvements in the Cognitive Drug Research (CDR) computerized assessment system analysis.

The study confirmed the

precision medicine approach of targeting SIGMAR1 as a genetic biomarker in response to ANAVEX ® 2-73.

In August 2020, we announced a financial commitment

by Shake It Up Australia Foundation for Parkinson’s Research to fund up to 50% of the costs of an Australian clinical study

to develop ANAVEX ® 2-73 for the disease modifying treatment of Parkinson’s disease.

The financial commitment

would be made through private placement purchases of our common stock at 200% of the fair market value on the purchase date and

will be contingent upon the completion of certain clinical trial milestones relating to the proposed clinical trial.

clinical trial will use a convenient, once-daily oral ANAVEX ® 2-73 formulation to confirm the potential disease modifying

features of ANAVEX ® 2-73 in an animal model of Parkinson’s disease.

Safety and efficacy will be investigated

in an appropriately powered placebo-controlled clinical study of Parkinson’s disease patients over at least 48-weeks including

ANAVEX ® 2-73-specific precision medicine biomarkers.

In January 2021, we announced we were awarded

a research grant of $1.0 million from The Michael J.

Fox Foundation

for Parkinson’s Research (MJFF) to develop ANAVEX ® 2-73 for the treatment of Parkinson’s

The award will explore utilization of PET imaging biomarkers to enable measurement of target engagement and pathway activation

of the sigma-1 receptor (SIGMAR1) with clinically relevant doses in people with Parkinson’s disease.

Additional data announced in

October 2017 indicates that ANAVEX ® 2-73 induces robust neurorestoration in experimental Parkinsonism.

The encouraging results

we have gathered in this model, coupled with the favorable profile of this compound in the Alzheimer’s disease trial, support the

notion that ANAVEX ® 2-73 is a promising clinical candidate drug for Parkinson’s disease dementia.

In October 2020, we completed a double-blind, randomized,

placebo-controlled proof-of-concept Phase 2 trial with ANAVEX ® 2-73 in Parkinson’s Disease Dementia (PDD), to study

the effect of the compound on both the cognitive and motor impairment of Parkinson’s disease.

The Phase 2 study enrolled approximately

132 patients for 14 weeks, randomized 1:1:1 to two different ANAVEX ® 2-73 doses, 30mg and 50mg, or placebo.

The ANAVEX ® 2-73

Phase 2 PDD study design incorporated genomic precision medicine biomarkers identified in the ANAVEX ® 2-73 Phase 2a Alzheimer’s

disease study.

Within this study ANAVEX ® 2-73 was safe

and well tolerated in oral doses up to 50mg once daily.

The results show clinically meaningful, dose-dependent, and statistically significant

improvements in the Cognitive Drug Research (CDR) computerized assessment system analysis.

Treatment with ANAVEX ® 2-73 also

resulted in clinically meaningful improvements as measured by the global composite score of Parkinson’s disease symptom severity,

MDS-UPDRS Total score on top of standard of care including dopaminergic therapy, levodopa and other anti-PD medications after 14 weeks

of treatment, suggesting ANAVEX ® 2-73’s potential global capability of slowing and reversing symptoms that progress

in Parkinson’s disease.

The study confirmed the precision medicine approach of targeting SIGMAR1 as a genetic biomarker in response

to ANAVEX ® 2-73.

In January 2021, we announced we were awarded a research

grant of $1.0 million from The Michael J.

Fox Foundation for Parkinson’s Research (MJFF) to develop ANAVEX ® 2-73

for the treatment of Parkinson’s disease.

The award will explore utilization of PET imaging biomarkers to enable measurement of

target engagement and pathway activation of the sigma-1 receptor (SIGMAR1) with clinically relevant doses in people with Parkinson’s

Frontotemporal Dementia

In July 2020, we commenced the First-in-Human

Phase 1 clinical trial of ANAVEX ® 3-71, which was previously granted orphan drug designation for the treatment of

Frontotemporal Dementia (FTD) by the FDA.

ANAVEX ® 3-71 is an orally administered small molecule targeting sigma-1

and M1 muscarinic receptors that is designed to be beneficial for neurodegenerative diseases.

In July 2020, we commenced the First-in-Human Phase

1 clinical trial of ANAVEX ® 3-71.

ANAVEX ® 3-71 was previously granted orphan drug designation for the treatment

of Frontotemporal Dementia (FTD) by the FDA.

ANAVEX ® 3-71 is an orally administered small molecule targeting sigma-1 and

M1 muscarinic receptors that is designed to be beneficial for neurodegenerative diseases.

In preclinical studies, ANAVEX ® 3-71

demonstrated disease-modifying activity against the major hallmarks of Alzheimer’s disease in transgenic (3xTg-AD) mice,

including cognitive deficits, amyloid and tau pathologies, as well as beneficial effects on mitochondrial dysfunction and neuroinflammation.

1 clinical trial will be a prospective double-blind, randomized, placebo-controlled study.

A total of at least 36 healthy male

and female subjects will be included.

Single escalating doses of ANAVEX ® 3-71 will be administered in order to evaluate

the safety, tolerability, and pharmacokinetics (PK) of ANAVEX ® 3-71 and the effects of food and gender on its PK

in healthy volunteers.

This study is expected to be followed by longer duration dosing including patients with FTD or other dementia

indications with unmet medical need, incorporating exploratory efficacy and disease biomarker measures .

Our research and development pipeline includes

ANAVEX ® 2-73 currently in three different clinical study indications, and several other compounds in different stages

of clinical and pre-clinical study.

Our proprietary SIGMACEPTOR™ Discovery

Platform produced small molecule drug candidates with unique modes of action, based on our understanding of sigma receptors.

receptors may be targets for therapeutics to combat many human diseases, both of neurodegenerative nature, including Alzheimer’s

disease, as well as of neurodevelopmental nature, like Rett syndrome.

When bound by the appropriate ligands, sigma receptors influence

the functioning of multiple biochemical signals that are involved in the pathogenesis (origin or development) of disease.

viruses including SARS-CoV-2 (COVID-19) induce cellular stress by intrinsic mitochondrial apoptosis and other related cellular

processes, in order to ensure survival and replication.

Hence, it is possible that S1R could play a role in modulating the cellular

response to viral infection and ameliorate pathogenesis.

demonstrated disease-modifying activity against the major hallmarks of Alzheimer’s disease in transgenic (3xTg-AD) mice, including

cognitive deficits, amyloid and tau pathologies, as well as beneficial effects on mitochondrial dysfunction and neuroinflammation.

clinical trial was a prospective double-blind, randomized, placebo-controlled study.

A total of 36 healthy male and female subjects were

Single escalating doses of ANAVEX ® 3-71 were administered in order to evaluate the safety, tolerability, and pharmacokinetics

(PK) of ANAVEX ® 3-71 and the effects of food and gender on its PK in healthy volunteers.

The study met

its primary and secondary endpoints of safety, with no serious adverse events (SAEs) or dose-limiting toxicities observed.

ANAVEX ® 3-71

was well tolerated in all cohorts receiving ANAVEX ® 3-71 in single doses ranging from 5 mg to 200 mg daily with no SAEs

and no significant lab abnormalities in any subject.

In the study, ANAVEX ® 3-71 exhibited linear pharmacokinetics.

Its pharmacokinetics

was also dose proportional for doses up to 160 mg.

Gender had no effect on the PK of the drug and food had no effect on the bioavailability

of ANAVEX ® 3-71.

The study also met the secondary objective of characterizing the effect of ANAVEX ® 3-71 on

electrocardiogram (ECG) parameters.

There were no clinically significant ECG parameters throughout the study.

Participant QTcF measures

were normal across all dose groups with no difference between ANAVEX®3-71 and placebo.

Based on these

results, and ANAVEX ® 3-71 pre-clinical profile, the Company intends to advance ANAVEX ® 3-71 into a biomarker-driven

clinical development dementia program for the treatment of FTD, schizophrenias and Alzheimer’s disease, evaluating longitudinal

effect of treatment with ANAVEX ® 3-71.

We believe the results of these studies could serve as the basis for advancing into

respective registration studies in the U.S.

Our research and development pipeline includes ANAVEX ® 2-73

currently in three different clinical study indications, and several other compounds in different stages of clinical and pre-clinical

Our proprietary SIGMACEPTOR™ Discovery Platform

produced small molecule drug candidates with unique modes of action, based on our understanding of sigma receptors.

Sigma receptors may

be targets for therapeutics to combat many human diseases, both of neurodegenerative nature, including Alzheimer’s disease, as well

as of neurodevelopmental nature, like Rett syndrome.

When bound by the appropriate ligands, sigma receptors influence the functioning

of multiple biochemical signals that are involved in the pathogenesis (origin or development) of disease.

Multiple viruses including SARS-CoV-2

(COVID-19) induce cellular stress by intrinsic mitochondrial apoptosis and other related cellular processes, in order to ensure survival

and replication.

Hence, it is possible that S1R could play a role in modulating the cellular response to viral infection and ameliorate

pathogenesis.

Compounds that have been subjects of our research

5 unchanged sentences

resulted in both significant and dose related improvements in an array of behavioral paradigms in the MECP2 HET Rett syndrome disease

In addition, in a further experiment sponsored by Rettsyndrome.org, ANAVEX ® 2-73 was evaluated in automatic

visual response and respiration tests in 7-month old mice, an age at which advanced pathology is evident.

Vehicle-treated MECP2

mice demonstrated fewer automatic visual responses than wild-type mice.

Treatment with ANAVEX ® 2-73 for four weeks

significantly increased the automatic visual response in the MECP2 Rett syndrome disease mouse.

Additionally, chronic oral dosing

daily for 6.5 weeks of ANAVEX ® 2-73 starting at ~5.5 weeks of age was conducted in the MECP2 HET Rett syndrome disease

mouse model assessed the different aspects of muscular coordination, balance, motor learning and muscular strengths, some of the

core deficits observed in Rett syndrome.

Administration of ANAVEX ® 2-73 resulted in both significant and dose related

improvements in an array of these behavioral paradigms in the MECP2 HET Rett syndrome disease model.

In March 2019, we commenced the first Phase

2 clinical trial in a planned Rett syndrome program of ANAVEX ® 2-73 for the treatment of Rett syndrome.

which took place in the United States, was completed in December 2020, however two other clinical trials in Rett syndrome, the

AVATAR study and the EXCELLENCE study, are still underway.

The studies are being conducted in a range of patient age demographics

and geographic regions, as more fully described above under Clinical Studies Overview – Rett Syndrome .

In May 2016 and June 2016, the FDA granted

Orphan Drug Designation to ANAVEX ® 2-73 for the treatment of Rett syndrome and infantile spasms, respectively.

November 2019, the FDA granted to ANAVEX ® 2-73 the Rare Pediatric Disease (RPD) designation for the treatment of

Rett syndrome.

The RPD designation provides priority review by the FDA to encourage the development of treatments for rare pediatric

Further, in February 2020, the FDA granted

Fast Track designation for the ANAVEX ® 2-73 clinical development program for the treatment of Rett syndrome.

FDA Fast Track program is designed to facilitate and expedite the development and review of new drugs to address unmet medical

needs in the treatment of serious and life-threatening conditions.

For Parkinson’s disease, data demonstrates

significant improvements and restoration of function in a disease modifying animal model of Parkinson’s disease.

improvements were seen on all measures tested:

In addition, in a further experiment sponsored by Rettsyndrome.org, ANAVEX ® 2-73 was evaluated in automatic visual

response and respiration tests in 7-month old mice, an age at which advanced pathology is evident.

Vehicle-treated MECP2 mice demonstrated

fewer automatic visual responses than wild-type mice.

Treatment with ANAVEX ® 2-73 for four weeks significantly increased

the automatic visual response in the MECP2 Rett syndrome disease mouse.

Additionally, chronic oral dosing daily for 6.5 weeks of ANAVEX ® 2-73

starting at ~5.5 weeks of age was conducted in the MECP2 HET Rett syndrome disease mouse model assessed the different aspects of muscular

coordination, balance, motor learning and muscular strengths, some of the core deficits observed in Rett syndrome.

Administration of ANAVEX ® 2-73

resulted in both significant and dose related improvements in an array of these behavioral paradigms in the MECP2 HET Rett syndrome disease

In May 2016 and June 2016, the FDA granted Orphan

Drug Designation to ANAVEX ® 2-73 for the treatment of Rett syndrome and infantile spasms, respectively.

In November 2019,

the FDA granted to ANAVEX ® 2-73 the Rare Pediatric Disease (RPD) designation for the treatment of Rett syndrome.

designation provides priority review by the FDA to encourage the development of treatments for rare pediatric diseases.

Further, in February 2020, the FDA granted Fast Track

designation for the ANAVEX ® 2-73 clinical development program for the treatment of Rett syndrome.

The FDA Fast Track program

is designed to facilitate and expedite the development and review of new drugs to address unmet medical needs in the treatment of serious

and life-threatening conditions.

For Parkinson’s disease, data demonstrates significant

improvements and restoration of function in a disease modifying animal model of Parkinson’s disease.

Significant improvements were

seen on all measures tested:

behavioral, histopathological, and neuroinflammatory endpoints.

In October 2020,

we completed a double-blind, randomized, placebo-controlled proof-of-concept Phase 2 trial with ANAVEX ® 2-73 in Parkinson’s

Disease Dementia (PDD), to study the effect of the compound on both the cognitive and motor impairment of Parkinson’s disease.

The Phase 2 study enrolled approximately 132 patients for 14 weeks, randomized 1:1:1 to two different ANAVEX ® 2-73

doses, 30mg and 50mg, or placebo.

The ANAVEX ® 2-73 Phase 2 PDD study design incorporated genomic precision medicine

biomarkers identified in the ANAVEX ® 2-73 Phase 2a Alzheimer’s disease study.

The study found that ANAVEX ® 2-73

was safe and well tolerated in oral doses up to 50mg once daily.

In October 2020, we completed a double-blind,

randomized, placebo-controlled proof-of-concept Phase 2 trial with ANAVEX ® 2-73 in Parkinson’s Disease Dementia (PDD),

to study the effect of the compound on both the cognitive and motor impairment of Parkinson’s disease.

The Phase 2 study enrolled

approximately 132 patients for 14 weeks, randomized 1:1:1 to two different ANAVEX ® 2-73 doses, 30mg and 50mg, or placebo.

The ANAVEX ® 2-73 Phase 2 PDD study design incorporated genomic precision medicine biomarkers identified in the ANAVEX ® 2-73

Phase 2a Alzheimer’s disease study.

The study found that ANAVEX ® 2-73 was

safe and well tolerated in oral doses up to 50mg once daily.

The results show clinically meaningful, dose-dependent, and statistically

significant improvements in the Cognitive Drug Research (CDR) computerized assessment system analysis.

We anticipate conducting

further clinical trials of ANAVEX ® 2-73 in Parkinson’s disease dementia after submitting the results of the

study to the FDA to obtain regulatory guidance.

In Alzheimer’s disease (AD) animal models,

ANAVEX ® 2-73 has shown pharmacological, histological and behavioral evidence as a potential neuroprotective, anti-amnesic,

anti-convulsive and anti-depressive therapeutic agent, due to its potent affinity to sigma-1 receptors and moderate affinities

to M1-4 type muscarinic receptors.

In addition, ANAVEX ® 2-73 has shown a potential dual mechanism which may impact

amyloid, tau pathology and inflammation.

In a transgenic AD animal model Tg2576, ANAVEX ® 2-73 induced a statistically

significant neuroprotective effect against the development of oxidative stress in the mouse brain, as well as significantly increased

the expression of functional and synaptic plasticity markers that is apparently amyloid-beta independent.

It also statistically

alleviated the learning and memory deficits developed over time in the animals, regardless of sex, both in terms of spatial working

memory and long-term spatial reference memory.

Based on the results of pre-clinical testing,

we initiated and completed a Phase 1 single ascending dose (SAD) clinical trial of ANAVEX ® 2-73.

In this Phase 1

SAD trial, the maximum tolerated single dose was defined per protocol as 55-60 mg.

This dose is above the equivalent dose shown

to have positive effects in mouse models of AD.

We anticipate conducting further

clinical trials of ANAVEX ® 2-73 in Parkinson’s disease dementia after submitting the results of the study to the FDA

to obtain regulatory guidance.

In Alzheimer’s disease (AD) animal models, ANAVEX ® 2-73

has shown pharmacological, histological and behavioral evidence as a potential neuroprotective, anti-amnesic, anti-convulsive and anti-depressive

therapeutic agent, due to its potent affinity to sigma-1 receptors and moderate affinities to M1-4 type muscarinic receptors.

ANAVEX ® 2-73 has shown a potential dual mechanism which may impact amyloid, tau pathology and inflammation.

In a transgenic

AD animal model Tg2576, ANAVEX ® 2-73 induced a statistically significant neuroprotective effect against the development

of oxidative stress in the mouse brain, as well as significantly increased the expression of functional and synaptic plasticity markers

that is apparently amyloid-beta independent.

It also statistically alleviated the learning and memory deficits developed over time in

the animals, regardless of sex, both in terms of spatial working memory and long-term spatial reference memory.

Based on the results of pre-clinical testing, we initiated

and completed a Phase 1 single ascending dose (SAD) clinical trial of ANAVEX ® 2-73.

In this Phase 1 SAD trial, the maximum

tolerated single dose was defined per protocol as 55-60 mg.

This dose is above the equivalent dose shown to have positive effects in mouse

models of AD.

There were no significant changes in laboratory or electrocardiogram (ECG) parameters.

ANAVEX ® 2-73 was well tolerated below the 55-60 mg dose with only mild adverse events in some subjects.

adverse events at doses above the maximum tolerated single dose included headache and dizziness, which were moderate in severity

and reversible.

These side effects are often seen with drugs that target CNS conditions, including AD.

In December 2014, a Phase 2a clinical trial

was initiated for ANAVEX ® 2-73, for the treatment of Alzheimer’s disease.

The open-label randomized trial was

designed to assess the safety and exploratory efficacy of ANAVEX ® 2-73 in 32 patients with mild-to-moderate Alzheimer’s

ANAVEX ® 2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1

and muscarinic receptors.

Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer’s.

The Phase 2a study met both primary and secondary objectives of the study.

ANAVEX ® 2-73 was well

tolerated below the 55-60 mg dose with only mild adverse events in some subjects.

Observed adverse events at doses above the maximum tolerated

single dose included headache and dizziness, which were moderate in severity and reversible.

These side effects are often seen with drugs

that target CNS conditions, including AD.

In December 2014, a Phase 2a clinical trial was initiated

for ANAVEX ® 2-73, for the treatment of Alzheimer’s disease.

The open-label randomized trial was designed to assess

the safety and exploratory efficacy of ANAVEX ® 2-73 in 32 patients with mild-to-moderate Alzheimer’s disease.

ANAVEX ® 2-73

is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors.

Preclinical studies

demonstrated its potential to halt and/or reverse the course of Alzheimer’s.

The Phase 2a study met both primary and secondary objectives

of the study.

In July 2018, we presented

the results of a genomic DNA and RNA evaluation of the participants in the Phase 2a study.

More than 33,000 genes were analyzed

using unbiased, data driven, machine learning, artificial intelligence (AI) system for analyzing DNA & RNA data in patients

exposed to ANAVEX ® 2-73.

The analysis identified genetic variants that impacted response to ANAVEX ® 2-73,

among them variants related to the Sigma-1 receptor (SIGMAR1), the target for ANAVEX ® 2-73.

Results showed that study

participants with the common SIGMAR1 wild type gene variant, which is about 80 percent of the population worldwide, demonstrated

improved cognitive (MMSE) and the functional (ADCS-ADL) scores.

The results from this evaluation have been used to establish a

precision medicine approach in subsequent clinical trials, since these signatures can now be applied to neurological indications

tested in clinical studies with ANAVEX ® 2-73 including Alzheimer’s disease, Parkinson’s disease dementia

and Rett syndrome.

More than 33,000 genes were analyzed using

unbiased, data driven, machine learning, artificial intelligence (AI) system for analyzing DNA & RNA data in patients exposed to ANAVEX ® 2-73.

The analysis identified genetic variants that impacted response to ANAVEX ® 2-73, among them variants related to the Sigma-1

receptor (SIGMAR1), the target for ANAVEX ® 2-73.

Results showed that study participants with the common SIGMAR1 wild type

gene variant, which is about 80 percent of the population worldwide, demonstrated improved cognitive (MMSE) and the functional (ADCS-ADL)

The results from this evaluation have been used to establish a precision medicine approach in subsequent clinical trials, since

these signatures can now be applied to neurological indications tested in clinical studies with ANAVEX ® 2-73 including Alzheimer’s

disease, Parkinson’s disease dementia and Rett syndrome.

ANAVEX ® 2-73

data presented met prerequisite information in order to progress into a Phase 2b/3 placebo-controlled study.

On July 2, 2018, the

Human Research Ethics Committee in Australia approved the initiation of our Phase 2b/3, double-blind, randomized, placebo-controlled

48-week safety and efficacy trial of ANAVEX ® 2-73 for the treatment of early Alzheimer’s disease.

trial sites in Canada, the United Kingdom, the Netherlands and Germany were also added.

This Phase 2b/3 study design incorporates

inclusion of genomic precision medicine biomarkers identified in the ANAVEX ® 2-73 Phase 2a study.

The Phase 2b/3

study, which has completed enrollment, randomized 1:1:1 to either two different ANAVEX ® 2-73 doses or placebo, commenced

in October 2018.

On July 2, 2018, the Human

Research Ethics Committee in Australia approved the initiation of our Phase 2b/3, double-blind, randomized, placebo-controlled 48-week

safety and efficacy trial of ANAVEX ® 2-73 for the treatment of early Alzheimer’s disease.

Clinical trial sites in

Canada, the United Kingdom, the Netherlands and Germany were also added.

This Phase 2b/3 study design incorporates inclusion of genomic

precision medicine biomarkers identified in the ANAVEX ® 2-73 Phase 2a study.

The Phase 2b/3 study, which commenced in October 2018, randomized 1:1:1 to either two different ANAVEX ® 2-73

doses or placebo, completed enrollment in June 2021.

Preclinical data also validates ANAVEX ® 2-73

as a prospective platform drug for other neurodegenerative diseases beyond Alzheimer’s disease, Parkinson’s disease

or Rett syndrome, more specifically, epilepsy, infantile spasms, Fragile X syndrome, Angelman syndrome, multiple sclerosis and,

more recently, tuberous sclerosis complex (TSC).

ANAVEX ® 2-73 demonstrated significant improvements in all of these

indications in the respective preclinical animal models.

In a study sponsored by the Foundation for

Angelman Syndrome, ANAVEX ® 2-73 was assessed in a mouse model for the development of audiogenic seizures.

indicated that ANAVEX ® 2-73 administration significantly reduced audiogenic-induced seizures.

In a study sponsored

by FRAXA Research Foundation regarding Fragile X syndrome, data demonstrated that ANAVEX ® 2-73 restored hippocampal

brain-derived neurotrophic factor (BDNF) expression to normal levels.

BDNF under-expression has been observed in many neurodevelopmental

and neurodegenerative pathologies.

as a prospective platform drug for other neurodegenerative diseases beyond Alzheimer’s disease, Parkinson’s disease or Rett

syndrome, more specifically, epilepsy, infantile spasms, Fragile X syndrome, Angelman syndrome, multiple sclerosis and, more recently,

tuberous sclerosis complex (TSC).

ANAVEX ® 2-73 demonstrated significant improvements in all of these indications in the

respective preclinical animal models.

In a study sponsored by the Foundation for Angelman

Syndrome, ANAVEX ® 2-73 was assessed in a mouse model for the development of audiogenic seizures.

The results indicated that

ANAVEX ® 2-73 administration significantly reduced audiogenic-induced seizures.

In a study sponsored by FRAXA Research Foundation

regarding Fragile X syndrome, data demonstrated that ANAVEX ® 2-73 restored hippocampal brain-derived neurotrophic factor

(BDNF) expression to normal levels.

BDNF under-expression has been observed in many neurodevelopmental and neurodegenerative pathologies.

BDNF signaling promotes maturation of both excitatory and inhibitory synapses.

ANAVEX ® 2-73

normalization of BDNF expression could be a contributing factor for the positive data observed in both neurodevelopmental and neurodegenerative

disorders like Angelman and Fragile X syndromes.

Preclinical data presented also indicates that

ANAVEX ® 2-73 demonstrates protective effects of mitochondrial enzyme complexes during pathological conditions, which,

if impaired, are believed to play a role in the pathogenesis of neurodegenerative and neurodevelopmental diseases.

Preclinical data on ANAVEX ® 2-73

related to multiple sclerosis indicates that ANAVEX ® 2-73 may promote remyelination in multiple sclerosis disease.

Further, data also demonstrates that ANAVEX ® 2-73 provides protection for oligodendrocytes (“OL’s”)

and oligodendrocyte precursor cells (“OPC’s”), as well as central nervous system neurons in addition to helping

repair by increasing OPC proliferation and maturation in tissue culture.

In March 2018, we presented preclinical data

of ANAVEX ® 2-73 in a genetic mouse model of tuberous sclerosis complex (“TSC”).

TSC is a rare genetic

disorder characterized by the growth of numerous benign tumors in many parts of the body with a high incidence of seizures.

new preclinical data demonstrates that treatment with ANAVEX ® 2-73 significantly increases survival and reduces seizures.

ANAVEX ® 2-73 normalization of BDNF expression

could be a contributing factor for the positive data observed in both neurodevelopmental and neurodegenerative disorders like Angelman

and Fragile X syndromes.

Preclinical data presented also indicates that ANAVEX ® 2-73

demonstrates protective effects of mitochondrial enzyme complexes during pathological conditions, which, if impaired, are believed to

play a role in the pathogenesis of neurodegenerative and neurodevelopmental diseases.

Preclinical data on ANAVEX ® 2-73 related

to multiple sclerosis indicates that ANAVEX ® 2-73 may promote remyelination in multiple sclerosis disease.

Further, data

also demonstrates that ANAVEX ® 2-73 provides protection for oligodendrocytes (“OL’s”) and oligodendrocyte

precursor cells (“OPC’s”), as well as central nervous system neurons in addition to helping repair by increasing OPC

proliferation and maturation in tissue culture.

In March 2018, we presented preclinical data of ANAVEX ® 2-73

in a genetic mouse model of tuberous sclerosis complex (“TSC”).

TSC is a rare genetic disorder characterized by the growth

of numerous benign tumors in many parts of the body with a high incidence of seizures.

The preclinical data demonstrates that treatment

with ANAVEX ® 2-73 significantly increases survival and reduces seizures.

ANAVEX ® 3-71

ANAVEX ® 3-71 is a clinical drug

candidate with a novel mechanism of action via sigma-1 receptor activation and M1 muscarinic allosteric modulation, which has been

shown to enhance neuroprotection and cognition in Alzheimer’s disease models.

ANAVEX ® 3-71 is a CNS-penetrable

potential disease modifying treatment for cognitive impairments.

It is highly effective in very small doses against the major Alzheimer’s

hallmarks in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid and tau pathologies, and also has beneficial effects

on inflammation and mitochondrial dysfunctions.

ANAVEX ® 3-71 indicates extensive therapeutic advantages in Alzheimer’s

and other protein-aggregation-related diseases given its ability to enhance neuroprotection and cognition via sigma-1 receptor

activation and M1 muscarinic allosteric modulation.

A preclinical study examined the response of

ANAVEX ® 3-71 in aged transgenic animal models and showed a significant reduction in the rate of cognitive deficit,

amyloid beta pathology and inflammation with the administration of ANAVEX 3-71.

In April 2016, the FDA granted Orphan Drug Designation

to ANAVEX ® 3-71 for the treatment of Frontotemporal dementia (FTD).

ANAVEX ® 3-71 is a clinical drug candidate

with a novel mechanism of action via sigma-1 receptor activation and M1 muscarinic allosteric modulation, which has been shown to enhance

neuroprotection and cognition in Alzheimer’s disease models.

ANAVEX ® 3-71 is a CNS-penetrable potential disease modifying

treatment for cognitive impairments.

It is highly effective in very small doses against the major Alzheimer’s hallmarks in transgenic

(3xTg-AD) mice, including cognitive deficits, amyloid and tau pathologies, and also has beneficial effects on inflammation and mitochondrial

dysfunctions.

ANAVEX ® 3-71 indicates extensive therapeutic advantages in Alzheimer’s and other protein-aggregation-related

diseases given its ability to enhance neuroprotection and cognition via sigma-1 receptor activation and M1 muscarinic allosteric modulation.

A preclinical study examined the response of ANAVEX ® 3-71

in aged transgenic animal models and showed a significant reduction in the rate of cognitive deficit, amyloid beta pathology and inflammation

with the administration of ANAVEX 3-71.

In April 2016, the FDA granted Orphan Drug Designation to ANAVEX ® 3-71 for the treatment

of Frontotemporal dementia (FTD).

During pathological conditions ANAVEX ® 3-71

demonstrated the formation of new synapses between neurons (synaptogenesis) without causing an abnormal increase in the number

of astrocytes.

In neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, synaptogenesis is believed

to be impaired.

Additional preclinical data presented also indicates that in addition to reducing oxidative stress, ANAVEX ® 3-71

demonstrates protective effects of mitochondrial enzyme complexes during pathological conditions, which, if impaired, are believed

to play a role in the pathogenesis of neurodegenerative and neurodevelopmental diseases.

In July 2020, we commenced the first Phase

1 clinical trial of ANAVEX ® 3-71, with focus on the treatment of Frontotemporal Dementia (FTD) and other

dementia indications with unmet medical need .

The study is more fully described above under Clinical Studies Overview

– Frontotemporal Dementia .

demonstrated the formation of new synapses between neurons (synaptogenesis) without causing an abnormal increase in the number of astrocytes.

In neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, synaptogenesis is believed to be impaired.

preclinical data presented also indicates that in addition to reducing oxidative stress, ANAVEX ® 3-71 demonstrates protective

effects of mitochondrial enzyme complexes during pathological conditions, which, if impaired, are believed to play a role in the pathogenesis

of neurodegenerative and neurodevelopmental diseases.

In July 2020, we commenced the first Phase 1 clinical

trial of ANAVEX ® 3-71.

The study took place in Australia and was a double-blind, randomized, placebo-controlled, Phase

1 trial to evaluate safety and tolerability, and pharmacokinetics (PK) of oral escalating doses of ANAVEX ® 3-71

including effects of food and gender in healthy volunteers The study met its primary and secondary

endpoints of safety, respectively with no serious adverse events (SAEs) or dose-limiting toxicities observed, as more fully described

above under Clinical Studies Overview – Frontotemporal Dementia .

Based on these

results, and ANAVEX ® 3-71 pre-clinical profile, the Company intends to advance ANAVEX ® 3-71 into a biomarker-driven

clinical development dementia program for the treatment of FTD, schizophrenias and Alzheimer’s disease, evaluating longitudinal

effect of treatment with ANAVEX ® 3-71.

Anavex believes the results of these studies, could serve as the basis for advancing

into respective registration studies in the U.S.

ANAVEX ® 1-41

ANAVEX ® 1-41 is a sigma-1 receptor

Pre-clinical tests revealed significant neuroprotective benefits (i.e., protects nerve cells from degeneration or death)

through the modulation of endoplasmic reticulum, mitochondrial and oxidative stress, which damages and impairs cell viability.

In addition, in animal models, ANAVEX ® 1-41 prevented the expression of caspase-3, an enzyme that plays a key role

in apoptosis (programmed cell death) and loss of cells in the hippocampus, the part of the brain that regulates learning, emotion

These activities involve both muscarinic and sigma-1 receptor systems through a novel mechanism of action.

Preclinical data presented also indicates that

ANAVEX ® 1-41 demonstrates protective effects of mitochondrial enzyme complexes during pathological conditions, which,

if impaired, are believed to play a role in the pathogenesis of neurodegenerative and neurodevelopmental diseases.

ANAVEX ® 1-41 is a sigma-1 agonist.

tests revealed significant neuroprotective benefits (i.e., protects nerve cells from degeneration or death) through the modulation of

endoplasmic reticulum, mitochondrial and oxidative stress, which damages and impairs cell viability.

In addition, in animal models, ANAVEX ® 1-41

prevented the expression of caspase-3, an enzyme that plays a key role in apoptosis (programmed cell death) and loss of cells in the hippocampus,

the part of the brain that regulates learning, emotion and memory.

These activities involve both muscarinic and sigma-1 receptor systems

through a novel mechanism of action.

Preclinical data presented also indicates that ANAVEX ® 1-41

demonstrates protective effects of mitochondrial enzyme complexes during pathological conditions, which, if impaired, are believed to

play a role in the pathogenesis of neurodegenerative and neurodevelopmental diseases.

ANAVEX ® 1066

3 unchanged sentences

models of neuropathic and visceral pain that have been extensively validated in rats.

In the chronic constriction injury model

of neuropathic pain, a single oral administration of ANAVEX ® 1066 dose-dependently restored the nociceptive threshold

in the affected paw to normal levels while leaving the contralateral healthy paw unchanged.

Efficacy was rapid and remained significant

for two hours.

In a model of visceral pain, chronic colonic hypersensitivity was induced by injection of an inflammatory agent

directly into the colon and a single oral administration of ANAVEX ® 1066 returned the nociceptive threshold to control

levels in a dose-dependent manner.

Companion studies in rats demonstrated the lack of any effects on normal gastrointestinal transit

with ANAVEX ® 1066 and a favorable safety profile in a battery of behavioral measures.

In the chronic constriction injury model of neuropathic

pain, a single oral administration of ANAVEX ® 1066 dose-dependently restored the nociceptive threshold in the affected paw

to normal levels while leaving the contralateral healthy paw unchanged.

Efficacy was rapid and remained significant for two hours.

a model of visceral pain, chronic colonic hypersensitivity was induced by injection of an inflammatory agent directly into the colon and

a single oral administration of ANAVEX ® 1066 returned the nociceptive threshold to control levels in a dose-dependent manner.

Companion studies in rats demonstrated the lack of any effects on normal gastrointestinal transit with ANAVEX ® 1066 and

a favorable safety profile in a battery of behavioral measures.

ANAVEX ® 1037

ANAVEX ® 1037 is designed for

the treatment of prostate and pancreatic cancer.

It is a low molecular weight, synthetic compound exhibiting high affinity for

sigma-1 receptors at nanomolar levels and moderate affinity for sigma-2 receptors and sodium channels at micromolar levels.

advanced pre-clinical studies, this compound revealed antitumor potential.

It has also been shown to selectively kill human cancer

cells without affecting normal/healthy cells and also to significantly suppress tumor growth in immune-deficient mice models.

publications highlight the possibility that these ligands may stop tumor growth and induce selective cell death in various tumor

Sigma receptors are highly expressed in different tumor cell types.

Binding by appropriate sigma-1 and/or sigma-2 ligands

can induce selective apoptosis.

In addition, through tumor cell membrane reorganization and interactions with ion channels, our

drug candidates may play an important role in inhibiting the processes of metastasis (spreading of cancer cells from the original

site to other parts of the body), angiogenesis (the formation of new blood vessels) and tumor cell proliferation.

Our compounds are in the clinical and pre-clinical

testing stages of development, and there is no guarantee that the activity demonstrated in pre-clinical models will be shown in

human testing.

We continue to identify and initiate discussions

with potential strategic and commercial partners to most effectively advance our programs and realize maximum shareholder value.

Further, we may acquire or develop new intellectual property and assign, license, or otherwise transfer our intellectual property

to further our goals.

ANAVEX ® 1037 is designed for the treatment

of prostate and pancreatic cancer.

It is a low molecular weight, synthetic compound exhibiting high affinity for sigma-1 receptors at

nanomolar levels and moderate affinity for sigma-2 receptors and sodium channels at micromolar levels.

In advanced pre-clinical studies,

this compound revealed antitumor potential.

It has also been shown to selectively kill human cancer cells without affecting normal/healthy

cells and also to significantly suppress tumor growth in immune-deficient mice models.

Scientific publications highlight the possibility

that these ligands may stop tumor growth and induce selective cell death in various tumor cell lines.

Sigma receptors are highly expressed

in different tumor cell types.

Binding by appropriate sigma-1 and/or sigma-2 ligands can induce selective apoptosis.

In addition, through

tumor cell membrane reorganization and interactions with ion channels, our drug candidates may play an important role in inhibiting the

processes of metastasis (spreading of cancer cells from the original site to other parts of the body), angiogenesis (the formation of

new blood vessels) and tumor cell proliferation.

Our compounds are in the pre-clinical and clinical

testing stages of development, and there is no guarantee that the activity demonstrated in pre-clinical models will be shown in human

We continue to identify and initiate discussions with

potential strategic and commercial partners to most effectively advance our programs and realize maximum shareholder value.

may acquire or develop new intellectual property and assign, license, or otherwise transfer our intellectual property to further our goals.

Our Target Indications

We have developed compounds with potential

application to two broad categories and several specific indications.

We have developed compounds with potential application

to two broad categories and several specific indications.

Central Nervous System Diseases

● Alzheimer’s

disease – In 2020, an estimated 5.8 million Americans were suffering from Alzheimer’s

The Alzheimer’s Association ® estimates that by 2050, this number

will rise to nearly 14 million Americans.

Medications on the market today treat only the

symptoms of Alzheimer’s disease and do not have the ability to stop its onset or its

There is an urgent and unmet need for both a disease modifying cure for Alzheimer’s

disease as well as for better symptomatic treatments.

● Parkinson’s

disease – Parkinson’s disease is a progressive disease of the nervous system

● Alzheimer’s disease – In 2021, an estimated 5.7 million Americans were suffering from Alzheimer’s

The Alzheimer’s Association ® estimates that by 2050, this number will rise to nearly 14 million Americans.

Medications on the market today treat only the symptoms of Alzheimer’s disease and do not have the ability to stop its onset or

its progression.

There is an urgent and unmet need for both a disease modifying cure for Alzheimer’s disease as well as for better

symptomatic treatments.

● Parkinson’s disease – Parkinson’s disease is a progressive disease of the nervous system

marked by tremors, muscular rigidity, and slow, imprecise movement.

It is associated with

degeneration of the basal ganglia of the brain and a deficiency of the neurotransmitter dopamine.

Parkinson’s disease afflicts more than 10 million people worldwide, typically middle-aged

and elderly people.

The Parkinson’s disease market is expected to expand to $11.5 billion

by 2029, according to business intelligence provider GBI Research.

syndrome – Rett syndrome is a rare X-linked genetic neurological and developmental

disorder that affects the way the brain develops, including protein transcription, which

is altered and as a result leads to severe disruptions in neuronal homeostasis.

It is considered

a rare, progressive neurodevelopmental disorder and is caused by a single mutation in the

Because males have a different chromosome combination from females, boys who

have the genetic MECP2 mutation are affected in devastating ways.

Most of them die before

birth or in early infancy.

For females who survive infancy, Rett syndrome leads to severe

impairments, affecting nearly every aspect of the child’s life;

severe mental retardation,

their ability to speak, walk and eat, sleeping problems, seizures and even the ability to

breathe easily.

It is associated with degeneration of the basal ganglia of the brain

and a deficiency of the neurotransmitter dopamine.

Parkinson’s disease afflicts more than 10 million people worldwide, typically

middle-aged and elderly people.

The Parkinson’s disease market is expected to expand to $11.5 billion by 2029, according to business

intelligence provider GBI Research.

● Rett syndrome – Rett syndrome is a rare X-linked genetic neurological and developmental disorder

that affects the way the brain develops, including protein transcription, which is altered and as a result lead to severe disruptions

in neuronal homeostasis.

It is considered a rare, progressive neurodevelopmental disorder and is caused by a single mutation in the MECP2

Because males have a different chromosome combination from females, boys who have the genetic MECP2 mutation are affected in devastating

Most of them die before birth or in early infancy.

For females who survive infancy, Rett syndrome leads to severe impairments, affecting

nearly every aspect of the child’s life;

severe mental retardation, their ability to speak, walk and eat, sleeping problems, seizures

and even the ability to breathe easily.

Rett syndrome affects approximately 1 in every 10,000-15,000 females.

– Depression is a major cause of morbidity worldwide according to the World Health

Organization.

Pharmaceutical treatment for depression is dominated by blockbuster brands,

with the leading nine brands historically accounting for approximately 75% of total sales.

However, the dominance of the leading brands is waning, largely due to the effects of patent

expiration and generic competition.

– Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked

These seizures are transient signs and/or symptoms of abnormal, excessive or synchronous

neuronal activity in the brain.

According to the Centers for Disease Control and Prevention,

in 2015 epilepsy affected 3.4 million Americans.

Today, epilepsy is often controlled, but

not cured, with medication that is categorized as older traditional anti-epileptic drugs

and second generation anti-epileptic drugs.

Because epilepsy afflicts sufferers in different

ways, there is a need for drugs used in combination with both traditional anti-epileptic

● Depression – Depression is a major cause of morbidity worldwide according to the World Health Organization.

Pharmaceutical treatment for depression is dominated by blockbuster brands, with the leading nine brands historically accounting for approximately

75% of total sales.

However, the dominance of the leading brands is waning, largely due to the effects of patent expiration and generic

● Epilepsy – Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked

These seizures are transient signs and/or symptoms of abnormal, excessive or synchronous neuronal activity in the brain.

to the Centers for Disease Control and Prevention, in 2015 epilepsy affected 3.4 million Americans.

Today, epilepsy is often controlled,

but not cured, with medication that is categorized as older traditional anti-epileptic drugs and second generation anti-epileptic drugs.

Because epilepsy afflicts sufferers in different ways, there is a need for drugs used in combination with both traditional anti-epileptic

drugs and second generation anti-epileptic drugs.

Neuropathic Pain –

We define neuralgia, or neuropathic pain, as pain that is not related to activation of pain receptor cells in any part of the body.

Neuralgia is more difficult to treat than some other types of pain because it does not respond well to normal pain medications.

medications have become more specific to neuralgia and typically fall under the category of membrane stabilizing drugs or antidepressants.

Melanoma – Predominantly a skin cancer, malignant melanoma can also occur in melanocytes

● Neuropathic Pain – We define neuralgia, or neuropathic pain, as pain that is not related to activation

of pain receptor cells in any part of the body.

Neuralgia is more difficult to treat than some other types of pain because it does not

respond well to normal pain medications.

Special medications have become more specific to neuralgia and typically fall under the category

of membrane stabilizing drugs or antidepressants.

● Malignant Melanoma – Predominantly a skin cancer, malignant melanoma can also occur in melanocytes

found in the bowel and the eye.

Malignant melanoma accounts for 75% of all deaths associated

with skin cancer.

The treatment includes surgical removal of the tumor, adjuvant treatment,

chemo and immunotherapy, or radiation therapy.

According to IMS Health the worldwide malignant

melanoma market is expected to grow to $4.4 billion by 2022.

Cancer – Specific to men, prostate cancer is a form of cancer that develops in the

prostate, a gland in the male reproductive system.

The cancer cells may metastasize from

the prostate to other parts of the body, particularly the bones and lymph nodes.

Drug therapeutics

for prostate cancer are expected to increase to nearly $13.5 billion in 2024 according to

Datamonitor Healthcare.

Cancer – Pancreatic cancer is a malignant neoplasm of the pancreas.

Malignant melanoma accounts for 75% of all deaths associated with skin cancer.

The treatment includes

surgical removal of the tumor, adjuvant treatment, chemo and immunotherapy, or radiation therapy.

According to iHealthcareAnalyst, Inc.

the worldwide malignant melanoma market is expected to grow to $6.4 billion by 2027.

● Prostate Cancer – Specific to men, prostate cancer is a form of cancer that develops in the prostate,

a gland in the male reproductive system.

The cancer cells may metastasize from the prostate to other parts of the body, particularly the

bones and lymph nodes.

Drug therapeutics for prostate cancer are expected to increase to nearly $13.5 billion in 2024 according to Datamonitor

● Pancreatic Cancer – Pancreatic cancer is a malignant neoplasm of the pancreas.

In the United States,

approximately 55,000 new cases of pancreatic cancer will be diagnosed this year and approximately

44,000 patients will die as a result of their cancer, according to the American Cancer Society.

Sales predictions by GBI Research forecast that the market for the pharmaceutical treatment

of pancreatic cancer in the United States and five largest European countries willincrease

to $2.9 billion by 2021.

Patents, Trademarks and Intellectual

We hold ownership or exclusive rights to thirteen

patents, seventeen U.S.

approximately 55,000 new cases of pancreatic cancer will be diagnosed this year and approximately 44,000 patients will die as a result

of their cancer, according to the American Cancer Society.

Sales predictions by FutureWise forecast that the market for the global pharmaceutical

treatment of pancreatic cancer will increase to $4.7 billion by 2027.

Patents, Trademarks and Intellectual Property

We hold ownership or exclusive rights to fifteen U.S.

patents, sixteen U.S.

patent applications, and various PCT or ex-U.S.

patent applications relating to our drug candidates,

methods associated therewith, and to our research programs.

patent applications relating to our drug candidates, methods associated

therewith, and to our research programs.

We own one issued U.S.

2 unchanged sentences

directed to a novel and synergistic neuroprotective compound combined with donepezil and other cholinesterase inhibitors.

patent is expected to expire in June 2034, absent any patent term extension for regulatory delays.

We own two issued U.S.

each with claims directed to crystalline forms of ANAVEX ® 2-73.

The first of these two patents claims crystalline

forms of ANAVEX ® 2-73, dosage forms and compositions containing crystalline ANAVEX ® 2-73, and methods

of treatment for Alzheimer’s disease using them.

This patent is expected to expire in July 2036, absent any patent term extension

is expected to expire in June 2034, absent any patent term extension for regulatory delays.

We own three issued U.S.

patents each with

claims directed to crystalline forms of ANAVEX ® 2-73.

The first of these three patents claims crystalline forms of ANAVEX ® 2-73,

dosage forms and compositions containing crystalline ANAVEX ® 2-73, and methods of treatment for Alzheimer’s disease

This patent is expected to expire in July 2036, absent any patent term extension for regulatory delays.

The second of these

three patents claims pharmaceutical compositions containing a crystalline form of ANAVEX ® 2-73, and methods of treatment

for Alzheimer’s disease using the compositions.

This patent is expected to expire in June 2037, absent any patent term extension

for regulatory delays.

The second of these two patents claims pharmaceutical compositions containing a crystalline form of ANAVEX ® 2-73,

The third of these three patents claims pharmaceutical compositions containing a crystalline form of ANAVEX ® 2-73,

and methods of treatment for Alzheimer’s disease using the compositions.

This patent is expected to expire in June 2037,

absent any patent term extension for regulatory delays.

This patent is expected to expire in June 2037, absent

any patent term extension for regulatory delays.

We also own two issued U.S.

patents on seizure treatment.

these two patents claims methods and dosage forms for treating seizures, the dosage forms containing a low-dose anti-epilepsy drug

combined with either:

patents for seizure treatment.

The first of these two patents

claims methods and dosage forms for treating seizures, the dosage forms containing a low-dose anti-epilepsy drug combined with either:

(i) ANAVEX ® 2-73 and its active metabolite ANAVEX ® 19-144;

or (ii) ANAVEX ® 19-144.

The second of these two patents further claims the seizure treatment being co-timely or coordinated administration of anti-epilepsy

drugs and (i) ANAVEX ® 19-144 or (ii) ANAVEX 19-144 ® with ANAVEX 2-73 ® .

are expected to expire in October 2035, absent any patent term extension for regulatory delays.

We also own two issued U.S.

with claims directed to treating neurodevelopmental disorders.

These patents claim methods for treating a neurodevelopmental disorder

or multiple sclerosis by administering ANAVEX ® 2-73, ANAVEX ® 19-144, and/or ANAVEX ® 1-41

(another sigma receptor ligand similar to ANAVEX ® 2-73), or compositions thereof.

of these two patents further claims a combination seizure treatment involving administration of an anti-epilepsy drug combined with (i)

ANAVEX ® 19-144, or (ii) ANAVEX 19-144 ® and ANAVEX 2-73 ® .

Both patents are expected to expire

in January 2037, absent any patent term extension for regulatory delays.

in October 2035, absent any patent term extension for regulatory delays.

We also own two issued U.S.

patents with claims directed to treating

neurodevelopmental disorders.

These patents claim methods for treating a neurodevelopmental disorder or multiple sclerosis by administering

ANAVEX ® 2-73, ANAVEX ® 19-144, and/or ANAVEX ® 1-41 (another sigma receptor ligand similar to

ANAVEX ® 2-73), or compositions thereof.

Both patents are expected to expire in January 2037, absent any patent term extension

for regulatory delays.

In addition, we own one issued U.S.

Patent with claims

directed to methods of treating melanoma with a compound related to ANAVEX ® 2-73.

This patent is expected to expire

in February 2030, absent any patent term extension for regulatory delays.

Patent with claims directed to methods of treating melanoma with a compound

related to ANAVEX ® 2-73.

This patent is expected to expire in February 2030, absent any patent term extension for regulatory

We also own an issued U.S.

patent that claims crystalline

forms of ANAVEX ® 19-144, dosage forms and compositions containing the crystalline forms of ANAVEX ® 19-144,

and methods of treatment for Alzheimer’s disease.

This patent is expected to expire in July 2036, absent any patent term

extension for regulatory delays.

patent that claims crystalline forms of ANAVEX ® 19-144, dosage forms and compositions

containing the crystalline forms of ANAVEX ® 19-144, and methods of treatment for Alzheimer’s disease.

is expected to expire in July 2036, absent any patent term extension for regulatory delays.

Further, we own one issued U.S.

claims directed to methods of treating cardiac dysfunction with ANAVEX ® 2-73 .

This patent is expected to expire in July

2038, absent any patent term extension for regulatory delays.

We also own two issued U.S.

patents related

to ANAVEX ® 1066.

The first of these two patents claims methods for treating or preventing pain using (+) ANAVEX ® 1066

The second patent claims methods for treating or preventing pain using (-) ANAVEX ® 1066 isomer Both patents

are expected to expire in November 2036, absent any patent term extension for regulatory delays.

patents related to ANAVEX ® 1066.

The first of these two patents claims methods for treating or preventing pain using (+) ANAVEX ® 1066 isomer.

patent claims methods for treating or preventing pain using (-) ANAVEX ® 1066 isomer.

Both patents are expected to expire

in November 2036, absent any patent term extension for regulatory delays.

For ANAVEX ® 2-73, ANAVEX ® 19-144,

ANAVEX ® 1-41, and ANAVEX ® 1066, we also have granted or pending applications in Australia, Canada,

China, Europe, Japan, and Hong Kong, and are expected to expire after 2035.

With regard to ANAVEX ® 3-71,

we own exclusive rights to two issued U.S.

patents with claims respectively directed to the ANAVEX ® 3-71 compound

and methods of treating various diseases including Alzheimer’s with the same.

These patents are expected to expire in April

2030, and January 2030, respectively, absent any patent term extension for regulatory delays.

We also own exclusive rights to related

patents or applications that are granted or pending in Australia, Canada, China, Europe, Japan, Korea, New Zealand, Russia, and

South Africa, and are expected to expire in January 2030.

We also own other patent applications directed

to enantiomers, crystals, formulations, uses, and patient selection methods that may provide additional protection for one or more

of our product candidates.

ANAVEX ® 1-41, and ANAVEX ® 1066, we also have granted or pending applications in Australia, Canada, China,

Europe, Japan, and Hong Kong, which are expected to expire after 2035.

With regard to ANAVEX ® 3-71, we own

exclusive rights to two issued U.S.

patents with claims respectively directed to the ANAVEX ® 3-71 compound and methods of

treating various diseases including Alzheimer’s with the same.

These patents are expected to expire in April 2030, and January 2030,

respectively, absent any patent term extension for regulatory delays.

We also own exclusive rights to related patents or applications

that are granted or pending in Australia, Canada, China, Europe, Japan, Korea, New Zealand, Russia, and South Africa, which are expected

to expire in January 2030.

We also own other patent applications directed to

enantiomers, crystals, formulations, uses, and patient selection methods that may provide additional protection for one or more of our

product candidates.

We regard patents and other intellectual property

2 unchanged sentences

including the selective development, protection, and exploitation of our intellectual property rights.

In addition to filings made

with intellectual property authorities, we protect our intellectual property and confidential information by means of carefully

considered processes of communication and the sharing of information, and by the use of confidentiality and non-disclosure agreements

and provisions for the same in contractor’s agreements.

While no agreement offers absolute protection, such agreements provide

some form of recourse in the event of disclosure, or anticipated disclosure.

Our intellectual property position, like that

of many biomedical companies, is uncertain and involves complex legal and technical questions for which important legal principles

are unresolved.

For more information regarding challenges to our existing or future patents, see “Risk Factors” “

in Part I, Item 1A of our Annual Report on Form 10-K filed with the Securities and Exchange Commission on December 28, 2020.

In addition to filings made with

intellectual property authorities, we protect our intellectual property and confidential information by means of carefully considered

processes of communication and the sharing of information, and by the use of confidentiality and non-disclosure agreements and provisions

for the same in contractor’s agreements.

While no agreement offers absolute protection, such agreements provide some form of recourse

in the event of disclosure, or anticipated disclosure.

intellectual property position, like that of many biomedical companies, is uncertain and involves complex legal and technical questions

for which important legal principles are unresolved.

For more information regarding challenges to our existing or future patents, see

“Risk Factors” “ in Part I, Item 1A of our Annual Report on Form 10-K filed with the Securities and Exchange Commission

on November 24, 2021.

Financial Highlights

At June 30, 2021, our cash position had increased

to $157.6 million, from $29.2 million at our fiscal year end of September 30, 2020.

Operating expenses for the third quarter of

fiscal 2021 were $11.4 million, compared to $8.1 million for the comparable quarter in fiscal 2020.

The operating expenses include an

aggregate of $2.3 million, as compared to $1.3 million in the third quarter of fiscal 2020, in non-cash charges related to the issuance

and vesting of stock options.

Our research and development expenses for the third quarter of fiscal 2021 were $9.0 million, compared

to $6.7 million in the comparable period in fiscal 2020.

The increase is attributable to the continued advancement of our ongoing clinical

Net loss for the third quarter of fiscal 2021

was $10.2 million, or $0.14 per share, as compared to $6.5 million, or $0.11 per share in the comparative quarter of fiscal 2020.

Results of Operations

are in the development stage and have not earned any revenues since our inception and we do not anticipate earning any revenues

until we can establish an alliance with other companies to develop, co-develop, license, acquire or market our products.

and nine months ended June 30, 2021 compared to three and nine months ended June 30, 2020.

the development stage and have not earned any revenues since our inception in 2004.

We do not anticipate earning any revenues until we

can establish an alliance with other companies to develop, co-develop, license, acquire or market our products.

Our operating costs consist primarily of research

and development activities including the cost of clinical studies and clinical supplies as well as clinical drug manufacturing and formulation.

Research and development expenses also include personnel related costs such as salaries and wages, and third-party contract research

organization (CRO) expenses in support of these clinical studies.

Personnel costs include salaries and wages, benefits, and non-cash

stock-based compensation charges associated with options and other equity awards granted to employees and consultants who are directly

engaged in support of our research and development activities.

General and administrative expenses consist

of personnel costs, expenses for outside professional services and expenses associated with operating as a public company.

Personnel costs

consist of salaries and wages, benefits and stock-based compensation for general and administrative personnel.

Outside professional services

and public company expenses include expenses related to compliance and reporting, additional insurance expenses, audit and SOX compliance,

expenses associated with patent research, applications and filings, investor and shareholder relations activities and other administrative

expenses and professional services.

ended December 31, 2021 compared to three months ended December 31, 2020

During the three months ended December 31, 2021, we

completed our second randomized placebo-controlled clinical trial of ANAVEX ® 2-73

for the treatment of Rett syndrome , the AVATAR Phase 3 study, and reported positive top-line results from this study in February

2022, as described above under Clinical Studies Overview – Rett Syndrome .

We continued to advance enrollment of our EXCELLENCE

international Phase 2/3 pediatric Rett syndrome clinical trial through the activation of additional clinical sites in new regions across

We also completed the first in human Phase 1 clinical trial of ANAVEX ® 3-71 with focus on the treatment of Frontotemporal

Dementia (FTD) and positive topline results were announced in January 2022, as described above under Clinical Studies Overview –

Frontotemporal Dementia.

Operating Expenses

Total operating

expenses for the third quarter of fiscal 2021 were $11.4 million, compared to $8.1 million for the comparable quarter of fiscal

Total operating expenses for the nine-month period ended June 30, 2021 were $29.8 million

compared to $23.6 million for the same period in fiscal 2020.

This represents an increase of $3.3 million for the three-month period

and $6.2 million for the nine-month period.

Research and development

expenses for the third quarter of fiscal 2021 were $9.0 million, compared to $6.7 million for the third quarter of fiscal 2020

and $23.6 million for the nine-month period ended June 30, 2021, as compared to $19.1 million for the applicable prior year period.

This increase in both the current quarter and the year-to-date period is attributable to the continued advancement of our ongoing

clinical trials, most notably, the expansion of our Phase 2b/3 Alzheimer’s disease trial internationally, and the

continued enrollment and advancement of the international Rett syndrome program.

General and administrative expenses increased

to $2.4 million for the three months ended June 30, 2021, as compared to $1.4 million for the third quarter of fiscal 2020.

general and administrative expenses increased to $6.1 million for the nine-month period ended June 30, 2021, as compared to $4.5

million for the applicable prior year period.

The increase in general and administrative expenses was primarily related to an increase

in our staff, corporate activities and transactions, and an increase in non-cash stock option compensation charges.

The net amount of other income was $1.3 million

for the three-month period ended June 30, 2021 as compared to $1.6 million for the three-month period ended June 30, 2020 and $3.7

million for the nine-month period as compared to $3.3 million for the comparable nine-month period in fiscal 2020.

experienced an increase in Australian research and development incentive income for the nine-month period, in connection with the

increase in eligible clinical activities in Australia over the comparable year to date period, however in the current quarter the

Company incurred foreign exchange losses which were related to the fluctuations in the Australian dollar against the US dollar

and its related impact on incentive and tax receivables.

Total operating expenses for the first quarter of

fiscal 2022 were $11.7 million, compared to $9.4 million for the comparable first quarter of fiscal 2021.

General and administrative expenses were $3.1 million

for the three months ended December 31, 2021, as compared to $1.5 million for the first quarter of fiscal 2021.

The increase is primarily

related to an increase in non-cash stock option compensation charges of $1.3 million period over period in connection with the vesting

of milestone-based options.

Our research and development expenses for the first

quarter of fiscal 2022 were $8.7 million, as compared to $7.9 million for the first quarter of fiscal 2021.

The increase is primarily

related to an increase in non-cash stock option compensation charges of $1.7 million period over period in connection with the vesting

of milestone-based options.

continue to see an increase in our research and development expenditures as we advance our ANAVEX ® 2-73 clinical studies,

including extension studies to allow us to continue to gather longer term data, continuing to advance our other pipeline compounds such

as ANAVEX ® 3-71, and as we continue to add additional staff to manage and support these clinical studies.

Other income (net)

The net amount of other income for the first quarter

of fiscal 2022 was $0.9 million as compared to $1.6 million for the comparable first quarter of fiscal 2021.

decrease in other income is attributable to a decrease in Australian research and development incentive income in connection with the

decrease in eligible clinical activities in Australia over the comparable period such as the completion of the ANAVEX ® 3-71

Phase 1 clinical study.

Foreign exchange

gains during the period are primarily related to the fluctuations in the Australian dollar against the US dollar and its related impact

on incentive and tax receivables during the period.

Net loss for the first quarter of fiscal 2022

was $10.9 million, or $0.14 per share, as compared to $7.9 million, or $0.12 per share in the comparative first quarter of fiscal 2021.

Liquidity and Capital Resources

Working Capital

June 30, 2021

December 31, 2021

September 30, 2021

1 unchanged sentence

$ 156,896,368

$ 161,616,490

Current Liabilities

1 unchanged sentence

$ 146,367,706

At June 30, 2021, we had $157.6 million in cash and cash equivalents, an increase of $128.3 million from September 30, 2020.

the nine-month period ended June 30, 2021, we received cash of $151.0 million, net of issuance costs, primarily from the issuance

of shares of common stock under the 2019 Purchase Agreement, through the Sales Agreement, as well as a registered direct offering,

each as more fully described elsewhere in this Quarterly Report.

Nine months ended June 30,

$ 150,818,104

At December 31, 2021, we held $151.1 million in cash and cash equivalents, a decrease of $1.0 million from September 30, 2021.

Cash expenditures

for the quarter of approximately $7.0 million were offset by a net reduction of incentive and tax receivables of $3.8 million, resulting

in a net cash used in operating activities of $3.5 million for the quarter.

We received cash from financing activities of $2.5 million

primarily from the issuance of shares of common stock under the Sales Agreement (as defined below).

We intend to continue to use our

capital resources to advance our clinical trials for ANAVEX ® 2-73 and ANAVEX ® 3-71, and to perform work necessary

to prepare for future development of our pipeline compounds.

Three months ended December 31,

Net cash flows used in operating activities

2 unchanged sentences

Net cash flows from financing activities

Increase in cash and cash equivalents

$ 128,311,027

(Decrease) increase in cash and cash equivalents

Cash flow used in operating activities

Net cash used in operating activities for the

first nine months of fiscal 2021 was $22.7 million, compared to $15.0 million during the comparable

period of fiscal 2020.

The principal reason for this increase in net cash used from operating activities in the current period is due

to an increase in research and development expenses and an increase in research and development incentive income receivable, as compared

to the comparable period.

first quarter of fiscal 2022 was $3.5 million, compared to $7.9 million during the comparable period of fiscal 2021.

The principal reason

for this decrease in net cash used in operating activities in the current period is due to the receipt of research and development incentive

tax refunds during the period, as compared to no such receipts during the comparable period.

Cash flow provided by financing activities

Cash provided by financing activities for the

first nine months in fiscal 2021 was $151.0 million, net of financing costs, primarily attributable

to cash received from the issuance of common shares at various market prices under the 2019 Purchase Agreement, the Sales Agreement and

a direct registered offering we completed for net proceeds of $46.9 million, after deducting expenses associated with the offering.

Cash provided by financing activities for the

first nine months in fiscal 2020 was $20.5 million, attributable to cash received from the issuance

of common shares at various market prices under the 2019 Purchase Agreement .

three months ended December 31, 2021 was $2.5 million, primarily attributable to cash received from the issuance of common shares at various

market prices under the Sales Agreement.

Cash provided

by financing activities for the three months ended December 31, 2020 was $26.0 million, attributable to cash received from the issuance

of common shares at various market prices under the 2019 Purchase Agreement and the Sales Agreement.

Other Financing

Purchase Agreement

On June 7, 2019, we

entered into a Purchase Agreement (the “2019 Purchase Agreement”) with Lincoln Park Capital Fund, LLC (“Lincoln

Park”), as amended on July 1, 2020, pursuant to which Lincoln Park committed to purchase up to $50.0 million of our common

Concurrently with the execution of the 2019 Purchase Agreement in 2019, we issued 324,383 shares of our common stock to

Lincoln Park as a fee for its commitment to purchase shares of our common stock under the 2019 Purchase Agreement and became obligated

to issue up to 162,191 shares pro rata, when and if Lincoln Park purchased, at our discretion, the $50.0 million aggregate commitment.

During the nine months ended June 30, 2021,

the Company issued to Lincoln Park an aggregate of 4,086,209 shares of common stock under the 2019 Purchase Agreement, including

4,007,996 shares of common stock for an aggregate purchase price of $24.1 million and 78,213 commitment shares.

June 30, 2021, no shares of our common stock remain available for purchase by Lincoln Park under the 2019 Purchase Agreement.

Controlled Equity Offering Sales Agreement

1, 2020, we entered into an Amended and Restated Sales Agreement (the “Sales Agreement”) with Cantor Fitzgerald

and SVB Leerink LLC (the “Sales Agents”), pursuant to which we may offer and sell shares of common stock

registered under an effective registration statement from time to time through the Sales Agents (the “At-the-Market Offering”).

Upon delivery of a placement notice based on

our instructions and subject to the terms and conditions of the Sales Agreement, the Sales Agents may sell shares of common stock

by methods deemed to be an “at the market offering”, in negotiated transactions at market prices prevailing at the

time of sale or at prices related to such prevailing market prices, or by any other method permitted by law, including negotiated

transactions, subject to our prior written consent.

Controlled Equity Offering

Sales Agreement

On May 1, 2020, we entered into an Amended and Restated

Sales Agreement (the “Sales Agreement”) with Cantor Fitzgerald & Co.

and SVB Leerink LLC (the “Sales Agents”),

pursuant to which we may offer and sell shares of common stock registered under an effective registration statement from time to time

through the Sales Agents (the “At-the-Market Offering”).

Upon delivery of a placement notice based on our instructions

and subject to the terms and conditions of the Sales Agreement, the Sales Agents may sell shares of common stock by methods deemed to

be an “at the market offering”, in negotiated transactions at market prices prevailing at the time of sale or at prices related

to such prevailing market prices, or by any other method permitted by law, including negotiated transactions, subject to our prior written

We are not obligated to make any sales of shares under the Sales Agreement.

We or the Sales Agents may suspend or terminate the At-the-Market Offering upon notice to the other party, subject to certain conditions.

The Sales Agents will act as agents on a commercially reasonable efforts basis consistent with their normal trading and sales practices

and applicable state and federal law, rules and regulations and the rules of Nasdaq.

We or the Sales Agents may suspend or terminate the

At-the-Market Offering upon notice to the other party, subject to certain conditions.

The Sales Agents will act as agents on a commercially

reasonable efforts basis consistent with their normal trading and sales practices and applicable state and federal law, rules and regulations

and the rules of Nasdaq.

We have agreed to pay the Sales Agents commissions

for their services of 3.0% of the gross proceeds from the sale of the shares pursuant to the Sales Agreement.

We have also agreed

to provide the Sales Agents with customary indemnification and contribution rights.

During the nine months ended June 30, 2021,

5,634,576 shares were sold pursuant to the At-the-Market Offering for gross proceeds of $79.1 million (net proceeds of $76.7 million

after deducting commissions and offering expenses).

Registered Direct Offering

On June 24, 2021, the Company completed a registered

direct offering off of the Company’s shelf registration statement on Form S-3 filed with the SEC on July 3, 2019.

issued 2,380,953 common shares at $21.00 per share for gross proceeds of $50.0 million (net proceeds of $46.9 million after deducting

offering fees and expenses).

Sheet Arrangements

have no off-balance sheet arrangements that have or are reasonably likely to have a current or future effect on our financial condition,

changes in financial condition, revenues or expenses, results of operations, liquidity, capital expenditures or capital resources

that are material to our stockholders.

We have also agreed to provide

the Sales Agents with customary indemnification and contribution rights.

During the three months ended

December 31, 2021, 99,588 shares were sold pursuant to the At-the-Market Offering for gross proceeds of $2.3 million (net proceeds of

$2.2 million after deducting commissions and offering expenses).

Off-Balance Sheet Arrangements

We have no off-balance sheet

arrangements that have or are reasonably likely to have a current or future effect on our financial condition, changes in financial condition,

revenues or expenses, results of operations, liquidity, capital expenditures or capital resources that are material to our stockholders.

CRITICAL ACCOUNTING POLICIES

We prepare our interim condensed

consolidated financial statements in accordance with accounting principles generally accepted in the United States of America,

and make estimates and assumptions that affect our reported amounts of assets, liabilities, revenue and expenses, and the related

disclosures of contingent liabilities.

We base our estimates on historical experience and other assumptions that we believe are

reasonable in the circumstances.

consolidated financial statements in accordance with accounting principles generally accepted in the United States of America, and make

estimates and assumptions that affect our reported amounts of assets, liabilities, revenue and expenses, and the related disclosures of

contingent liabilities.

We base our estimates on historical experience and other assumptions that we believe are reasonable in the circumstances.

Actual results may differ from these estimates.

1 unchanged sentence

changes in the critical accounting policies and estimates described in our Annual Report on Form 10-K for the year ended September 30,

30, 2020 as filed with the SEC on December 28, 2020.

2021 as filed with the SEC on November 24, 2021.

RECENT ACCOUNTING PRONOUNCEMENTS

1 unchanged sentence

Accounting Pronouncements” in notes to our Interim Condensed Consolidated Financial Statements included in this Form 10-Q.

and Qualitative Disclosures about Market Risks.

QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISKS.

Not applicable

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-Q

Item 2. Management’s Discussion and Analysis