What changed in this filing

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Item 2. Management’s Discussion and Analysis

2024-08-06 compared with 2024-05-09 · 328 added, 252 removed, 796 unchanged (42% of the section changed)

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without limitation, statements regarding:

volatility in our stock price and in the markets in general;

our ability to successfully conduct preclinical studies and clinical 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;

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 candidates’ ability to demonstrate efficacy or an acceptable safety profile;

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 studies and clinical trials;

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 trials;

the anticipated designs of our future clinical trials;

our ability to attract and retain qualified employees;

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 position and ability to obtain funding for our operations.

volatility in our stock

price and in the markets in general;

our ability to successfully

conduct preclinical studies and clinical 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;

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 candidates’

ability to demonstrate efficacy or an acceptable safety profile;

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 studies and clinical trials;

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 trials;

the anticipated designs

of our future clinical trials;

our ability to attract

and retain qualified employees;

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 position and ability to obtain funding for our operations.

We have based these forward-looking statements largely

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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.

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

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

the SIGMAR1, 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 (blarcamesine) target engagement or receptor occupancy with SIGMAR1

the SIGMAR1, 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 (blarcamesine) target engagement or receptor occupancy with SIGMAR1

in the brain.

S et al., Sci Rep.

Reyes S et al.,

Cellular Homeostasis

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A significant impact of the genomic biomarkers SIGMAR1, the direct target of ANAVEX ® 2-73 (blarcamesine)

a gene involved in memory function, on the drug response level was identified, leading to an early 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

(blarcamesine) specific biomarker hypothesis.

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of Health – Therapeutic Goods Administration’s compassionate use Special Access Scheme.

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

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

The Phase 2b/3 trial enrolled 509 patients,

which were treated with a convenient once-daily oral formulation of ANAVEX ® 2-73 for 48 weeks, randomized 1:1:1 to two different

ANAVEX ® 2-73 doses or placebo.

A larger Phase 2b/3 double-blind, placebo-controlled trial of ANAVEX ® 2-73

in Alzheimer’s disease commenced in August 2018.

The Phase 2b/3 trial enrolled 509 patients, which were treated with a convenient

once-daily oral formulation of ANAVEX ® 2-73 for 48 weeks, randomized 1:1:1 to two different ANAVEX ® 2-73

doses or placebo.

The trial took place at 52 sites across North America, Europe and Australia.

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

Scale – Cognitive Subscale test (“ADAS-Cog”), Alzheimer’s Disease Cooperative Study – Activities of Daily

Living (“ADCS-ADL”) and Clinical Dementia Rating – Sum of Boxes for cognition and function (“CDR-SB”).

addition to the primary endpoints, the ANAVEX ® 2-73 Phase 2b/3 trial design incorporated pre-specified statistical analyses

related to potential genomic precision medicine biomarkers previously identified in the ANAVEX ® 2-73 Phase 2a clinical trial.

The trial was completed in mid-2022 and, in December 2022, the Company presented positive topline results from the Phase 2b/3 clinical

ANAVEX ® 2-73 met the co-primary endpoints

ADAS-Cog and ADCS-ADL and key secondary endpoint CDR-SB.

ANAVEX ® 2-73 treatment slowed decline of cognition and function

in patients with early Alzheimer’s disease over 48 weeks.

In addition, patients treated with ANAVEX ® 2-73 had 1.84

times higher odds, or likelihood, to improve cognitively compared to placebo, with an ADAS-Cog score threshold change of -0.5 points or

better [Odds Ratio = 1.84 (p = 0.015)].

At clinically significant levels of improvement in function (ADCS-ADL score threshold change of

+3.5 points or better), patients treated with ANAVEX ® 2-73 had 2.67 times higher odds, or likelihood, to improve function

compared to placebo [Odds Ratio = 2.67 (p = 0.0255)].

Additionally, treatment with ANAVEX ® 2-73 reduced cognitive decline

at end of treatment, measured with the ADAS-Cog, as compared to placebo, by 45%, representing a treatment difference in mean score change

of -1.85 points (p=0.033).

Compared to placebo, ANAVEX ® 2-73 reduced clinical decline of cognition and function by 27% with

mean score difference of -0.42 points (p=0.040) as measured by the CDR-SB.

ANAVEX ® 2-73 was generally safe and well tolerated.

All statistical analyses were performed by outside consultancy companies.

In September 2023, we provided additional data demonstrating

that the clinical effect was complemented by two independent biomarkers.

A significant reduction in pathological amyloid beta levels in

plasma, as well as a significant slowing in the rate of pathological brain atrophy on Magnetic Resonance Imaging (MRI) scans.

biomarkers of amyloid beta pathology, plasma Aβ42/40 ratio increased significantly (P = 0.048), demonstrating strong anti-amyloid

effects of ANAVEX ® 2-73 in Alzheimer’s disease patients, while MRI revealed significant reduction in brain volume

loss, including whole brain (P = 0.0005), comparing treatment to placebo.

Furthermore, all pre-specified clinical endpoints

were further analyzed using a mixed model for repeated measures (MMRM).

Under the multiplicity control rule, a trial is successful in

meeting the co-primary endpoints if the significance of each endpoint is P < 0.05, or if the significance of only one co-primary endpoint

is P < 0.025.

If only one primary endpoint is significant at an α level of 0.025, then the secondary endpoint will be evaluated

at the same level of 0.025.

The trial was successful, since the differences in the least-squares mean (LSM) change from baseline to 48

weeks between the ANAVEX ® 2-73 and placebo groups were −1.783 [95% CI, −3.314 to −0.251];

for ADAS-Cog13, and −0.456 [95% CI, −0.831 to −0.080];

(P = 0.0175) for CDR-SB in patients with early Alzheimer’s

Primary and secondary endpoints to assess

safety and both cognitive and functional efficacy, were measured through the Alzheimer’s Disease Assessment Scale – Cognitive

Subscale test (“ADAS-Cog”), Alzheimer’s Disease Cooperative Study – Activities of Daily Living (“ADCS-ADL”)

and Clinical Dementia Rating – Sum of Boxes for cognition and function (“CDR-SB”).

In addition to these endpoints, the

ANAVEX ® 2-73 Phase 2b/3 trial design incorporated pre-specified statistical analyses related to potential genomic precision

medicine biomarkers previously identified in the ANAVEX ® 2-73 Phase 2a clinical trial.

The trial was completed in mid-2022

and, in December 2022, the Company presented topline results from the Phase 2b/3 clinical trial.

All statistical analysis were performed

by outside consultancy companies.

Furthermore, all pre-specified

clinical endpoints were analyzed using a mixed model for repeated measures (MMRM).

Under the multiplicity control rule, a trial is successful

in meeting the co-primary endpoints if the significance of each endpoint is P < 0.05, or if the significance of only one co-primary

endpoint is P < 0.025.

If only one primary endpoint is significant at an α level of 0.025, then the secondary endpoint will be

evaluated at the same level of 0.025.

The trial was successful, since the differences in the least-squares mean (LSM) change from baseline

to 48 weeks between the ANAVEX ® 2-73 and placebo groups for ADAS-Cog13 was significant at a level of P < 0.025 and for

CDR-SB was significant at a level of P < 0.025, in the patients with early Alzheimer’s disease.

comparison of individual dose groups vs placebo also supports blarcamesine’s efficacy.

For the primary endpoint ADAS-Cog13, blarcamesine

is significantly better than placebo for both the 50 mg (−2.149;

P = 0.021) and the 30 mg (−1.934;

P = 0.026) blarcamesine

dosage groups at Week 48, representing that blarcamesine slowed clinical progression at 48 weeks by 38.5% and 34.6% in 50 mg and 30 mg

placebo, respectively.

The functional co-primary endpoint, ADCS-ADL, was trending in a positive direction but did not reach

significance at Week 48.

The key secondary endpoint CDR-SB was significantly improved vs.

placebo in both 50 mg (−0.465;

and 30 mg (−0.502;

P = 0.020) groups at Week 48.

CGI-I was also significantly improved vs.

placebo in both the 50 mg (−0.314;

P = 0.008) and the 30 mg (−0.248;

P = 0.024) groups at Week 48.

The findings are supported by biomarkers, including plasma Aβ42/40-ratio

and reduction of brain atrophy.

Blarcamesine significantly slowed brain atrophy in key regions of interest, including the whole brain

by 37.6%, total grey matter by 63.5%, and lateral ventricles

In the respective safety population, common treatment-emergent

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A subsequent long-term open label extension study

of ANAVEX ® 2-73, entitled the ATTENTION-AD trial was initiated for patients who have completed the 48-week Phase 2b/3 placebo-controlled

trial referenced above.

This trial extension for an additional 96 weeks is currently ongoing, and provides an opportunity to evaluate

longer term safety and efficacy of ANAVEX ® 2-73 in persons with Alzheimer’s disease.

of ANAVEX ® 2-73, referred to as the ATTENTION-AD trial, was initiated for patients who completed the 48-week Phase 2b/3

placebo-controlled trial referenced above.

This trial extension for a duration of up to 96 additional weeks was completed in June 2024.

The trial will provide additional longer-term safety and efficacy data of ANAVEX ® 2-73 in persons with Alzheimer’s

Rett Syndrome

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

The data demonstrated dose related and significant

The data demonstrated dose related significant

improvements in an array of behavioral and gait paradigms in a mouse model with an MECP2-null mutation that causes neurological symptoms

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

A high enrollment rate in the OLE of over 91% and

the high level of requests for the Compassionate Use Program (93%) provide solid numerical evidence for the reported positive Real World

Evidence (RWE) from patients with Rett syndrome under Compassionate Use Authorization.

Families whose children were previously on drug

or placebo in the placebo-controlled trial commented favorably on the improvement of their child’s daily life due to ANAVEX ® 2-73

treatment in the Compassionate Use Program.

A high enrollment rate in the Open Label Extension

(“OLE”) of over 91% and the high level of requests for the Compassionate Use Program (93%) provide solid numerical evidence

for the reported positive Real World Evidence (RWE) from patients with Rett syndrome under Compassionate Use Authorization.

Families whose

children were previously on drug or placebo in the placebo-controlled trial commented favorably on the improvement of their child’s

daily life due to ANAVEX ® 2-73 treatment in the Compassionate Use Program.

Parkinson’s Disease

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approach of targeting SIGMAR1 as a genetic biomarker in response to ANAVEX ® 2-73 may result in improved clinical outcomes.

A 48-week Open Label Extension (“OLE”)

ANAVEX2-73-PDD-EP-001 Phase 2 trial was offered to participants after completion of the double-blind placebo-controlled ANAVEX2-73-PDD-001

Phase 2 trial discussed above.

The OLE trial assessed safety, tolerability and efficacy, measuring among others, MDS-Unified Parkinson’s

Disease Rating Scale Parts I, II, III, REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), Clinical Global Impression –

Improvement (CGI-I), as well as cognitive efficacy endpoint Montreal Cognitive Assessment (MoCA) over a 48-week period.

In March 2023, we reported the preliminary

ANAVEX2-73-PDD-EP-001 OLE trial data, which demonstrated longitudinal beneficial effects of ANAVEX ® 2-73 on the

pre-specified primary and secondary objectives.

Preliminary analysis reveals that ANAVEX ® 2-73 was found to be

generally safe and well tolerated;

and safety findings in this trial were consistent with the known safety profile of

ANAVEX ® 2-73.

In respect to efficacy, across all efficacy endpoints, patients performed better while on

ANAVEX ® 2-73.

While all patients were on drug holiday due to COVID-19 between the DB EOT and the OLE Baseline, the

respective efficacy endpoints, including the MDS-UPDRS Part II + III and CGI-I, measured at the end of trial of the double-blind

study (DB EOT) and the OLE Baseline, were worsening, as expected in a progressive disease like Parkinson’s.

However, when

patients resumed daily oral ANAVEX ® 2-73 treatment, a consistent improvement was observed during the extension phase

from OLE Baseline through OLE Week 24, and OLE Week 48, respectively.

These results are consistent with the pattern observed for all

efficacy measures in the extension phase.

The two endpoints, MDS-UPDRS Part II + III and CGI-I measured in this study are the

planned primary and key secondary endpoints in our forthcoming pivotal 6-month Parkinson’s disease study.

A 48-week OLE ANAVEX2-73-PDD-EP-001 Phase 2 trial

was offered to participants after completion of the double-blind placebo-controlled ANAVEX2-73-PDD-001 Phase 2 trial discussed above.

The OLE trial assessed safety, tolerability and efficacy, measuring among others, MDS-Unified Parkinson’s Disease Rating Scale Parts

I, II, III, REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), Clinical Global Impression – Improvement (CGI-I), as well

as cognitive efficacy endpoint Montreal Cognitive Assessment (MoCA) over a 48-week period.

In March 2023, we reported the preliminary ANAVEX2-73-PDD-EP-001

OLE trial data, which demonstrated longitudinal beneficial effects of ANAVEX ® 2-73 on the pre-specified primary and secondary

Preliminary analysis reveals that ANAVEX ® 2-73 was found to be generally safe and well tolerated, and safety

findings in this trial were consistent with the known safety profile of ANAVEX ® 2-73.

In respect to efficacy, across all

efficacy endpoints, patients performed better while on ANAVEX ® 2-73.

While all patients were on drug holiday due to COVID-19

between the DB EOT and the OLE Baseline, the respective efficacy endpoints, including the MDS-UPDRS Part II + III and CGI-I, measured

at the end of trial of the double-blind study (DB EOT) and the OLE Baseline, were worsening, as expected in a progressive disease like

However, when patients resumed daily oral ANAVEX ® 2-73 treatment, a consistent improvement was observed

during the extension phase from OLE Baseline through OLE Week 24, and OLE Week 48, respectively.

These results are consistent with the

pattern observed for all efficacy measures in the extension phase.

The two endpoints, MDS-UPDRS Part II + III and CGI-I measured in this

study are the planned primary and key secondary endpoints in our forthcoming pivotal 6-month Parkinson’s disease study.

In January 2021, we were awarded a research grant

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

our data also demonstrates that ANAVEX ® 2-73 has the potential to provide 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.

our data also demonstrates that ANAVEX ® 2-73 has the potential to provide protection for oligodendrocytes and oligodendrocyte

precursor cells (“OPCs”), 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

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to two broad categories and several specific indications, including:

Central Nervous System Diseases

Alzheimer’s disease – In 2023, an estimated 6.7 million Americans aged 65 and older suffered from Alzheimer’s disease.

The Alzheimer’s Association ® estimates that the annual number of new cases of Alzheimer’s and other dementias is projected to double by 2050.

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.

We believe that 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 currently is estimated to afflict more than 10 million people worldwide, typically middle-aged and elderly people.

Central Nervous System Di seases

Alzheimer’s disease

– In 2024, an estimated 6.9 million Americans are suffering from Alzheimer’s disease according to the Alzheimer’s

Association ® .

The Alzheimer’s Association ® estimates that the annual number of new cases of Alzheimer’s

and other dementias is projected to double by 2050.

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.

We believe that 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

Parkinson’s disease currently is estimated to afflict more than 10 million people worldwide, typically middle-aged

and elderly people.

The Parkinson’s disease market is expected to reach $11.5 billion by 2029, according to GlobalData.

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 leads to severe disruptions in neuronal homeostasis.

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

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.

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 MECP2 gene.

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.

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

Schizophrenia - Schizophrenia is a persistent and often disabling mental illness impacting how a person thinks, feels, and behaves, and affects nearly 24 million people worldwide, including 2.8 million people in the U.S., according to the World Health Organization.

It is characterized by three symptom domains:

positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from others), and cognitive impairment (deficits in memory, concentration, and decision-making).

In part due to limitations with current treatments, people living with schizophrenia often struggle to maintain employment, live independently, and manage relationships.

While current treatments can be effective in managing select symptoms, approximately 30% of people do not respond to therapy, with an additional 50% experiencing only a partial improvement in symptoms or unacceptable side effects, according to the World Health Organization.

· Fragile X – Fragile X syndrome (FXS) is the most prevalent genetic form of intellectual disability

Schizophrenia - Schizophrenia

is a persistent and often disabling mental illness impacting how a person thinks, feels, and behaves, and affects nearly 24 million

people worldwide, including 2.8 million people in the U.S., according to the World Health Organization.

It is characterized by three

symptom domains:

positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from

others), and cognitive impairment (deficits in memory, concentration, and decision-making).

In part due to limitations with current

treatments, people living with schizophrenia often struggle to maintain employment, live independently, and manage relationships.

While current treatments can be effective in managing select symptoms, approximately 30% of people do not respond to therapy, with

an additional 50% experiencing only a partial improvement in symptoms or unacceptable side effects, according to the World Health

Organization.

X – Fragile X syndrome (FXS) is the most prevalent genetic form of intellectual disability

and autism spectrum disorder, primarily affecting boys.

As with most neurodevelopmental disorders, FXS is considered a condition of synaptic

development and function.

The disease has a range of clinical presentations depending on the specific genetic changes associated with

an “expansion” of the FMR1 gene.

The disease is characterized by deficits in long-term potentiation and homeostatic plasticity.

As with most neurodevelopmental disorders,

FXS is considered a condition of synaptic development and function.

The disease has a range

of clinical presentations depending on the specific genetic changes associated with an “expansion”

of the FMR1 gene.

The disease is characterized by deficits in long-term potentiation and

homeostatic plasticity.

FXS has been detected in all populations and ethnic groups.

Researchers do not know the exact number for how many Americans could have

full mutation FXS.

Studies estimate that the disease affects approximately 1:4,000 males and 1:6,000-8,000 females.

Worldwide, more than

1,400,000 people could be affected by FXS.

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

The global antidepressant drug market is projected to reach $21 billion by 2030 according to Allied Market Research.

Pharmaceutical treatment for depression has been historically dominated by blockbuster brands.

However, the dominance of the leading brands is waning, largely due to an increase in the number of approvals for antidepressant drugs.

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

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 medications that are 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.

do not know the exact number for how many Americans could have full mutation FXS.

estimate that the disease affects approximately 1:4,000 males and 1:6,000-8,000 females.

Worldwide, more than 1,400,000 people could be affected by FXS.

Depression – Depression

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

The global antidepressant drug market is projected

to reach $21 billion by 2030 according to Allied Market Research.

Pharmaceutical treatment for depression has been historically dominated

by blockbuster brands.

However, the dominance of the leading brands is waning, largely due to an increase in the number of approvals

for antidepressant drugs.

Epilepsy – Epilepsy

is a common chronic neurological disorder characterized by recurrent unprovoked seizures.

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 medications that are 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

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 a large majority of skin cancer deaths.

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

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 a large majority of skin cancer deaths.

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 $7.5 billion by 2029.

Prostate Cancer – Specific to men, prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system.

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 $10.1 billion by the end of 2030 according to Market Research Future.

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

In the United States, approximately 62,000 new cases of pancreatic cancer will be diagnosed this year and approximately 50,000 patients will die as a result of their cancer, according to the American Cancer Society.

Sales predictions by Market Data Forecast predict that the market for the global pharmaceutical treatment of pancreatic cancer will increase to $3.7 billion by 2027.

the worldwide malignant melanoma market is expected

to grow to $7.5 billion by 2029.

Prostate Cancer –

Specific to men, prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system.

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 $10.1 billion by the end of 2030 according to Market Research Future.

Pancreatic Cancer –

Pancreatic cancer is a malignant neoplasm of the pancreas.

In the United States, approximately 62,000 new cases of pancreatic cancer

will be diagnosed this year and approximately 50,000 patients will die as a result of their cancer, according to the American Cancer

Sales predictions by Market Data Forecast predict that the market for the global pharmaceutical treatment of pancreatic

cancer will increase to $3.7 billion by 2027.

Patents, Trademarks and Intellectual Property

We hold ownership or exclusive rights to twenty-five

patents, twenty-four U.S.

patents, twenty-five U.S.

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

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second of these three 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 ® .

with (i) ANAVEX ® 19-144,

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

The third of these three

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expenses and professional services.

Comparison of the three and six months ended March

Comparison of the three and nine months ended June

30, 2024 and 2023

Operating Expenses

Total operating expenses for the quarter ended March

31, 2024 were $12.5 million, compared to $14.2 million for the comparable quarter ended March 31, 2023.

Total operating expenses for the quarter ended June

30, 2024 were $14.7 million, compared to $13.5 million for the comparable quarter ended June 30, 2023.

Total operating expenses for the

six-month period ended March 31, 2024 were $23.8 million, compared to $29.6 million for the comparable six month period ended March 31,

nine-month period ended June 30, 2024 were $38.5 million, compared to $43.1 million for the comparable nine-month period ended June 30,

Our research and development expenses for the three

months ended March 31, 2024 were $9.7 million, as compared to $11.3 million for the three months ended March 31 2023.

Our research and

development expenses for the six months ended March 31, 2024 were $18.4 million, as compared to $23.4 million for the comparable six month

period ended March 31 2023.

The decrease in research and development expenses

during the three- and six-month periods is primarily related to the following;

(i) a decrease in stock-based compensation expense of $1.0 million in the three-month period and $3.3 million

in the six-month period, as a result of the vesting of previous option awards and the extended timeline of milestone based vesting awards.

(ii) a decrease of approximately $1.3 million in the three-month period and $2.1 million in the six-month period

in expenditures over the comparable periods relating to our Rett syndrome program as a result of the completion of the EXCELLENCE trial

and the respective extension trial under the AVATAR trial.

(iii) a decrease of approximately $1.1 million in the six-month period in expenditures over the comparable period

relating to our Alzheimer’s program as a result of the completion of the Phase 2b/3 clinical trial in the comparable period.

These decreases were partially offset by an increase

of $0.5 million in both the three- and six-month periods relating to expenditures on the ANAVEX ® 3-71-SZ-001 clinical trial,

which trial commenced in the current period.

months ended June 30, 2024 were $11.9 million, as compared to $10.3 million for the three months ended June 30, 2023.

The increase in

research and development expenses during the three-month period is primarily related to the following:

(i) an increase in personnel costs of $1.3 million mostly related to the addition of several new consultants

engaged to assist in the preparation of the submission of our Marketing Authorisation Application (MAA) to the European Medicines Agency

(ii) an increase of approximately $2.6 million over the comparable period relating to manufacturing activities

of ANAVEX ® 2-73 for potential commercial use, and to support the MAA;

(iii) an increase of $0.9 million over the comparable period relating to expenditures on the ANAVEX ® 3-71-SZ-001

clinical trial, which trial commenced in the second quarter of fiscal 2024.

These increases were partially offset by (i) a decrease

in stock-based compensation expense of $0.9 million in the three-month period, as a result of the vesting of previous option awards (ii)

a decrease of approximately $1.0 million in the three-month period relating to our Rett syndrome program as a result of the completion

of the EXCELLENCE trial and the respective open label extension of the AVATAR trial and (iii) a decrease of approximately $0.9 million

in the three-month period in expenditures over the comparable period relating to our Alzheimer’s program, as a result of the completion

of the Phase 2b/3 clinical trial.

Our research and development expenses for the nine

months ended June 30, 2024 were $30.3 million, as compared to $33.7 million for the comparable nine month period ended June 30, 2023.

The decrease in research and development expenses during the nine-month period is primarily related to the following:

(i) a decrease in stock-based compensation expense of $4.2 million in the nine-month period, as a result of

the vesting of previous option awards and the extended timeline of milestone based vesting awards;

(ii) a decrease of approximately $3.1 million in the nine-month period in expenditures over the comparable

periods relating to our Rett syndrome program as a result of the completion of the EXCELLENCE trial and the respective open label extension

of the AVATAR trial;

(iii) a decrease of approximately $2.3 million in the nine-month period in expenditures over the comparable

periods relating to our Alzheimer’s program as a result of the completion of the Phase 2b/3 clinical trial.

These decreases were partially offset by (i) an increase

of $1.4 million in nine-month period relating to expenditures on the ANAVEX ® 3-71-SZ-001 clinical trial, which trial commenced

in the second quarter of fiscal 2024, (ii) an increase of $1.2 million over the comparable period relating to startup costs associated

with our planned Phase 2/3 clinical trial in Parkinson’s disease, (iii) an increase of approximately $2.8 million over the comparable

period relating to manufacturing activities of ANAVEX ® 2-73 for potential commercial use and to the support the MAA and

(iv) an increase of approximately $1.2 million related to the addition of several new consultants engaged to assist in the preparation

for the submission of our MAA.

The following table summarizes our research and development

expenses for the three- and six-months ended March 31, 2024 (in thousands):

Three months ended

Six months ended

expenses for the three- and nine-months ended June 30, 2024 (in thousands):

Three months ended June 30,

Nine months ended June 30,

Cost of external service providers

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Total research and development costs

During the three- and six-months ended March 31, 2024

During the three- and nine-months ended June 30, 2024

and 2023, external service providers cost by product candidate was as follows (in thousands):

Three months ended

Six months ended

Three months ended June 30,

Nine months ended June 30,

ANAVEX ® 2-73

4 unchanged sentences

General and administrative expenses were $2.9 million

for the three months ended March 31, 2024, as compared to $2.9 million for the same quarter of fiscal 2023.

for the three months ended June 30, 2024, as compared to $3.2 million for the same quarter of fiscal 2023.

General and administrative

expenses were $5.4 million for the six months ended March 31, 2024, as compared to $6.2 million for the same period of fiscal 2023.The

expenses were $8.3 million for the nine months ended June 30, 2024, as compared to $9.4 million for the same period of fiscal 2023.

primary reason for the decrease in general and administrative expenses was a reduction in stock-based compensation charges of $0.5 million

for the three month period and $1.1 million for the six month period, as a result of the vesting of previous option awards and the extended

for the three month period and $1.5 million for the nine month period, as a result of the vesting of previous option awards and the extended

timeline of milestone based vesting awards.

We expect to see our research and development expenditures

increase from current levels as we advance our clinical programs, including ongoing extension trials of our Alzheimer’s and Rett

syndrome programs, advancement of ANAVEX ® 3-71 trial in Schizophrenia, planned advancement of ANAVEX ® 2-73

for Parkinson’s disease, planned initiation of an ANAVEX ® 2-73 for a Fragile X clinical trial, and as we continue

to add additional staffing to manage and support these clinical initiatives.

increase from current levels as we advance our clinical programs, including advancement of ANAVEX ® 3-71 trial in Schizophrenia,

preparation of our MAA submission to the EMA, planned advancement of ANAVEX ® 2-73 for Parkinson’s disease, planned

initiation of an ANAVEX ® 2-73 for a Fragile X clinical trial, and as we continue to add additional staffing to manage and

support these clinical initiatives.

Other income (net)

The net amount of other income for the three months

ended March 31, 2024 was $2.1 million as compared to $1.1 million for the comparable three months ended March 31, 2023.

The net amount

of other income for the six months ended March 31, 2024 was $4.8 million as compared to $3.5 million for the comparable six month period

ended March 31, 2023.

The increase in other income for the quarter is primarily related to a one-time financing charge of $0.9 million

recognized in the comparable three- and six-month periods associated with entering into the 2023 Purchase Agreement (as described below).

Net loss for the three months ended March 31, 2024,

ended June 30, 2024 was $2.4 million as compared to $2.3 million for the comparable three months ended June 30, 2023.

The net amount of

other income for the nine months ended June 30, 2024 was $7.3 million as compared to $5.8 million for the comparable nine month period

ended June 30, 2023.

The increase in other income for the year-to-date period is primarily related to a one-time financing charge of $0.9

million recognized in the comparable nine-month periods associated with entering into the 2023 Purchase Agreement (as described below),

and an increase in interest income associated with an increase in interest rates.

Net loss for the three months ended June 30, 2024,

was $12.2 million, or $0.14 per share, as compared to $11.3 million, or $0.14 per share in the comparative quarter of fiscal 2023.

net loss for the six months ended March 31, 2024 was $19.2 million, or $0.23 per share, as compared to $26.1 million, or $0.33 per share

in the comparative six month period.

The decrease in net loss for the quarter is primarily related to a decrease in research and development

expenditures and an increase in other income, as discussed above.

net loss for the nine months ended June 30, 2024 was $31.4 million, or $0.38 per share, as compared to $37.4 million, or $0.47 per share

in the comparative nine month period.

The decrease in net loss for the year-to-date period is primarily related to a decrease in research

and development expenditures and an increase in other income, as discussed above.

Liquidity and Capital Resources

Working Capital (in thousands)

March 31, 2024

September 30, 2023

2 unchanged sentences

Working Capital

At March 31, 2024, we had net current assets of $144.5

million, a decrease of $10.0 million from September 30, 2023.

The decrease in net current assets primarily relates to a decrease in cash

and cash equivalents of $11.6 million due to cash utilized in operations, partially offset by $7.2 million in cash generated under the

2023 Purchase Agreement.

Over the period, our net working capital position decreased by $6.9 million to $135.0 million.

During the first six months of fiscal 2024, we utilized

On June 30, 2024, we had net current assets of $141.5

million, a decrease of approximately $12.9 million from our year ended September 30, 2023.

The decrease in net current assets primarily

relates to cash utilized in operations, partially offset by $11.9 million in cash generated under the 2023 Purchase Agreement.

During the first nine months of fiscal 2024, we utilized

cash and cash equivalents of $24.2 million to fund our operations, compared to $21.9 million during the same period of fiscal 2023.

cash position was $139.4 million at March 31, 2024 compared to $151.0 million at our fiscal year ended September 30, 2023.

cash position was $138.8 million on June 30, 2024 compared to $151.0 million at our fiscal year ended September 30, 2023.

continue to use our capital resources to advance our clinical trials for ANAVEX ® 2-73 and ANAVEX ® 3-71, and

1 unchanged sentence

The following

table summarizes cash flows during the six months ended March 31, 2024 and 2023 (in thousands):

Net cash flows used in operating activities

Net cash flows from financing activities

Increase/ (decrease) in cash and cash equivalents

table summarizes cash flows during the nine months ended June 30, 2024 and 2023 (in thousands):

cash flows used in operating activities

cash flows from financing activities

(decrease) in cash and cash equivalents

Cash flow used in operating activities

Net cash used in operating activities for the six

months ended March 31, 2024 was $19.0 million, compared to $14.3 million during the comparable period ended March 31, 2023.

Net cash used in operating activities for the nine

months ended June 30, 2024 was $24.2 million, compared to $21.9 million during the comparable period ended June 30, 2023.

The principal

reason for this increase in net cash used in operating activities in the current period is due to a net decrease (pay down) of $3.0 million

in accounts payable and accrued liabilities during the six-month period ended March 31, 2024, as compared to a net increase of $3.3 million

in accounts payable and accrued liabilities in the comparable six-month period.

reason for this is an increase in net cash expenses, after taking into account non-cash stock-based compensation, over the comparable

period of approximately $0.7 million, as well as positive changes in other working capital accounts in the current nine-month period,

as compared to the comparable nine-month period.

Cash flow provided by financing activities

Cash provided by financing activities for the six-month

period ended March 31, 2024 was $7.3 million, compared to $18.6 million during the comparable six-month period ended March 31, 2023.

Cash provided by financing activities for the nine-month

period ended June 30, 2024 was $11.9 million, compared to $27.6 million during the comparable nine-month period ended June 30, 2023.

provided by financing activities in both periods is primarily attributable to cash received from the issuance of common shares at various

32 unchanged sentences

the “commitment shares”), when and if, Lincoln Park purchased, at the Company’s discretion, the $150.0 million aggregate

During the six-month period ended March 31, 2024,

the Company issued to Lincoln Park an aggregate of 1,503,707 shares of Common Stock under the 2023 Purchase Agreement, including 1,500,000

shares of Common Stock for an aggregate purchase price of $7,411,700 and 3,707 commitment shares.

During the six-month period ended March

During the nine-month period ended June 30, 2024,

the Company issued to Lincoln Park an aggregate of 2,455,646 shares of Common Stock under the 2023 Purchase Agreement, including 2,450,000

2,075,000 shares of Common Stock for an aggregate purchase price of $18,152,000, 9,080 commitment shares as well as the 75,000 initial

commitment shares.

At March 31, 2024, an amount of $114.7 million remained

shares of Common Stock for an aggregate purchase price of $11.3 million and 5,646 commitment shares.

During the nine-month period ended

June 30, 2023, the Company issued to Lincoln Park an aggregate of 3,138,348 shares of Common Stock under the 2023 Purchase Agreement,

including 3,125,000 shares of Common Stock for an aggregate purchase price of $26.7 million and 13,348 commitment shares as well as the

75,000 initial commitment shares.

On June 30, 2024, an amount of $110.8 million remained

available under the 2023 Purchase Agreement.

3 unchanged sentences

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

pursuant to which we could 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, applicable state and federal law, and rules and regulations

and the rules of Nasdaq.

We have agreed to pay the Sales Agents’ commissions

and subject to the terms and conditions of the 2020 Sales Agreement, the Sales Agents could 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.

We were not obligated to make any sales of shares under the 2020 Sales Agreement.

We or the Sales Agents could suspend

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

The Sales Agents would act as agents

on a commercially reasonable efforts basis consistent with their normal trading and sales practices, applicable state and federal law,

and rules and regulations and the rules of Nasdaq.

We agreed to pay the Sales Agents’ commissions

for their services of 3.0% of the gross proceeds from the sale of shares of Common Stock pursuant to the 2020 Sales Agreement.

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

No shares were sold during the six months ended March

No shares were sold during the nine months ended June

30, 2024 and 2023 under the 2020 Sales Agreement.

The Company currently is unable to sell shares of Common Stock under the Sales Agreement.

The Company terminated the 2020 Sales Agreement on July 24, 2024.

Off-Balance Sheet Arrangements

20 unchanged sentences

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