What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2025-11-25 compared with 2024-12-23 · 487 added, 443 removed, 1080 unchanged (46% of the section changed)

6 unchanged sentences

clinical trials.

Our focus is on developing innovative

The Company’s focus is on developing innovative

treatments for Alzheimer’s disease, Parkinson’s disease, schizophrenia, neurodevelopmental, neurodegenerative, and rare diseases,

including Rett syndrome, and other central nervous system (CNS) disorders.

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.

Our research and development pipeline includes ANAVEX ® 2-73

currently in three different clinical trial indications, and ANAVEX ® 3-71 currently in one clinical trial and several other

compounds in different stages of clinical and pre-clinical development.

The following table summarizes key information about our programs:

2 unchanged sentences

receptor (SIGMAR1) binding activities.

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

important roles in cellular communication.

SIGMAR1 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 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.

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)

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 SIGMAR1 could also play a role in modulating

the cellular response to viral infection and ameliorate pathogenesis.

The SIGMAR1 gene encodes the SIGMAR1 protein, which

is an intracellular chaperone protein with important roles in cellular communication.

SIGMAR1 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 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.

Reyes S et al., Sci Rep.

2021 Aug 25;11(1):17150

Cellular Homeostasis

19 unchanged sentences

delay neurodevelopmental and neurodegenerative disease progression.

ANAVEX ® 2-73 (blarcamesine)-specific

As part of some of our clinical trials, we have incorporated

a genomic analysis to better understand potential populations for whom our clinical programs might benefit.

In our clinical trials, a

full genomic analysis of Alzheimer’s disease patients treated with ANAVEX ® 2-73 (blarcamesine) has helped us identify

actionable genetic variants.

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

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.

We believe 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

(blarcamesine), which are considered independent of Alzheimer’s disease pathology, as well as multiple endpoints and time-points,

provides support for the potential precision medicine clinical development of ANAVEX ® 2-73 (blarcamesine) by using genetic

biomarkers identified within the trial population itself to either confirm the mechanism of action of ANAVEX ® 2-73 (blarcamesine)

or target patients who are most likely to respond to ANAVEX ® 2-73 (blarcamesine) treatment.

We may in the future utilize

such an approach in Alzheimer’s disease as well as indications like Parkinson’s disease dementia in which ANAVEX ® 2-73

(blarcamesine) is currently being studied.

Clinical Trials Overview

Clinical Program Overview

ANAVEX®2-73 (blarcamesine)

We believe ANAVEX ® 2-73 may offer a

disease-modifying approach in neurodegenerative and neurodevelopmental diseases by activation of SIGMAR1.

ANAVEX ® 2-73 is

being developed as well as an oral once-daily capsule formulation for diseases such as Alzheimer’s disease and Parkinson’s

disease, and in an oral liquid once-daily formulation for rare diseases such as Rett syndrome and Fragile X.

Alzheimer’s Disease

16 unchanged sentences

trial have allowed participants who completed the 52-week Part B of the trial 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

an opportunity to gather extended safety data for a cumulative 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’s compassionate use Special Access Scheme.

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

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

The Phase 2b/3 trial enrolled 508 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 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.

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

All statistical

analyses 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,

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.

In July 2018, we presented

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

More than 33,000 genes were analyzed

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

with ANAVEX ® 2-73.

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

them variants related to the SIGMAR1, the target for ANAVEX ® 2-73.

Results showed that trial participants with the common

SIGMAR1 wild type gene variant, which is estimated to be about 80% of the population worldwide, demonstrated improved cognitive (MMSE)

and functional (ADCS-ADL) scores.

The results from this evaluation supported the continued evaluation of genomic information in subsequent

clinical trials, since these signatures can now be applied to neurological indications tested in future clinical trials with ANAVEX ® 2-73

including Alzheimer’s disease, Parkinson’s disease dementia and Rett syndrome.

ANAVEX ® 2-73

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

This larger Phase 2b/3 double-blind,

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

The trial enrolled

508 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

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.

statistical analyses 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

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, 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.

The comparison of individual dose groups vs placebo

26 unchanged sentences

9 (5.6%) during maintenance with placebo.

In November 2024, we announced the submission of a

Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for ANAVEX ® 2-73 for the treatment of

Alzheimer's disease and, in December 2024, the EMA accepted the submission for scientific review.

The MAA, if approved, would allow direct

market access throughout the European Union for oral ANAVEX ® 2-73 (blarcamesine) for the treatment of Alzheimer’s

A subsequent long-term open label extension study

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.

In November 2024, we announced the submission of a Marketing Authorisation

Application (“MAA”) to the European Medicines Agency (EMA), under the centralized procedure, for ANAVEX ® 2-73

for the treatment of Alzheimer’s disease and, in December 2024, the EMA accepted the submission for scientific review.

if approved, would allow direct market access throughout the European Union for oral ANAVEX ® 2-73 (blarcamesine) for the

treatment of Alzheimer’s disease.

A company seeking to market a new pharmaceutical product through the centralized procedure must

file safety data and efficacy data as part of the MAA.

After the EMA evaluates the MAA, it provides a recommendation to the European Commission

(“EC”) and the EC then approves or denies the MAA.

On November 14, 2025, we announced that we were informed by the Committee

for Medicinal Products for Human Use (CHMP) of the EMA of a negative trend vote on the MAA following an oral explanation.

expected to adopt a formal opinion on the MAA at its December 2025 meeting.

We plan to request a re-examination of the CHMP opinion

upon its formal adoption.

A long-term open label extension study 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 96/144 additional weeks was completed in June 2024.

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

Alzheimer’s disease.

The trial extension demonstrated that

blarcamesine-treated patients continued to accrue benefit through up to 192 weeks, as measured by the clinical endpoints ADAS-Cog13

(LS mean difference -3.83;

P = 0.0165) and ADCS-ADL (LS mean difference +4.30, P = 0.0206).

No new safety findings were observed with

continued blarcamesine treatment over three years, confirming good comparative safety profile and no associated neuroimaging

adverse events.

Delayed-start analysis of treatment with oral blarcamesine was significant, reflecting the importance of early treatment initiation.

Additional precision medicine population 48-week data

demonstrates cognitive stabilization in early Alzheimer’s disease.

Cognitive outcomes observed in the oral blarcamesine 30 mg precision

medicine cohort move toward normal aging profiles across validated clinical scales.

For ADAS-Cog13, blarcamesine showed a 48-week change

from baseline of 0.853 compared to ~1 point typical annual decline in prodromal (pre-dementia) aging adults.

For CDR-SB, blarcamesine

demonstrated a change from baseline of 0.465, aligning with the 0-0.5 point annual range seen in prodromal aging.

These data are similar

to referenced barely detectable prodromal Alzheimer’s disease decline, in spite of the more advanced stage of Alzheimer’s

disease impairment at baseline of the blarcamesine population.

posthoc analysis demonstrates continued long-term benefit from oral blarcamesine compared to decline observed in the Alzheimer’s

Disease Neuroimaging Initiative (ADNI) control group.

Externally matched control participants from the ADNI database were compared with

participants over the 144-week period of ANAVEX Ò 2-73-AD-004

and its ATTENTION-AD (ANAVEX Ò 2-73-AD-EP-004)

open-label extension (OLE) Phase IIb/III trial.

[1] For ADAS-Cog13, total score ranges

from 0 to 85 with higher scores indicating increased cognitive impairment.

Observed raw data was used.

Scheduled visits were [OLE Week 0 = Combined Week 48], [OLE Week 48 = Combined

Week 96], [OLE Week 96 = Combined Week 144];

Combined = DB (double-blind) + OLE (open-label-extension) trials.

Up to 144 weeks ADNI control

group data was available.

In the intent-to-treat (ITT) population, significantly

less cognitive decline was observed for the blarcamesine participants compared to the ADNI control group at 48 weeks with a significant,

and clinically meaningful difference in mean change from baseline ADAS-Cog13 total score of −2.68 points ( p < 0.0001).

Over the course of the open-label extension study

at time point 96 weeks, these two groups diverged sharply, with statistically significant differences in mean change in ADAS-Cog13 total

score at 96 weeks of −6.41 points ( p < 0.0001).

The difference between groups continues to increase at 144 weeks (ADAS-Cog13

total score difference of −12.78 points;

The results provide evidence of the significant beneficial

therapeutic effect of blarcamesine, which positively separates from the ADNI control group with duration of treatment.

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.

The study was funded by the Michael J.

Fox Foundation.

Additional data announced in

October 2017 indicated that ANAVEX ® 2-73 induced robust neurorestoration in experimental Parkinsonism.

We believe the encouraging

results we have gathered in this preclinical model, coupled with the favorable profile of this product candidate in the Alzheimer’s

disease trial, support the notion that ANAVEX ® 2-73 has the potential to treat 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 in Spain and Australia,

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

The trial enrolled approximately

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

The ANAVEX ® 2-73

Phase 2 Parkinson’s disease dementia trial design incorporated genomic precision medicine biomarkers identified in the ANAVEX ® 2-73

Phase 2a Alzheimer’s disease trial.

The trial demonstrated that ANAVEX ® 2-73

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

The results showed 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-Unified Parkinson’s Disease Rating Scale (“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 capability

of slowing and reversing symptoms that progress in Parkinson’s disease.

In addition, the trial confirmed the precision medicine

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

[2] ADAS-Cog13 scores

LS mean difference between the treatment groups being larger than 2 points are considered clinically meaningful improvements:

Hill MD, Black SE, Smith EE.

Minimal clinically important difference in Alzheimer's disease:

Rapid review.

Alzheimers Dement.

2024;20(5):3352-3363.

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), 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.

We anticipate conducting further clinical trials of

ANAVEX ® 2-73 in Parkinson’s disease dementia after submitting the results of the trial to regulatory authorities to

obtain regulatory guidance.

Also with respect to Parkinson’s disease, in

January 2021, we were awarded a research grant of $1.0 million from The Michael J.

Fox Foundation for Parkinson’s Research to

explore utilization of PET imaging biomarkers to enable measurement of target engagement and pathway activation of the SIGMAR1 with clinically

relevant doses including in people with Parkinson’s disease.

This study is currently in the planning stage.

Rett Syndrome

4 unchanged sentences

that mimic Rett syndrome.

The study was funded by the International Rett Syndrome Foundation (“Rettsyndrome.org”).

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.

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.

trials were conducted in a range of patient age demographics and geographic regions, utilizing an oral liquid once-daily formulation

of ANAVEX ® 2-73.

The first Phase 2 trial, (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, PK and efficacy trial 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 was safety.

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

All secondary

efficacy endpoints of the trial showed statistically significant and clinically meaningful response in the Rett Syndrome Behaviour Questionnaire

(“RSBQ”) response, when compared to placebo, in the intent to treat (“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 CGI-I response throughout the 7-week clinical trial, when compared to placebo in the ITT cohort (all participants, p =

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.

No other clinical trials with

ANAVEX ® 2-73 related to Rett syndrome have been conducted in the United States.

The study was funded by the International Rett Syndrome Foundation.

Our Rett syndrome program includes several clinical trials that were conducted

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

The FDA has granted Orphan Drug Designation and the Rare Pediatric Disease (RPD) designation for the treatment of Rett syndrome.

designation is intended to encourage the development of treatments for rare pediatric diseases.

Additionally, the FDA has 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.

An earlier application for a proposed Rett syndrome study in the United States resulted in

the FDA requesting additional information.

The resulting clinical hold and subsequent partial clinical hold have since been removed after

the Company satisfactorily provided the additional information requested.

The following is a summary of clinical trials conducted by the

Company in Rett syndrome.

The first Phase 2 trial, (ANAVEX ® 2-73-RS-001), took place in the United States, and was completed

in December 2020.

This trial was a randomized double-blind, placebo-controlled safety, tolerability, PK and efficacy trial 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 was safety.

The dosing of 5 mg ANAVEX ® 2-73 was

well-tolerated and demonstrated dose-proportional PK.

All secondary efficacy endpoints of the trial showed statistically significant and

clinically meaningful response in the Rett Syndrome Behaviour Questionnaire (“RSBQ”) response, when compared to placebo, in

the intent to treat (“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,

ANAVEX ® 2-73 treatment resulted in a sustained improvement in CGI-I response throughout the 7-week clinical

trial, 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.

This clinical trial was funded, in part, by a financial

grant from the International Rett Syndrome Foundation of $0.6 million.

No other clinical trials with ANAVEX ® 2-73 related

to Rett syndrome have been conducted in the United States.

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

52 unchanged sentences

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

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.

The study was funded by the Michael J.

Fox Foundation.

Additional data announced in

October 2017 indicated that ANAVEX ® 2-73 induced robust neurorestoration in experimental Parkinsonism.

We believe the encouraging

results we have gathered in this preclinical model, coupled with the favorable profile of this product candidate in the Alzheimer’s

disease trial, support the notion that ANAVEX ® 2-73 has the potential to treat 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 in Spain and Australia,

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

The Phase 2 trial enrolled

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

The ANAVEX ® 2-73 Phase 2 Parkinson’s disease dementia trial design incorporated genomic precision medicine biomarkers

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

The trial demonstrated that ANAVEX ® 2-73

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

The results showed 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-Unified Parkinson’s Disease Rating Scale (“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 capability

of slowing and reversing symptoms that progress in Parkinson’s disease.

In addition, the trial confirmed the precision medicine

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

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), 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 >6-month Parkinson’s disease study.

In January 2021, we were awarded a research grant

of $1.0 million from The Michael J.

Fox Foundation for Parkinson’s Research 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 SIGMAR1 with clinically relevant doses including in people with Parkinson’s disease.

Schizophrenia, Frontotemporal Dementia and Alzheimer’s

Other indications

We believe preclinical data from our studies also

supports further research into the use of ANAVEX ® 2-73 as a potential 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 tuberous sclerosis complex (TSC).

ANAVEX ® 2-73 demonstrated significant

improvements in all of these indications in the respective preclinical animal models.

In a preclinical 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 mice.

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

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 preclinical data observed in both neurodevelopmental and neurodegenerative

disorders like Angelman and Fragile X syndromes.

In addition, preclinical data to-date also indicates

that ANAVEX ® 2-73 has the potential to demonstrate protective effects of mitochondrial enzyme complexes during pathological

conditions, which, if impaired, may play a role in the pathogenesis of neurodegenerative and neurodevelopmental diseases.

In addition, preclinical data on ANAVEX ® 2-73

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 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

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 demonstrated that treatment

with ANAVEX ® 2-73 significantly increased survival and reduced seizures in those mice.

ANAVEX ® 2-73

(blarcamesine)-specific Biomarkers

As part of some of our clinical trials, we have incorporated

a genomic analysis to better understand potential populations for whom our clinical programs might benefit.

A full genomic analysis of

Alzheimer’s disease patients treated with ANAVEX ® 2-73 (blarcamesine) has helped us identify actionable genetic variants.

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

We believe 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 (blarcamesine),

which are considered independent of Alzheimer’s disease pathology, as well as multiple endpoints and time-points, provides support

for the potential precision medicine clinical development of ANAVEX ® 2-73 (blarcamesine) by using genetic biomarkers identified

within the trial population itself to either confirm the mechanism of action of ANAVEX ® 2-73 (blarcamesine) or target patients

who are most likely to respond to ANAVEX ® 2-73 (blarcamesine) treatment.

We may in the future utilize such an approach in

certain indications in which ANAVEX ® 2-73 (blarcamesine) is being studied.

ANAVEX ® 3-71

ANAVEX ® 3-71 is an orally available

clinical drug candidate with a novel mechanism of action via SIGMAR1 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.

We believe it is effective 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 SIGMAR1 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.

The FDA has granted Orphan Drug Designation to ANAVEX ® 3-71 for the

treatment of Frontotemporal Demetia (“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.

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

to demonstrate 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-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.

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

A total of 36 healthy male and female

subjects were included.

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

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

The Phase 1 clinical trial was a prospective double-blind,

randomized, placebo-controlled trial conducted in Australia.

A total of 36 healthy male and female subjects were included.

Single escalating

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

and the effects of food and gender on its PK in healthy volunteers.

The trial met

29 unchanged sentences

Based on these

results, and ANAVEX ® 3-71’s pre-clinical profile, we intend to advance ANAVEX ® 3-71 into a biomarker-driven

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 schizophrenia, FTD and Alzheimer’s disease, evaluating longitudinal effect

of treatment with ANAVEX ® 3-71.

The first of these trials is being conducted in schizophrenia.

Schizophrenia

20 unchanged sentences

negative, and cognitive symptoms of schizophrenia.

The currently

ongoing Part B of the placebo-controlled Phase 2 study, which includes more participants and a longer treatment duration, will provide

more comprehensive data on the efficacy and safety of ANAVEX ® 3-71 in schizophrenia.

Our research and development pipeline includes ANAVEX ® 2-73

currently in three different clinical trial indications, and ANAVEX ® 3-71 currently in one clinical trial and several other

compounds in different stages of clinical and pre-clinical development.

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 SIGMAR1 could play a role in modulating the cellular response to viral infection and ameliorate

pathogenesis.

Compounds that have been subjects of our research

include the following:

ANAVEX ® 2-73 (blarcamesine)

We believe ANAVEX ® 2-73 may offer a

disease-modifying approach in neurodegenerative and neurodevelopmental diseases by activation of SIGMAR1.

ANAVEX ® 2-73 is

being developed in an oral liquid once-daily formulation for rare diseases such as Rett syndrome as well as an oral once-daily capsule

formulation for diseases such as Alzheimer’s disease.

In Rett syndrome, administration of ANAVEX ® 2-73

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

disease model.

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 mice.

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

The RPD designation

is intended 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, to

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

The Phase 2 trial enrolled approximately

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

The ANAVEX ® 2-73

Phase 2 Parkinson’s disease dementia trial design incorporated genomic precision medicine biomarkers identified in the ANAVEX ® 2-73

Phase 2a Alzheimer’s disease trial.

The trial demonstrated that ANAVEX ® 2-73

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

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

significant improvements in the 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 trial to regulatory authorities to obtain regulatory guidance.

In Alzheimer’s disease 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 SIGMAR1 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 Alzheimer’s disease

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 Alzheimer’s disease.

There were no significant changes in laboratory or ECG parameters.

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 Alzheimer’s disease.

In November 2016, we completed a Phase 2a clinical

trial 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.

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

In July 2018, we presented

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

More than 33,000 genes were analyzed

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

with ANAVEX ® 2-73.

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

them variants related to the SIGMAR1, the target for ANAVEX ® 2-73.

Results showed that trial participants with the common

SIGMAR1 wild type gene variant, which is estimated to be about 80% of the population worldwide, demonstrated improved cognitive (MMSE)

and functional (ADCS-ADL) scores.

The results from this evaluation supported the continued evaluation of genomic information in subsequent

clinical trials, since these signatures can now be applied to neurological indications tested in future clinical trials with ANAVEX ® 2-73

including Alzheimer’s disease, Parkinson’s disease dementia and Rett syndrome.

ANAVEX ® 2-73

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

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 trial design incorporates inclusion of genomic precision

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

We believe preclinical data from our studies also

supports further research into the use of ANAVEX ® 2-73 as a potential 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 tuberous sclerosis complex (TSC).

ANAVEX ® 2-73 demonstrated significant

improvements in all of these indications in the respective preclinical animal models.

In a preclinical 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 mice.

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

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 preclinical data observed in both neurodevelopmental and neurodegenerative

disorders like Angelman and Fragile X syndromes.

In addition, preclinical data to-date also indicates

that ANAVEX ® 2-73 has the potential to demonstrate protective effects of mitochondrial enzyme complexes during pathological

conditions, which, if impaired, may play a role in the pathogenesis of neurodegenerative and neurodevelopmental diseases.

In addition, preclinical data on ANAVEX ® 2-73

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 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

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 demonstrated that treatment

with ANAVEX ® 2-73 significantly increased survival and reduced seizures in those mice.

ANAVEX ® 3-71

ANAVEX ® 3-71 is an orally available

clinical drug candidate with a novel mechanism of action via SIGMAR1 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.

We believe it is effective in 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 SIGMAR1 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 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.

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

to demonstrate 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 trial took place in Australia and was a double-blind, randomized, placebo-controlled, Phase

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

including effects of food and gender in healthy volunteers.

The trial 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 Trials Overview – Schizophrenia, Frontotemporal Dementia and Alzheimer’s disease .

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 schizophrenia, FTD and Alzheimer’s disease, evaluating longitudinal effect

of treatment with ANAVEX ® 3-71.

We believe the results of this clinical trial and preclinical study could serve as a basis

for advancing into respective registration trials in the U.S.

these trials, the ANAVEX ® 3-71-SZ-001 clinical trial, commenced in March 2024 and is more fully described above under

Clinical Trials Overview – Schizophrenia.

we announced the completion of enrollment of Part B of the study, which included more participants and a longer treatment duration.

top-line data of the Phase 2 ANAVEX ® 3-71-SZ-001 clinical was announced in October 2025.

The study successfully achieved

its primary endpoint, demonstrating that ANAVEX ® 3-71 was safe and well-tolerated.

The safety profile was consistent with

previous studies of ANAVEX ® 3-71 in healthy volunteers, with no serious treatment-emergent adverse events (TEAEs) and no

severe TEAEs reported in either Part A or Part B of the study.

In addition to meeting the primary safety endpoint, secondary and exploratory

analyses revealed encouraging trends in several outcome measures.

The study demonstrated positive trends in objective electroencephalography

(EEG) and event-related potential (ERP) biomarkers of schizophrenia.

Furthermore, neuroinflammatory biomarker assessments showed that

glial fibrillary acidic protein (GFAP), a marker of neuroinflammation, was reduced in participants receiving ANAVEX ® 3-71

compared to placebo.

This reduction in neuroinflammatory markers suggests a potential disease-modifying effect that may become more pronounced

with longer treatment durations.

ANAVEX ® 1-41

52 unchanged sentences

Central Nervous System Diseases

Alzheimer’s disease – In 2024, an estimated

6.9 million Americans are suffering from Alzheimer’s disease according to the Alzheimer’s Association ® .

Alzheimer’s Association ® estimates that the annual number of new cases of Alzheimer’s and other dementias is

projected to double by 2050.

Alzheimer’s disease – An estimated 7.2

million Americans aged 65 and older are living with Alzheimer’s dementia in 2025, 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

24 unchanged sentences

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.

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 34% of people do not respond to therapy, with an additional 50-60% experiencing only a partial improvement in

symptoms or unacceptable side effects.

Fragile X – Fragile X syndrome (FXS) is

the most prevalent genetic form of intellectual disability and autism spectrum disorder, primarily affecting boys.

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 34% of people do not respond to therapy, with an additional 50-60% experiencing only a partial improvement

in symptoms or unacceptable side effects.

Fragile 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

5 unchanged sentences

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.

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

1 unchanged sentence

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.

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.

4 unchanged sentences

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.

According to the Centers for Disease Control and Prevention, data from 2021 and 2022 suggest

epilepsy affects roughly 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.

1 unchanged sentence

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.

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.

1 unchanged sentence

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.

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.

16 unchanged sentences

its role in maintaining neuronal homeostasis, we believe sigma receptors show significant promise as viable targets for therapeutic molecules

in an effort to treat Alzheimer’s disease and other CNS diseases and disorders, including Parkinson’s disease and Rett syndrome,

by restoring healthy gene expression.

in an effort to treat Alzheimer’s disease and other CNS diseases and disorders by restoring healthy gene expression.

At this time, our competitors are primarily other

5 unchanged sentences

resources, an established presence in the market, expertise in research and development, manufacturing, preclinical and clinical testing,

may be in the process of obtaining regulatory approvals and marketing of approved products.

These competitors also compete with us in

recruiting and retaining qualified scientific and technical personnel, establishing clinical trial sites and patient registration for

or may be in the process of obtaining regulatory approvals and marketing of approved products.

These competitors also compete with us

in recruiting and retaining qualified scientific and technical personnel, establishing clinical trial sites and patient registration for

clinical trials, as well as in acquiring or developing technologies complementary to, or necessary for, our programs.

4 unchanged sentences

Patents, Trademarks and Intellectual Property

We hold ownership or exclusive rights to twenty-five

patents, twenty-five (25) 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.

We hold ownership or exclusive rights to thirty (30)

patents, seventeen (17) pending U.S.

patent applications, and numerous PCT and ex-U.S.

patents and patent applications relating

to our drug candidates, methods associated therewith, and to our research programs.

We own one issued U.S.

1 unchanged sentence

and certain anticholinesterase inhibitors composition and method for neuroprotection,” which claims a composition of matter of ANAVEX ® 2-73,

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

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

We own one issued U.S.

a synergistic neuroprotective compound, combined with donepezil and other cholinesterase inhibitors.

This patent is expected to expire

in June 2034, absent any patent term extension for regulatory delays.

We own another issued U.S.

patent entitled “A2-73

3 unchanged sentences

This patent is expected to expire in July 2039, absent any patent term extension for regulatory

We own four issued U.S.

We own five issued U.S.

patents each with claims directed

to crystalline forms of ANAVEX ® 2-73.

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

The first of these five 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

1 unchanged sentence

The second of these

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

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

for Alzheimer’s disease using the compositions.

1 unchanged sentence

for regulatory delays.

The third of these four 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 2036, absent

any patent term extension for regulatory delays.

The fourth of these four patents claims method of making certain crystalline forms ANAVEX ® 2-73.

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

and methods of treating 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 fourth patent claims method of making certain crystalline forms of ANAVEX ® 2-73.

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

The fifth patent claims crystalline

forms of the dihydrogen phosphate salt of ANAVEX ® 2-73 and dosage forms (including transdermal and oral dosage forms) and

pharmaceutical compositions containing the same.

This patent is expected to expire in July 2039, absent any patent term extension for

regulatory delays.

We also own three issued U.S.

30 unchanged sentences

for regulatory delays.

Further, we own one issued U.S.

patent with claims

Further, we own two issued U.S.

patents with 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.

Additionally, we own two issued U.S.

patent for the treatment of insomnia, anxiety, or

The first of the two patents claims methods of treating insomnia or anxiety with ANAVEX ® 2-73, ANAVEX ® 19-144,

and/or ANAVEX ® 1-41.

These patents are expected to expire in July 2038,

absent any patent term extension for regulatory delays.

Additionally, we own three issued U.S.

patents for the treatment of insomnia,

anxiety, or agitation.

The first of the three patents claims methods of treating insomnia or anxiety with ANAVEX ® 2-73,

ANAVEX ® 19-144, and/or ANAVEX ® 1-41.

This patent is expected to expire in September 2038.

The second of the two patents claims a dosage

form comprising any of, or any combination of ANAVEX ® 2-73, ANAVEX ® 19-144, and/or ANAVEX ® 1-41.

This patent is expected to expire in July 2038, absent any patent term extension for regulatory delays.

The second and third

of the three patents claim dosage forms comprising any of, or any combination of ANAVEX ® 2-73, ANAVEX ® 19-144,

and/or ANAVEX ® 1-41.

These patents are expected to expire in July 2037, absent any patent term extension for regulatory

In addition, we own one issued U.S.

patent with claims

directed to a method of treating Alzheimer’s disease based upon selection of particular responders to ANAVEX ® A2-73

treatment based upon the absence of certain genetic polymorphisms.

Further, we own one issued U.S.

5 unchanged sentences

patent with claims directed to pharmaceutical

dosage forms of (-) enantiomer of ANAVEX ® 2-73.

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

for regulatory delays.

dosage forms of the (-) enantiomer of ANAVEX ® 2-73.

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

extension for regulatory delays.

We also own three issued U.S.

patents related

to ANAVEX ® 1066.

The first of these three 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.

The third patent

claims dosage forms and pharmaceutical compositions comprising (+) ANAVEX ® 1066 isomer.

All three 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 three patents claims methods for treating or preventing pain using the (+) ANAVEX ® 1066 isomer.

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

The third patent claims dosage

forms and pharmaceutical compositions comprising the (+) ANAVEX ® 1066 isomer.

All three patents are expected to expire in

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

For ANAVEX ® 2-73, ANAVEX ® 19-144,

29 unchanged sentences

Government authorities in the United States, at the

federal, state and local levels, and other countries extensively regulate, among other things, the research, development, testing, manufacture,

quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, marketing and export and

import of products such as those we are developing.

A new drug must be approved by the FDA through the NDA or ANDA process before it may

be legally marketed in the United States.

We are subject to various government regulations in connection with the development of our pipeline.

federal, state and local levels, and in other countries extensively regulate, among other things, the research, development, testing,

manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, marketing

and export and import of products such as those we are developing.

A new drug must be approved by the local regulatory authority through

an NDA, MAA or other regulatory process before it may be legally marketed in each jurisdiction.

We are subject to various government regulations

in connection with the development of our pipeline.

Drug Development and Regulation

167 unchanged sentences

The FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment,

keep a deferral current or fails to submit a request for approval of a pediatric formulation.

keeps a deferral current or fails to submit a request for approval of a pediatric formulation.

If a drug receives FDA approval, the approval may

211 unchanged sentences

In the future, we may apply for restoration of patent-term for our currently owned or licensed

patents to add patent life beyond its current expiration date, depending on the expected length of the clinical trials and other factors

patents to add patent life beyond their current expiration dates, depending on the expected length of the clinical trials and other factors

involved in the filing of the relevant NDA.

Foreign Regulatory Requirements

In addition to regulations in the U.S., our business

is subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our products.

of whether it concerns an FDA approved or investigational drug, the commencement of clinical trials and the subsequent marketing of a

drug product in foreign countries are subject to preliminary approvals from the corresponding regulatory authorities of such countries.

For example, the conduct of clinical trials in the EU is governed by the Clinical Trials Regulation (EU) No 536/2014 (the “CTR”)

and the principles and guidelines on GCP.

Before any clinical trial can begin, the sponsor must

obtain approval from both a national ethics committee and the relevant National Competent Authority (NCA) in each country where the trial

will take place.

Since the implementation of the EU Clinical Trials Regulation (Regulation (EU) No.

536/2014), these applications are

submitted through the central Clinical Trials Information System (CTIS), which harmonizes and streamlines trial approvals across Member

One NCA (the reporting EU member state selected by

the sponsor) takes the lead in validating and evaluating the application, as well as consulting and coordinating with the other concerned

member states in which the clinical trial is to be conducted.

If an application is rejected, it may be amended and resubmitted through

A concerned member state may in limited circumstances declare an “opt-out” from an approval and prevent the clinical

trial from being conducted in that member state.

Once sufficient evidence has been gathered to demonstrate

that the medicine is safe and effective, a sponsor prepares a Marketing Authorisation Application (MAA).

This application includes comprehensive

information on quality, nonclinical, and clinical aspects, compiled in the Common Technical Document (CTD) format.

Most innovative medicines — particularly those

for serious or rare diseases or involving novel mechanisms of action — are evaluated through the centralised procedure, which is

administered by the European Medicines Agency (EMA).

Under this route, the EMA’s Committee for Medicinal Products for Human Use

(CHMP) conducts a scientific assessment of the application.

The evaluation process typically takes 210 active days, during which rapporteurs

and co-rapporteurs review the data and issue questions to the sponsor.

The sponsor may also be invited to an oral explanation meeting

to clarify aspects of the data or the scientific rationale supporting the application.

At the conclusion of its review, the CHMP issues an opinion — positive

or negative — on whether the medicine should be authorised.

If the CHMP issues a negative opinion, the applicant has the right to

request a re-examination within fifteen days.

In this process, new rapporteurs are appointed to reassess the case, often considering additional

analyses, such as updated clinical findings, that may address earlier concerns.

When the CHMP adopts a positive opinion, the file

is forwarded to the European Commission, which issues the final legally binding decision on marketing authorisation, typically within

A centrally granted marketing authorisation is valid in all EU Member States, as well as Iceland, Liechtenstein, and Norway.

After approval, the sponsor enters the post-authorisation

phase, which involves continuous monitoring of the medicine’s safety and efficacy through pharmacovigilance activities.

must submit periodic safety update reports, comply with Good Pharmacovigilance Practice (GVP) requirements, and may be required to conduct

post-authorisation safety or efficacy studies.

The MA can also be varied, renewed, or, in rare cases, withdrawn, depending on emerging

Failure to comply with the EU member state laws implementing

the EU Community Code on medicinal products, and EU rules governing the promotion of medicinal products, interactions with physicians,

misleading and comparative advertising and unfair commercial practices, with the EU Member State laws that apply to the promotion of medicinal

products, statutory health insurance, bribery and anti-corruption or with other applicable regulatory requirements can result in enforcement

action by the relevant EU Member State authorities.

This may include any of the following sanctions:

fines, imprisonment, orders forfeiting

products or prohibiting or suspending their supply to the market, orders to suspend, vary, or withdraw the marketing authorization or

requiring the manufacturer to issue public warnings, or to conduct a product recall.

The approval process in other countries outside the

and the EU varies from country to country, and the time may be longer or shorter than that required for the FDA approval.

the requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement for market access vary greatly

from country to country.

In all cases, clinical trials are conducted in accordance with GCP and the applicable regulatory requirements

and the ethical principles that have their origin in the Declaration of Helsinki.

Foreign Sales

150 unchanged sentences

1320a-7a, provides, in part, that the federal government may seek civil monetary penalties against any person who presents or causes to

be presented claims to a Federal health care program that the person knows or should know is for an item or services that was not provided

be presented claims to a Federal health care program that the person knows or should know is for an item or services that were not provided

as claimed or is false or fraudulent, or the person has made a false statement or used a false record to get a claim paid.

82 unchanged sentences

that Congress could pursue as well as potential administrative actions HHS can take to advance these principles.

the Inflation

In addition, the Inflation

Reduction Act (“IRA”) passed on August 16, 2022.

24 unchanged sentences

a number of highly regarded medical institutions.

We currently have approximately forty-two full-time

We currently have approximately thirty-four full-time

employees, and we retain several independent contractors on a regular or as-needed basis.

10 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-K

Item 1. Business