ANAVEX LIFE SCIENCES CORP
For the period ended Mar 31, 2025. Filed May 13, 2025.
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A company's report for each of its first three quarters. The financial statements are not audited. It shows how the business has moved since the last annual report, and what management says changed.
Mar 31, 2025 · Filed May 13, 2025
AVXL$1.15+3.6%Stored close · as of Nov 6, 2026
What changed in Management’s Discussion and Analysis?
Read the current filingPrevious report: 10-Q
Period ended 2024-12-31; filed 2025-02-12.
0001731122-25-000205
ITEM 2. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONSCurrent report: 10-Q
Period ended 2025-03-31; filed 2025-05-13.
0001731122-25-000724
ITEM 2. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONSThe baseline is this issuer’s latest earlier reporting period of the same form that was filed before the current report. A previous 10-Q is a different quarter, not a year-over-year comparison. Amendments are excluded.
Compared 160 previous paragraphs and 149 current paragraphs.
104 unchanged; 34 reworded; 9 added; 16 removed; 6 previous and 2 current paragraphs rearranged.
Tables are not compared: 12 previous and 12 current tables excluded. Dates, whitespace, punctuation and numbering changes are ignored; changes to financial figures remain significant.
A changed paragraph is not evidence that risk increased or decreased. An unchanged paragraph does not establish that risk stayed the same.
Added paragraphs (9)
Current report
Clinical Program Overview
Current report
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.
Current report
Other indications
Current report
Our research and development expenses for the three months ended March 31, 2025 were $9.9 million, as compared to $9.7 million for the three months ended March 31, 2024. Our research and development expenses for the six months ended March 31, 2025 were $20.3 million, compared to $18.4 million in the comparable six months ended March 31, 2024.
Current report
Net other income for the six months ended March 31, 2025 was $2.8 million as compared to $4.8 million for the comparable six months ended March 31, 2024. The decrease in other income for the six-month period is also primarily related to a decrease in interest income associated with a change in market wide rates and principal balances held, as well as decrease in research and development incentive income, as a result of the completion of the open label extensions of our Australian clinical trials
Current report
Net cash used in operating activities for the six-months ended March 31, 2025 was $18.0 million, compared to $19.0 million during the comparable period ended March 31, 2024. The principal reason for this is due to changes in working capital as a result of (i) the receipt of the annual research and development incentive tax refund during the current quarter, whereas such amount was received in third quarter of fiscal 2024 and (ii) an increase in accrued liabilities related to activities associated with a large manufacturing run for ANAVEX®2-73, which work was not yet invoiced at March 31, 2025.
Current report
During the six months ended March 31, 2025, we received $1.6 million in cash from the exercise of stock options by our employees.
Current report
During the six months ended March 31, 2024, cash provided by financing activities was primarily attributable to cash received from the issuance of common shares at various market prices under the 2023 Purchase Agreement.
Current report
On March 31, 2025, there was an unused amount of $110.8 million under the 2023 Purchase Agreement. The Company will need to obtain effectiveness of a new registration statement in order to access funds under the 2023 Purchase Agreement.
Removed paragraphs (16)
Previous report
ITEM 2. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS.
Previous report
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.
Previous report
Source:
Previous report
Clinical Trials Overview
Previous report
Schizophrenia, Frontotemporal Dementia and Alzheimer’s disease
Previous report
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.
Previous report
Our Pipeline
Previous report
Compounds that have been subjects of our research include the following:
Previous report
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 model.
Previous report
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.
Previous report
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.
Previous report
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.
Previous report
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 underClinical Trials Overview – Schizophrenia, Frontotemporal Dementia and Alzheimer’s disease.
Previous report
The first of these trials, the ANAVEX®3-71-SZ-001 clinical trial, commenced in March 2024 and is more fully described above underClinical Trials Overview – Schizophrenia.
Previous report
Net cash used in operating activities for the three-months ended December 31, 2024 was $12.1 million, compared to $7.3 million during the comparable period ended December 31, 2023. The principal reason for this is an increase in net cash expenses, after taking into account non-cash share-based compensation, over the comparable period of approximately $3.7 million, as well as positive changes in other working capital accounts in the current three-month period, as compared to the comparable three-month period.
Previous report
On December 31, 2024, an amount of $110.8 million remained available under the 2023 Purchase Agreement.
Reworded paragraphs (34)
Previous wording
We have based these forward-looking statements largely on our current expectations and projections about future events, including the responses we expect from the FDA and other regulatory authorities and financial trends that we believe may affect our financial condition, results of operations, business strategy, preclinical studies and clinical trials, and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions including without limitation the risks described in “Risk Factors” in Part I, Item 1A of our Annual Report on Form 10-K filed with the Securities and Exchange Commission on December 23, 2024. These risks are not exhaustive. Other sections of this Quarterly Report on Form 10-Q include additional factors which could adversely impact our business and financial performance. Moreover, we operate in a very competitive and rapidly changing environment. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. We cannot assure you that the events and circumstances reflected in the forward-looking statements will be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable laws including the securities laws of the United States, we assume no obligation to update or supplement forward-looking statements.
Current wording
Commission on December 23, 2024. These risks are not exhaustive. Other sections of this Quarterly Report on Form 10-Q include additional factors which could adversely impact our business and financial performance. Moreover, we operate in a very competitive and rapidly changing environment. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. We cannot assure you that the events and circumstances reflected in the forward-looking statements will be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable laws including the securities laws of the United States, we assume no obligation to update or supplement forward-looking statements.
Previous wording
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.
Current wording
Anavex has a portfolio of compounds varying in sigma-1 receptor (SIGMAR1) binding activities. 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 also play a role in modulating the cellular response to viral infection and ameliorate pathogenesis.
Previous wording
Anavex has a portfolio of compounds varying in sigma-1 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.
Current wording
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.
Previous wording
Reyes S et al., Sci Rep. 2021 Aug 25; 11(1):17150
Current wording
**Source: Reyes Setal., Sci Rep. 2021 Aug 25; 11(1):17150
Previous wording
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.
Current wording
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.
Previous wording
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. 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 analyses were performed by outside consultancy companies.
Current wording
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 Australia. 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 analyses were performed by outside consultancy companies.
Previous wording
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 disease.
Current wording
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. 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 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. Throughout the scientific review process with the EMA, we may receive feedback or comments which, while not a conclusive decision, could suggest the application provided is insufficient to support the marketing authorization. We may not be able to sufficiently address these comments or requests. Alternatively, these comments or requests could lead us to decide, after consultation with our advisors or the regulatory authorities, to withdraw our MAA for blarcamesine. The Company plans to announce the results when the EMA review and decision-making is finished and does not plan to provide interim updates.
Previous wording
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.
Current wording
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.
Previous wording
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 >6-month Parkinson’s disease study.
Current wording
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.
Previous wording
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.
Current wording
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.
Previous wording
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.
Current wording
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.
Previous wording
In February 2016, we presented positive preclinical data for ANAVEX®2-73 in Rett syndrome, a rare neurodevelopmental disease. 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 that mimic Rett syndrome. The study was funded by the International Rett Syndrome Foundation (“Rettsyndrome.org”). In January 2017, we were awarded a financial grant from Rettsyndrome.org of a minimum of $0.6 million to cover some of the costs of a multicenter Phase 2 clinical trial of ANAVEX®2-73 for the treatment of Rett syndrome. This award was received in quarterly instalments which commenced during fiscal 2018.
Current wording
In February 2016, we presented positive preclinical data for ANAVEX®2-73 in Rett syndrome, a rare neurodevelopmental disease. 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 that mimic Rett syndrome. The study was funded by the International Rett Syndrome Foundation.
Previous wording
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 = 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. No other clinical trials with ANAVEX®2-73 related to Rett syndrome have been conducted in the United States.
Current wording
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. The RPD 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. At the present time, the Company does not plan to conduct a clinical trial in the United States. 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, 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 = 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.
Previous wording
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 thatexcluding 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.
Current wording
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 thatexcluding 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.
Previous wording
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.
Current wording
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 FTD.
Previous wording
The Phase 1 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.
Current wording
In July 2020, we commenced the First-in-Human Phase 1 clinical trial of ANAVEX®3-71. 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.
Previous wording
Based on these results, and ANAVEX®3-71’s pre-clinical profile, we intend 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.
Current wording
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. The first of these trials is being conducted in Schizophrenia.
Previous wording
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.
Current wording
In May 2025 we announced the completion of enrollment of Part B of the placebo-controlled Phase 2 study, which includes more participants and a longer treatment duration, and will provide more comprehensive data on the efficacy and safety of ANAVEX®3-71 in schizophrenia. We expect to report top-line data of the Phase 2 ANAVEX®3-71-SZ-001 clinical trial in the second half of 2025.
Previous wording
We hold ownership or exclusive rights to twenty-six (26) issued U.S. patents, nineteen (19) pending U.S. patent applications, and numerous PCT and ex-U.S. patent applications relating to our drug candidates, methods associated therewith, and to our research programs.
Current wording
We hold ownership or exclusive rights to twenty-seven (27) issued U.S. patents, twenty-two (22) pending U.S. patent applications, and numerous PCT and ex-U.S. patent applications relating to our drug candidates, methods associated therewith, and to our research programs.
Previous wording
Further, we own two issued U.S. patents with claims directed to methods of treating cardiac dysfunction with ANAVEX®2-73. These patents are expected to expire in July 2038, absent any patent term extension for regulatory delays. Additionally, we own two issued U.S. patents for the treatment of insomnia, anxiety, or agitation. 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. 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 2037, absent any patent term extension for regulatory delays.
Current wording
Further, we own two issued U.S. patents with claims directed to methods of treating cardiac dysfunction with ANAVEX®2-73. 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 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 delays.
Previous wording
Comparison of the three months ended December 31, 2024 and 2023
Current wording
Comparison of the three- and six- months ended March 31, 2025 and 2024
Previous wording
Total operating expenses for the three-months ended December 31, 2024 were $13.6 million, compared to $11.4 million for the comparable three-months ended December 31, 2023.
Current wording
Total operating expenses for the three months ended March 31, 2025 were $12.5 million, compared to $12.6 million for the comparable three months ended March 31, 2024. Total operating expenses for the six months ended March 31, 2025 were $26.1 million, compared to $24.0 million for the comparable six months ended March 31, 2024.
Previous wording
Our research and development expenses for the three-months ended December 31, 2024 were $10.4 million, as compared to $8.7 million for the three-months ended December 31, 2023. The increase in research and development expenses during the three-month period is primarily related to the following:
Current wording
The increase in research and development expenses during the three- and six-month periods is primarily related to the following:
Previous wording
These increases were partially offset by (i) a decrease of approximately $0.6 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 $0.6 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 open label extension.
Current wording
These increases were partially offset by (i) a decrease of approximately $0.6 million in the three-month period and $1.2 million in the six-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 open label extension and (ii) a decrease in stock based compensation charges of $0.8 million in the three-month period and $0.9 million in the six-month period due to a change in estimates associated with milestone-based options.
Previous wording
The following table summarizes our research and development expenses for the three-months ended December 31, 2024 (in thousands):
Current wording
The following table summarizes our research and development expenses for the three- and six-months ended March 31, 2025 and 2024 (in thousands):
Previous wording
During the three-months ended December 31, 2024 and 2023, external service providers cost by product candidate was as follows (in thousands):
Current wording
During the three- and six-months ended March 31, 2025 and 2024, external service provider costs by product candidate was as follows (in thousands):
Previous wording
General and administrative expenses were $3.1 million for the three months ended December 31, 2024, as compared to $2.7 million for the same quarter of fiscal 2023. The primary reason for the increase in general and administrative expenses is an increase in legal and professional fees.
Current wording
General and administrative expenses were $2.6 million for the three months ended March 31, 2025, as compared to $2.9 million for the same quarter of fiscal 2024. General and administrative expenses were $5.8 million for the six months ended March 31, 2025, as compared to $5.6 million for the six months ended March 31, 2024. In both periods, increases in legal fees were offset by a decrease in stock based compensation charges.
Previous wording
The net amount of other income for the three-months ended December 31, 2024 was $1.5 million as compared to $2.8 million for the comparable three-months ended December 31, 2023. The increase in other income is primarily related to a decrease in interest income associated with a change in market wide rates and principal balances held, as well as an increase in foreign exchange losses as a result of the fall of the Australian dollar against the US dollar during the current period.
Current wording
Net other income for the three-months ended March 31, 2025 was $1.3 million, as compared to $2.1 million for the comparable three-months ended March 31, 2024. The decrease in other income is primarily related to a decrease in interest income associated with a change in market wide rates and principal balances held, as well as decrease in research and development incentive income, as a result of the completion of the open label extensions of our Australian clinical trials.
Previous wording
Net loss for the three-months ended December 31, 2024, was $12.1 million, or $0.14 per share, as compared to $8.6 million, or $0.11 per share in the comparative quarter of fiscal 2023. The increase in net loss for the year-to-date period is primarily related to an increase in research and development expenditures and a decrease in other income, as discussed above.
Current wording
Net loss for the six-months ended March 31, 2025, was $23.3 million, or $0.27 per share, as compared to $19.2 million, or $0.23 per share for the six-months ended March 31, 2024. The increase in net loss for the quarter and year-to-date periods is primarily related to an increase in research and development expenditures and a decrease in other income, as discussed above.
Previous wording
On December 31, 2024, we had net current assets of $110.9 million, a decrease of approximately $9.3 million from our year ended September 30, 2024. The decrease in net current assets primarily relates to cash utilized in operations during the period.
Current wording
On March 31, 2025, we had net current assets of $99.8 million, a decrease of approximately $20.5 million from our year ended September 30, 2024. The decrease in net current assets primarily relates to cash utilized in operations during the period.
Previous wording
The following table summarizes cash flows during the three-months ended December 31, 2024 and 2023 (in thousands):
Current wording
The following table summarizes cash flows during the six months ended March 31, 2025 and 2024 (in thousands):
Previous wording
Cash provided by financing activities for the three-month period ended December 31, 2024 was $0.7 million, compared to $0.06 million during the comparable three-month period ended December 31, 2023. Cash provided by financing activities in both periods is primarily attributable to cash received from the exercise of stock options by our employees.
Current wording
Cash flows from financing activities for the six-month period ended March 31, 2025 was $1.6 million, compared to cash provided from financing activities of $7.3 million during the comparable six-month period ended March 31, 2024.
Previous wording
On any business day and subject to certain customary conditions, the Company may direct Lincoln Park to purchase up to 200,000 shares of Common Stock (such purchases, “Regular Purchases”). The amount of a Regular Purchase may increase under certain circumstances based on the market price of the Common Stock; provided, however, that Lincoln Park’s committed obligation under any Regular Purchase shall not exceed $4.0 million. The purchase price of shares of Common Stock will be based on the then prevailing market prices of such shares at the time of sales as described in the 2023 Purchase Agreement. There are no limits on the price per share that Lincoln Park may pay to purchase Common Stock under the 2023 Purchase Agreement. In addition, if the Company has directed Lincoln Park to purchase the full amount of Common Stock available as a Regular Purchase on a given day, it may direct Lincoln Park to purchase additional amounts as “accelerated purchases” and “additional accelerated purchases,” each as set forth in the 2023 Purchase Agreement.
Current wording
On any business day and subject to having an effective registration statement and subject to certain customary conditions, the Company may direct Lincoln Park to purchase up to 200,000 shares of Common Stock (such purchases, “Regular Purchases”). The amount of a Regular Purchase may increase under certain circumstances based on the market price of the Common Stock; provided, however, that Lincoln Park’s committed obligation under any Regular Purchase shall not exceed $4.0 million. The purchase price of shares of Common Stock will be based on the then prevailing market prices of such shares at the time of sales as described in the 2023 Purchase Agreement. There are no limits on the price per share that Lincoln Park may pay to purchase Common Stock under the 2023 Purchase Agreement. In addition, if the Company has directed Lincoln Park to purchase the full amount of Common Stock available as a Regular Purchase on a given day, it may direct Lincoln Park to purchase additional amounts as “accelerated purchases” and “additional accelerated purchases,” each as set forth in the 2023 Purchase Agreement.
Previous wording
During the three-months ended December 31, 2024 and 2023, the Company did not issue any shares of common stock under the 2023 Purchase Agreement.
Current wording
During the six-months ended March 31, 2025, the Company did not issue any shares of common stock under the 2023 Purchase Agreement. 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.
Rearranged current paragraphs (2)
Current report — wording carried from elsewhere
We have based these forward-looking statements largely on our current expectations and projections about future events, including the responses we expect from the FDA and other regulatory authorities and financial trends that we believe may affect our financial condition, results of operations, business strategy, preclinical studies and clinical trials, and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions including without limitation the risks described in “Risk Factors” in Part I, Item 1A of our Annual Report on Form 10-K filed with the Securities and Exchange
Current report — wording carried from elsewhere
Net loss for the three-months ended March 31, 2025, was $11.2 million, or $0.13 per share, as compared to $10.5 million, or $0.13 per share in the comparative quarter of fiscal 2024.
Rearranged previous paragraphs (6)
Previous report — wording carried elsewhere
In March 2019, we commenced the first Phase 2 clinical trial in a Rett syndrome program of ANAVEX®2-73 for the treatment of Rett syndrome. The clinical trials were conducted in a range of patient age demographics and geographic regions, utilizing an oral liquid once-daily formulation of ANAVEX®2-73.
Previous report — wording carried elsewhere
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.
Previous report — wording carried elsewhere
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.
Previous report — wording carried elsewhere
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.
Previous report — wording carried elsewhere
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.
Previous report — wording carried elsewhere
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.