AVXL

Good morning, everyone. And welcome to the Anavex Life Sciences Corp. fiscal 2026 first quarter conference call. My name is Clint Tomlinson. I will be your host for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. During the session, if you would like to ask a question, please use the Q&A box or raise your hand. Please note this conference is being recorded, and the call will be available on Anavex's website at www.anavex.com. With us today is Dr. Christopher Missling, President and Chief Executive Officer, and Sandra Boenisch, Principal Financial Officer. Before we begin, please note that during this conference call, the company will make some projections and forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. We encourage you to review the company's filings with the SEC, including, without limitation, the company's forms 10-K and 10-Q, to identify the specific factors that may cause actual results or events to differ materially from those described in these forward-looking statements. These factors may include, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, the need and ability to obtain future capital, and maintenance of intellectual property rights. This conference call discusses investigational uses of agents in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such products will successfully complete clinical development or gain health authority approval. And with that, I would like to turn the call over to Dr. Missling.

Thank you, Clint, and good morning, everyone. Thank you for being with us today to review our first quarter financial results and quarterly business update. As we enter 2026, we continue to progress our innovative clinical pipeline with a particular focus on our lead candidate, oral blarcamesine, in early Alzheimer's disease. Based on our commitment to improving the lives of patients with neurological disorders, we remain excited about the therapeutic potential of oral blarcamesine. We look forward to working with the regulatory agencies in Europe and in the US to advance blarcamesine as a potential new treatment option for patients. We recently announced Anavex's participation as a key industry partner in Access AD, a major new European initiative designed to accelerate the adoption of innovative diagnostic and therapeutic approaches for Alzheimer's disease across real-world clinical settings. The multiyear program is funded by the European Commission's Innovative Health Initiative and unites leading academic centers, technology developers, industry innovators, and patient organizations to strengthen equitable access to timely and effective Alzheimer's disease care. As part of the consortium, blarcamesine will be evaluated in a clinical prediction study. As an update to our regulatory pathway, in January, we announced feedback from an FDA Type C meeting in which the FDA shared their feedback on Anavex's development plans. The meeting discussed the potential pathways to support blarcamesine for Alzheimer's disease. In order to move forward, it is expected that existing data from the Phase 2b/3 Anavex 2-73 AD-004 program be submitted to the FDA. In December, as expected, the CHMP adopted a negative opinion on the marketing authorization application for blarcamesine. Subsequently, on December 18, Anavex announced it had requested the EMA to reexamine its opinion. We are working closely with the EMA during this process, which is being led by a different rapporteur and co-rapporteur. In November, we announced presentations at the 18th CTAD conference in San Diego. The oral late-breaking communication on oral blarcamesine Phase 2b/3 trial confirms identified precision medicine patient population, significant broad clinical and quality of life improvements for early Alzheimer's disease patients, and two poster presentations featuring blarcamesine. Looking forward, we will provide both regulatory and clinical trial updates on blarcamesine in other indications such as Parkinson's disease and fragile X. This will include disclosure of planned future clinical trial designs as we continue to advance our therapeutic pipeline. Additionally, new scientific findings will be presented at upcoming conferences or in upcoming publications. An oral presentation at the 16th Intrinsic Capacity Frailty and Sarcopenia Research Conference for Healthy Longevity to be held March 12 at Johns Hopkins University Bloomberg Center in Washington DC. The new findings on a clinical relationship with a biomarker correlation between clinical endpoints and reduced brain region atrophy with blarcamesine in early Alzheimer's disease. A publication on Alzheimer's disease regarding precision medicine AB-clear populations of the Anavex 2-73 AD-004 Phase 2b/3 trial. Another publication on Alzheimer's disease on the precision medicine gene, collagen 24A1, which with an estimated over 70% prevalence in the early Alzheimer's disease population, has the potential to establish effective treatment of early Alzheimer's disease through the effectiveness of autophagy-enhancing blarcamesine. And a publication regarding fragile X, blarcamesine corrects EEG biomarkers of cortical dysfunction in a mouse model of fragile X syndrome. With regard to Anavex 3-71, we will be advancing Anavex 3-71 towards pivotal clinical studies for the treatment of schizophrenia-related disorders. And now I would like to direct the call to Sandra Boenisch, Principal Financial Officer of Anavex, for a financial summary of the recently reported quarter.

Thanks, Christopher. Good morning to everyone. I am pleased to share with you today our first quarter financial results. Our cash position at December 31 was $131.7 million with no debt. During the quarter, we utilized cash and cash equivalents of $7.1 million in operating activities after taking into account changes in non-cash working capital accounts. As of today, we anticipate that at the current cash utilization rate, our cash runway is more than three years. Our research and development expenses for the quarter were $4.7 million as compared to $10.4 million for the comparable quarter of last year. General and administrative expenses were $2.1 million as compared to $3.1 million for the comparable quarter of last year. And compared to the same quarter of fiscal 2025, we saw a decrease in operating expenses, mostly driven by the completion of a large manufacturing campaign of blarcamesine conducted in fiscal 2025, and a decrease in clinical trial activities as a result of the completion of our Anavex 3-71 Phase II study in schizophrenia. And lastly, we reported a net loss of $5.7 million for the quarter or $0.06 per share. Thanks, and I will turn it back to you, Christopher.

Thank you, Sandra. In summary, we are focused on continuing to advance the development of our precision medicine compounds and are excited to be potentially making a difference to individuals suffering from neurological diseases by presenting scalable treatment options alongside the ease of oral administration. I would now like to turn the call back to Clint for Q&A.

Thank you, Christopher. We will now begin the Q&A session. If you have a question, please raise your hand or enter it in the Q&A box. And our first question will come from Ram Selvajara from HC Wainwright. You should be connected now, Ram. But I see you muted. Hello? Can you hear me?

Yes. Thanks so much for taking our questions. Firstly, I was wondering if you could, at this juncture, provide us with some additional information regarding who the rapporteur and co-rapporteur are for the reexamination of the CHMP opinion on blarcamesine.

The 27 countries of the EU decide on two rapporteurs. One of the two countries of the 27 will be rapporteurs.

Okay. Can you provide us with additional information regarding the timeline with which the reexamination is likely to occur? My understanding is that, in effect, it starts a new clock, but that this might be as short as six months. Can you confirm that?

That is correct. It is a sixty plus sixty day period where we respond to the reexamination request. And then the review by the two rapporteurs will take another sixty days. So that's why we stated that we expect this process to last for the first half of this year. Can you provide a timeline regarding when you anticipate potentially filing a formal NDA submission with the FDA? This is a plan we will advance once we are getting closer. But the last meeting was very productive we had with the FDA. And so we continue with this request, which we were given that we will provide the full data package to the FDA for addressing their review and expecting next steps from there.

Can you just remind us what type of meeting this was that you held with the FDA, the most recent one?

That was a Type C meeting.

Okay. Thank you.

Thank you, Ram. Next question comes from Tom Bishop of BI Research. Tom, you should be on now.

Ring. Can you hear me?

Yes. Go ahead.

Can you go into a little bit more detail about what additional information will be in the resubmission to the EMA in terms of will ABC clear data be in there, varying volume data, follow 24A1, and OLE. Can you just give us a little bit more meat on the bone?

That's absolutely possible. So for background, in the resubmission, we are able to address and provide feedback on the arguments why this drug should be reexamined for approval for EMA review. And as a reminder, there is a requirement for granting conditional approval if the disease is serious, if there's a major unmet need, if the data shows clinically meaningful effects, if there's a strong mechanistic rationale especially linking genetic variants, and if the supporting evidence from translational data is available and the sponsor is then also committing to a study in executing it and confirming the efficacy during the approval process. And we are including the data of the AD-004 study, the open-label study, the data on the AB-clear study population, as well as the correlation of the efficacy of the clinical efficacy with the brain atrophy reduction.

Now was none of that actually in the, you know, those last few that you mentioned in the original submission such that this could potentially be more persuasive as it is for me.

Yeah. It's really like a process, I would say, and we also understand that is something which a counterparty has to digest. And maybe that is the reason also we've seen now in the past several cases where even with drugs which were prior approved already, and with very large companies submitting those, you know, trial data, well, ended up at the same situation where we ended up today as well. But, we can, of course, not guarantee the approval in this reexamination procedure. But it seems to be a question of how to repackage or rearticulate the strength of the package or of the data.

Okay. And with the FDA, I know the question was asked when might you file this data with the FDA. I mean, it kinda already exists, so I'm was just wondering if you can be any more clear about why we can't they can't why you can't get that data to the FDA very soon?

It's in process, and you have to also understand the FDA has a certain meeting request which requires some time to schedule. And this is in the process as well. So that's why it's not like you just ship something over, and then you get feedback you have to make it in consistency with a meeting request. And that's what will happen.

Okay. Are there any correct me if I'm getting the scene out here, but are there any trials currently in progress? The only trial we have ongoing is right now the compassionate use program for Rett syndrome. In three countries, in three continents. In Canada, in the UK, in Australia, and we have also the compassionate use ongoing for Alzheimer's disease. So we are planning now the studies in Parkinson's disease, in fragile X, and another indication which is not disclosed yet, and we also will proceed with the Alzheimer trial which we I mentioned before.

Okay. Well, is the it's been a little while since the Rett trial finished, the Parkinson's trial was finished several years now, and I'm just wondering if you can give us any near-term timeline for first trial. Some of these schizophrenia, just wrapped up that.

Yeah.

As to when something we'll we'll we'll get something in this clinic. Yeah. Yep. Absolutely good question. We also plan a schizophrenia program to continue. As I mentioned this morning, so we are really gonna be very busy with trials, and we are very excited about it. And just to let you know, the Parkinson's disease trial has not been started yet. It was Parkinson's disease dementia. But it's the basis of which we are executing the Parkinson's disease trial.

Okay. I guess that's it for me for now. Thank you.

Thank you, Tom. The next question will come from Jesse Silveira from Spirit of the Coast Analytics. You can go ahead, Jesse. Hear me alright?

Yes. Thank you. Hi. Good morning. This is Jesse Silveira with Spirit of the Coast Analytics. Thank you for taking my questions today. Before we get into some of my, I guess, more elaborate questions, maybe we can start with some quicker pitches. First up, something a lot of people have been kind of scratching their heads on is clarity for CHMP rejection, in particular, we know that blarcamesine works better for patients with sigma-1 wild type. As a part of the CHMP rejection, the agency stated, and I quote, the main study failed to demonstrate effectiveness and safety of blarcamesine Anavex, in patients with early Alzheimer's disease who do not have a mutation in the sigma-1 gene, end quote. So this statement appears contrary to the facts because the drug is effective for patients, who do not have a mutation in the sigma-1 gene, also known as sigma-1 wild type. So is it the company's opinion that the CHMP made an error in how they phrased their rejection, or can you clarify the company's understanding of this statement in particular?

Yeah. We would not criticize the regulatory bodies, but we would say that in consistency with our interpretation of the trial, we met the ADAS-cog 13 and there was more significant in the wild type sigma-1 population as well as in the from the boxes which also was superior to the ITT in the wild type compared to the ITT population. The ADL ADCS ADL endpoint, was the only one which was not significant, although it was trending positively. And as we and the academic world found out that this scale is not sensitive enough to pick up the changes of activities of the living in forty-eight weeks in an early Alzheimer's population. So that is the maybe the only difference in interpretation of the trial. That that was, maybe differently evaluated. But now when you go to the AB-clear population, you will see, and we submitted that for publication. It's already publicly available a preprint that the AB-clear population, which includes sigma-1 wild type, carriers with the collagen 24A1 wild type, gene that those patients have significance reached significance across the board. So for ADAS-cog 13, for ADCS ADL, and for CDR Sum of the Boxes. And they're not only achieving significance, but they're also achieved this with highly clinically meaningful effect sizes, which are sometimes two to three times larger than, what we have seen so far from other compounds. In the pipeline or on the market. So that's kind of, like, why this is intriguing now to also point that out and and have that discussion put that forward.

Okay. Thank you for that. And I'm gonna have I'm gonna skip around a minute just because you kind of led into it. So stated in your Borrow Capital interview with Jason a few weeks ago that the reexamination would be under a CMA path and not a full market authorization. And in the interview, you explained that ADCS ADL one of your co-primary endpoints had been invalidated as a reliable measure during your trial analysis phase due to a lack of sensitivity found within the community despite its previous status as the gold standard in Alzheimer's trials. You then went into detail about new statistical methodology that the company was looking to use featuring a higher p-value threshold of 0.0167. And I know that the company has met ADAS-cog 13 and CDR Sum of the Boxes across all genetic cohorts with this p-value or better. So the question is, does using this new threshold allow the company to circumnavigate the ADCS ADL miss, and will regulators in your view, accept the scientific invalidation of ADCS ADL combined with your new gatekeeping strategy? If you can give any on that.

Yeah. As I just stated, this is exactly the discussion which is probably ongoing if this ADL is 4. And if you follow science, you would agree with that. Because it's an endpoint which has been earmarked as being useful for overt Alzheimer, for moderate and severe Alzheimer, but not sensitive enough for the early Alzheimer population. And that was confirmed actually in guidances from the regulatory bodies. So you would assume that that is a fair argument to have, and, we stated that argument and to make that argument as well.

Okay. Thank you for that. And, with that said, you went over the sixty plus sixty day timeline earlier for this reevaluation. We should be, I believe, near sixty days now. Have you already submitted the new strategy and package to CHMP and has a SAG been appointed yet?

We will update everybody once we have the result of this process. We will not comment on the ongoing process. But the SEC will be part of the review process since we requested that, and we will expect this to be given to us a dialogue involving the SAG, the Scientific Advisory Group from the EMA for from the neurology team.

Okay. Thank you. And if I have it correct, you have committed to running a confirmatory phase four trial if approved for CMA using paying patients as a real-world cohort. Isn't is that correct?

Sorry. What patients?

Like, paying patients in the EU. So assuming you are actually approved under CMA, will you be running a phase four trial with these patients? We will. Or how would that look, I guess?

Yeah. We would run a trial as the regulatory body the CHM guidelines, provides for. That you get approved, and then in parallel, you will run a confirmatory study. Yes.

Okay. And I think relevant to additional Alzheimer's trials, is on January 28th of this year, Alzheimer Europe launched the prevalence of dementia in Europe 2025 report which projected a 64% surge in dementia across Europe by 2050. Based on our research, it appears that Europe is not on course to meet projected health strategies, especially those centered on dementia. And it looks like they're kind of, as a as the EU, moving away from social work and dimension favor of defense and economy. In light of these statements, it's our understanding that Anavex is set to participate in Access AD, funded by the European Commission. Can you please give more detail on how blarcamesine, a currently unapproved drug, is to be involved in this program? Like, is the company running this trial? Are endpoints and objectives of this trial? When will the first patient be dosed, or anything else you'd like to offer.

The Access AD program is really a great opportunity for acknowledging Anavex as a participant and being part of the ecosystem in Europe for Alzheimer's disease, which involves both academic institutions as well as government entities and advocacy groups within Europe. So we're very pleased and excited about being part of that. A specific carve-out or not carve-out, especially part of this very large grant, if you like, is a dedicated clinical trial of blarcamesine as a placebo-controlled trial to look for data of prediction of the effect of blarcamesine in Alzheimer patients, in early Alzheimer patients, and that involves, review of biomarkers, and novel biomarkers, looking at autophagy signals, and, also including efficacy. And we're planning to use this trial also for a regulatory, specific, goal. So we will make this trial part of our package for confirming the efficacy of blarcamesine in early Alzheimer's disease. So it's a very intriguing project to be part of. And the Access AD program consists of multiple features. Among them is also a review of healthy diet. Also, a supplement diet is part of that. And, they're all separate. They're not together. And as I just mentioned, one part is explicitly a trial of blarcamesine. In our placebo-controlled clinical trial.

I'm sorry if you mentioned is this an early Alzheimer's patients, or is this is there, like, a preventative component to this trial?

Yeah. So it's a good question. It could end up being a preventative also, but right now, it's consistent with an early Alzheimer's population as a target population.

Okay. And this would be considered AD-006 on your pipeline chart. Is that correct?

That's correct. Yes.

Okay. AD-006. Okay. Great. And I think I'm finishing up here. Is the atrophy to clinical improvement analysis or paper complete? And maybe if you could give any expectations on when we could get eyes on that.

The yeah. So we have submitted now three papers. We I mentioned this morning. And the atrophy paper is still not submitted, but will be submitted soon as well.

Okay. Great. And okay. That's pretty much all I have. Kudos on your JPM presentation and the new website format. They look great. And it's striking how little to lose I think, the CHMP has by granting a CMA considerably considering this, you know, the soundly claimed safety and efficacy the drug on cognition, objective brain atrophy markers, not to mention patient-assessed improvements. Measured by the quality of life AD survey. So we have no further questions, and thank you again for having us.

We appreciate that. Thank you.

Thank you, Jesse.

Doctor Missling, we have no more questions at this time.

Thank you. So in closing, we continue to focus on execution as we advance our therapeutic pipeline to potentially improve patients' lives living with these devastating conditions. We are energized by the possibility of making a meaningful impact for people living with neurological diseases offering treatment options that are not only scalable, but also far easier to administer through an oral route. By lowering barriers to access and simplifying delivery, we hope to bring innovative therapies to a broader population and improve quality of life in a tangible way. Thank you.

Thank you, ladies and gentlemen, for participating in the call today. We appreciate it. And this will conclude the conference. You may now disconnect.

Good morning, everyone, and welcome to the Anavex Life Sciences Fiscal 2025 Fourth Quarter Conference Call. My name is Clint Tomlinson, and I'll be your host for today's call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session. And during this session, you would like to ask a question, please use the q and a box or raise your hand. Please note that this conference is being recorded, and the call will be available for replay on website at www.anavex.com. With us today is doctor Christopher Missling, president and chief executive officer and Sandra Bohnish, financial officer. Before we begin, please note that during this conference call, the company will make some projections and forward looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. We encourage you to review the company's filings with the SEC that include, without limitation, the company's forms 10 k and 10 q, which identify the specific factors that may cause actual results or events to differ materially from those described in these forward looking statements. These factors may include, without limitation, risks inherent in the development and or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need an ability to obtain future capital, and maintenance of intellectual property rights. This conference call discusses investigational uses of agents in development and is not intended to convey conclusions about efficacy or safety. And there is no guarantee that any investigational uses of such products will successfully complete clinical development or gain health authority approval. And with that, I would like to turn the call over to doctor Misslin.

Thank you, Clint. And good morning, everyone. Thank you for being with us today to review our Q4 financial results and quarterly business update. We are fully committed to bringing Oral Black Amazin and oral ANAVEX three seventy one to patients. We are dedicated to delivering on the value of our pipeline and maximizing its potential for patients investors, and our employees. Over the coming months, we will continue to focus on progressing our clinical trials and regulatory actions. At the same time, we're aiming to expanding our collaborative initiatives and strategic partnership activities. As previously announced, through our update on the status of the regulatory filing of blacaramazine in Europe, we expect the CHMP to adopt a negative opinion on the MAA at its December meeting. We intend to request a reexamination of the CHMP opinion upon its formal adoption based on feedback and continued guidance from the CHMP, EMA and the Alzheimer disease community. DMA procedures adopted by the CHMP allow an applicant to request reexamination of its decision. Which would be undertaken by a different set of reviewers that conduct a new examination. Independent from the first opinion. Our expert advisers investigators, as well as patients and their caregivers encourage us our commitment to continue working in partnership with global regulatory bodies to advance science and potentially new treatment options for patients and their families. As part of the MAA review process, we have successfully undergone a full good clinical practice GCP inspection of the trial data by EMA. The manufacturing package has passed the EMA review as well. A good clinical practice GCP inspection is an official review by a regulatory authority over clinical trials documents facilities, records, and other resources to ensure compliance with g p GCP guidelines. We're looking forward to working closely with EMA and other stakeholders advance our investigational therapy for early Alzheimer disease. Importantly, we also announced we had initial contacts with the authorities in The US regarding our Alzheimer's disease program. And we intend to provide further updates on our interaction with the FDA as they become available. Going forward, we will provide both regulatory and clinical trial updates on dacamazine in other indications, such as Parkinson disease, Rett syndrome, and fragile X. This will include the disclosure of planned future clinical trial designs as we continue to advance our therapeutic pipeline. Scientific & Clinical Data Updates

During the most recent quarter, we announced several new scientific and medical publications includes a peer reviewed publication in the journal Neuroscience Letters, titled Prevention of Memory Impairment: in Hippocampal Injury with blacamazine in an Alzheimer's disease model. This study shows that pretreatment with blacarbazine prevented amyloid beta induced memory impairment. And brain oxidative injury suggesting that blackamcin is an attractive candidate for Alzheimer disease pharmacological prevention. A peer reviewed publication the journal Eye Science asserting the precise autophagy mechanism of sigma one receptor through blacamazine activation titled conserved LI R specific interaction of sigma one receptor in GABA RAB. A publication oral glycogen phase two b slash three trial confirms identified precision medicine patient population significant broad clinical and quality of life improvements for early Alzheimer disease patients. To be available online as a preprint and in submission to a peer reviewed medical journal. Anavex announced the latest published scientific results for blacamazine. On all standard scales for measuring Alzheimer's disease and cognitive decline after forty eight weeks, the defined precision medicine population ABCEAR three, consisting of early Alzheimer's disease patients with confirmed and progressed pathology taking thirty milligram once daily oral blacamazine demonstrated barely detectable decline This was comparable to minimally perceptible decline in prodromal which is pre dementia aging with adults. On October 29, we announced additional long term clinical data for blacamycin, This new data demonstrated continued long term benefit from oral blacamazine compared to decline observed in the Alzheimer disease neuroimaging initiative control group also called ADNI, a control group established by a clinical research project launched by NIH in 2004. In the intent to treat population, significantly less cognitive decline was observed for the black carnosine participants compared to the acne control group at forty eight weeks with a significant and clinically meaningful difference in mean change from baseline at a 13 total score of minus 2.68. Points. Over the course of the open label extension study, at time point ninety six weeks, these two groups further diverged sharply with statistical significant differences in mean change in ADAS cogs. 13 total score at ninety six weeks of minus 6.41 points. The difference between groups continues to increase at one hundred and forty four weeks. To ADA's COC 13 total score difference of minus 12.78 points. The results provide evidence of the significant beneficial therapeutic effect of blacamazine which positively separates from black from which positively separates from the ADNI control group with duration of treatment. This significant beneficial therapeutic effect of blacamazine compared to decline observed in the ADNI control group, trans translates into seventeen point eight months of time saved with oral blacamazine. Allowing for longer independence of the patients by approximately over one point five years. Looking ahead, Annavec will be presenting additional data and scientific findings at upcoming conferences and in publications. These include the direct relationship between cognitive function and reduced brain region atrophy with blacamazine. Oral blacamazine for early symptomatic Alzheimer's robust effect size through precision medicine an analysis of the ANAVEX two seventy three AD024 randomized trial. Also, newly identified precision medicine gene collagen 24A1, with over seventy percent, seven zero, prevalence, establishes effective treatment of early Alzheimer's disease with glacamazine. And also, continued long term benefit from oral blacamazine compared to delayed start analysis and decline compared to natural history studies. ANAVEX 3-71 (Schizophrenia & Neuropsychiatry)

With regard to ANAVEX three seventy one, in October, ANAVEX announced positive top line results from its placebo controlled Phase two clinical study, evaluating ANAVEX three seventy one for the treatment of schizophrenia in adults on stable antipsychotic medication. The study successfully achieved its primary endpoint demonstrating that ANAVEX three seventy one was safe and well tolerated. The safety profile was consistent with previous studies of ANAVEX three seventy one in healthy volunteers. With no serious or severe treatment emergent adverse events reported in either Part A or part b of the study. In addition, to meeting the primary safety endpoint, secondary and exploratory analysis revealed encouraging trends in several outcome measures. Our other oral medicine candidate ANAVEX three seventy one, represents therefore, a transformative opportunity in neuropsychiatric drug development. Leveraging its unique dual sigma-one agonist unique sigma-one m one PAM mechanism to address multiple high value indications through a unified neuroinflammatory biomarker platform Further detailed analysis of randomized, strictly double blind, and placebo controlled clinical trial under DEX371 SZ001 revealed very encouraging data in suffering from schizophrenia. Following successful Phase two results from the SZ 001 study while confirming the accident safety profile of ANAVEX three seventy one, the study demonstrated reduction in GFab NYLK40 neuroinflammatory markers. G Fab is a structural protein of astrocytes in the brain, represents aberrant activation of astrocytes the major brain glycol cell lineage. Astrocytes participate in brain neural function in multiple ways. Amongst them, critical modulation of synaptic relay between neurons in neural circuits. Its dysfunction a key pathogenesis mechanism in schizophrenia. This positions ANAVEX three seventy one to advance into pivotal trials with the once daily modified release oral tablet enabling once daily dosing across depression, and psychosis indications where current therapies have failed or shown limited efficacy. Addition to schizophrenia, one high unmet need opportunity would be depression in Alzheimer's disease. With currently no approved therapies. Up to forty percent of people with Alzheimer experience significant especially in early and middle stages of the disease. Depression in Alzheimer's is associated with worse quality of life. Accelerated cognitive decline, and earlier onset of dementia symptoms. The neuroinflammatory biomarker strategy positions Anavex 371 to potentially achieve disease modification claims beyond symptomatic treatment, representing a paradigm shift in neuropsychiatric drug development. And now I would like to direct the call to Sandra Boenisch, principal financial officer of ANAVEX, for a financial summary of the recently reported quarter.

Thank an you, Christopher, and good morning to everyone here. I'm pleased to share with you today our fourth quarter financial results for our 2025 fiscal year. Our cash position as September 30 was 102,600,000.0, and we had no debt. During the quarter, we utilized cash and cash equivalents of 8,600,000.0 in our operating activities. After taking into account changes in non cash working capital accounts. As of today, with a current cash balance of over a 120,000,000 we anticipate that at the current cash utilization rate, our cash runway is more than three years. Our research and development expenses for the quarter 7,300,000.0 as compared to 11,600,000.0 in the comparable quarter of last year. General and administrative expenses were 3,500,000.0 as compared to 2,700,000.0 for the comparable quarter of last year. Compared to the same quarter of fiscal twenty twenty four, we saw a decrease in operating expenses mostly driven by the completion of a large manufacturing campaign of larcamesine and a decrease in clinical trial activities. As a result of the completion of our open label extension studies and our ANAVEX three seventy one phase two study in schizophrenia. And lastly, we reported a net loss of $9,800,000 for the quarter which is $0.11 per share. Thank you. And now I will turn the call back to Christopher.

Thank you, Sandra. In summary, we are focused on continuing to advance our precision medicine compounds we are excited to be potentially making a difference for individuals suffering from these diseases by presenting a scalable treatment alternative alongside the ease of all administration. I would now like to turn the call back to Clint for Q and A.

Thank you, Kasr. We'll now begin the Q and A session. If you have a question, please raise your hand or enter it into the q and a box. It looks like our first question will from Michael Obadiah from HC Wainwright. Hello. Good morning. So are we asking the questions on behalf of Ram Selvaraju? From H. Wainwright? Have a couple of questions for the management. And the first question is, what is the likely commercial impact of the failure of semaglutide on the outlook for glycogenesine in Alzheimer's disease? Second one is when is the next formal discussion of black hemisinin scheduled to take place with the FDA? And the third question is, what initiatives does INOVIX plan near term pursue glycemic sign approval in regions beyond the European Union and The United States? Thank you.

I appreciate the questions. So to answer the first question about the impact of the semaglutide glutide results. We understand there's an unmet medical need here. And this is certainly further highlighted by the recent setback by the two EVOQUE studies from Novo Nordisk. And also by other companies, including other large pharma companies recently, with also with anti tau injectables. So there's a lack of upcoming pipeline certainly. We also understand that the Evoque semaglutide GLP one finding highlight the complexity of Alzheimer disease biology. And the challenges of expecting metabolic pathway alone to meaningfully alter your dinner processes. But Alzheimer's more complex, involves impaired proteostasis, autophagy dysfunction, synaptic failure in multiple converging mechanism. So therapeutic effects seen in related conditions do not always translate into kind of benefit here. However, we have with oral once daily blacamazine with this upstream mechanism of action, which restores autophagy, which precedes these pathologies adjust summarized and has demonstrated in early Alzheimer disease patients clinically meaningful efficacy of slowing cognitive decline significant amounts. Some cases over fifty percent. With an acceptable safety profile with no ARIA, and as demonstrated in the phase two b less free study. So the answer to the question is this makes it more clear that this is a complex disease and there's a lack of compounds near term available for patient to address this unmet need. Second question is about timing. So we provide as we stated, updates what we'll follow-up in the initial discussion with The US regulators and we'll provide updates as we receive them. But we're very excited about the initiation of these discussions. Regarding the third questions, we are continuing to now explore other regulatory geographies. As well as moving forward where we can see fit to address open questions. So I trust this addresses the question.

Yes. Very much for the clarity and transparency.

Thank you.

The next question is gonna come from Tom Bishop at BI Research. Tom, you need to unmute

per the press release, the, CHMP seems to have given you some guidance about the additional information they they need to see, for example, biomarker. But can you elaborate, what this includes?

So we we want to proceed with the reexamination. Because we owe it to the patient, and we get the feedback also from investigators that the unmet need is very high, And we it boils down to CHMP the benefit await the risks. Of the drug to be on the market. And that discussion includes all available data. And it might be you know, to make the glass half full, that the should or may out biomarker, which are not subject to influence, might be helping in getting to that point. So that is the background of biomarker best including biomarker assessments.

Well, there was no particular biomarkers that you you hope to bring out?

We have communicated, and it's, been published that we have a brace strong biomarker of the pathology. Which is the analogy of oncology where tumor grows and you look at the size of the tumor, which is measurable objectively, can be measured objectively, and it cannot be influenced by a patient or by anybody else. The same as in Alzheimer's disease is the brain shrinks. So the brain gets smaller, then the the brain mass shrinks, and we can measure that as well. And it's a very objective marker of neurodegeneration, and we demonstrated that this marker of neurodegeneration is significant, the less or even halted in some patients, with active oral blacamazine. While in the placebo arm, this shrink, the brain continues. Which is the clear definition of the advancement of the Alzheimer pathology. And we like to include, of course, that as well in the discussion.

What about the ABC Clear data? I mean, that was very compelling with forty eight to eighty six percent slowing depending on the gene biomarker, or combination Was this guess this was not considered by the CHPT as it came out, MP because it came out kinda late. But, can this be included for consideration on reexamination?

It's a good question. So we like to emphasize our focus is on each individual patient affected by Alzheimer. And we see that very clear beneficial signal of cognitive also clinically meaningful effect in both cognitive and functional also in all the other endpoints consistent improvement and significant improvement of the clinical outcomes that is the CGI that is the quality of life and PRQ, MMSE, all the measures are the SCOC 13, see there from the boxes, ADCS ADL, In all this a b clear, two and three, populations, we see clearly clinically meaningful and significant improvement. So we would like to also point that out and that is really good a good dataset to have and to put this forward. And also, last but not least, making the point about the focus on each individual patient we see a reversal of the negative trajectory of quality of life of the patients in seventy percent of the patients seven zero, in the trial. That means the quality of life is better after one year than at the start of the trial. That's very impactful because that's what is really impacts the individual patient.

Okay. If the approval ultimately came from the EMA, and and let's assume perhaps it was conditional. Is is there a rule of thumb or how long you would have to to do a conditional trial?

It's really not it's it's really hard to speculate about this. But we would like to make sure we wanna point out we are motivated and driven by the fact that there's a huge significant unmet need for a drug which with these features today, and we pointed out the recent pipeline failures, And also, I wanna point out that between twenty and twenty five, this year and 2030, there will be more than 300,000,000,000 of large pharma revenue at risk from loss of exclusivity with over 40% of top pharma sales exposed creating an estimated $90,000,000,000 growth gap even after internal pipeline contributions. So that means there's also a huge unmet need not only for this indication, but also for overall pipeline to be filled by large pharma.

Well, that's interesting that you brought that up because I wanted to ask about how you're coming with you know, exploring your options if you get approval. For example, blarcamesine to market. large pharma, organizations, and so forth to take

Yes. So we pointed out in just in this call that one of the key things we are focusing on now is expanding the corporate development partnership activities And we mentioned that we are presenting at the most important conference every year, which takes place in San Francisco in early January. And we are a presenting company on Wednesday. On at that conference itself. And that allows for more meaningful discussions, which is the hotspot for business development activities. At at this conference, and we will make sure we are present in that regard.

Okay. Well, I think it'd be a real tragedy for Alzheimer's patients to to to not see this drug approved because especially the ABC CLEAR data to me is so convincing. That and and the risks are so low, and it's oral. That it I I just can't fathom that it wouldn't get approved, but that's just me. I wish I had a vote.

We would agree. Thank you for your vote as well.

Tom, are you there?

Yeah. Okay. As long as I'm still on, is there a mechanism of action for call 241?

Yes. There is. And this will be now published in a peer review paper But in summary, I can say that collagen twenty four zero one is the ingredient key ingredient of the extracellular matrix called ACM. When you look at pictures of brain neurons or astrocytes, we see this very nice you know, connections or network like a web. Spider web description or pictures. And in the background, it's always like pitch black. And you're wondering this is how the brain looks like. And, of course, it doesn't it does not. And this background is actually the axosodular matrix. And that's where these neurons and astrocytes are residing or sitting on. Your brain. And if you have a mutation of this extracellular matrix, then your response to blacamazine is impaired. The autophagy flux the autophagy restoration, which is the recycling mechanism of the neurons, which precedes a beta and tau. So it's further upstream closer to the origination of the pathology of Alzheimer, if you like, that is impaired. And for that reason, we found that patients with a wild type, with not mutated collagen genes, they respond extremely well. And we see effects of in ADAS-Cog13, minus 4.7. In the patients with that effect. With that wild type gene. And in in the CDS or the boxes, the scores go up, up to 1.4, minus 1.4. And these are really very unprecedented effects of benefit. And we pointed out that that means since patients are actually almost not declining or declining less than prodromal patients. Which are less impaired. So that's quite impactful. And this is really intriguing science. And it will be published in a major peer review paper very soon. So extremely intriguing. And also consistent with the mechanism of blackamazin.

Great. Okay. Well well, that's it for me. I'm just excited to see this ABC data get examined by the e CHMP as well.

Appreciate it. Thank you.

Thank you for the questions, Tom. The next question going to come from Jesse Silvera. Spirit of the Coast Analytics.

Hey. Good morning. Can you hear me alright?

Yes. You're fine. Ahead, Jesse.

Good morning, Clint and doctor Missling. This is Jesse Silvera from Spirit of Coast Analytics. Thank you for taking my call. Some of these questions you've kind of addressed a little bit earlier, but hopefully you can maybe provide some additional color on on some of them. Yeah. Just to reiterate kind of one of your previous points. My first question is sort of an assumption, though I think you got at it earlier. But considering the CHMP review is ongoing and a final decision hasn't even been rendered yet, is it safe to say that you can't discuss the reasons negative CHMP trending or give details on the strategy going into the reevaluation

That that's, yeah, correct. That's correct.

Okay. Got that. And perhaps adjacent to that conversation, you think you can give more detail on a statement that was found in the fourteen November press release? It stated, quote, the company intends to request a reexamination of the CHMP opinion upon its formal adoption, including providing relevant biomarker data based on feedback and continued guidance from the CHMP, EMA, and Alzheimer's disease I think it was Tom that was getting at this earlier, but can you can you comment any further on the the biomarker data? I think I saw in your press release this morning that you plan to publish maybe a paper about brain atrophy and its direct correlation to cognition. Is that accurate? And is that some of the data that you may may not be presenting to to the EMA?

That's accurate. So the advantage of the biomarker is that the biomarker endpoint is objective and cannot be influenced by a patient the caregiver, or the physician, or anybody else as a matter of fact, because it's objective. And I pointed out that in analogy to oncology where you get drugs approved purely by the effect of the brain measure sorry, of the tumor measurement. And while, for example, the clinical effect was not yet significant, And that is something which we like to point out that the analogy is in Alzheimer, the clear pathological shrinking of the brain, which is one of the first features Alois Alzheimer himself actually identified his patients with Ultima, the first patient he assessed. Subsequent later on when he looked into the brain, he found this additional, you know, aberrant features of proteins than identified as a beta plaque or tau. But the first thing he identified was really that the brain shrinks and the holes, the gaps widen in the brain. And that's really the pathological logical consequence of a declining brain, less less functional brain. And it's like a lemon which is drying up. You cannot squeeze anything out of it. And that is really a strong objective biomarker and biomarker end point for demonstrating an objective effect of a drug and that was demonstrated with blacamazine. So we just make sure that gets visibility and and part of this is also a correlation analysis. That we are able to find that not only that there's a shrinking less shrinking of the brain, shrinking of the brain going along with blackamazin treatment, but also that correlates with each patient with a improvement in the respective regions. Of the brain's activities of the adascoct 13 subdomains, for example, For example, learning and and reading and writing as in one area of the brain, and if that is improved, in the clinical trial for the patient, that same region of the brain responsible for that if that also is less impaired in the active glycogen treatment arm compared to placebo. And if you can find this this further confirms the true effect of the drug. And that will be convincing in our opinion.

I I think that's really interesting. I'm definitely looking forward to that. And I think kind of related is in light of the semaglitude failure is that they reported that you know, that the drug had improved bio markers, amyloid, maybe tau. I don't recall about tau. But you know, the improved amyloid but had no clinical effect no improvement on CDR sum of boxes. And I think that I'm not sure exactly when there needs to be if there will be a time where regulators will no longer see amyloid equals, you know, better cognition or whatever. But moving along kind of on September, the company PR'd really impressive AppClear three comparisons to Prodromal. Populations and had a detailed follow on analysis of AbClear two and AbClear three subpopulations in a GWAS preprint a little bit later. AbClare three in particular appears to showcase an effective functional cure in early Alzheimer's patients and you covered the mechanisms of these earlier But can you give further color on APCLEAR one versus APCLEAR two and APCLEAR three? Specifically whether they were prespecified or exploratory and how regulators may or may not view these subpopulations in light of being exploratory or being prespecified. Is this something you can talk about?

Yeah. So the definition of a b clear one which basically is the wild type sigma one gene. Which was identified already in the beneficial effect of that gene, in the previous preceding phase two a study. Which was published 2020, we identified that patients with the sigma one wild type which represents seventy percent, seven zero, of the population, had a better response to blarcamesine than those with the respective mutation. It's a point mutation and that's how biology is. Thirty percent of overall population, that's not patients, but overall population has a one point mutation, r s one eight hundred eight sixty six, and this one mutation changes the confirmation of the gene makes it a little bit less viable or effective in its ability to restore homeostasis. Increase autophagy, which is the mechanism of the activation of blackamisines through sigma one activation as its ultimate effect. And so the patients with the wild type, the fully functional non mutated gene respond better. So this was identified in the phase two a. So we prespecified the analysis of the primary endpoint as well as the secondary and exploratory endpoints With these in mind, how would patients do in the phase two b slash three study? With the wild type sigma one. And that was prespecified, and we now define this as a b clear one. And we did indeed demonstrate or it was demonstrated that indeed that was confirmed Blacamazine increased effect of patients with that of seventy percent, roundabout is the number of patients, seven zero, which improved better than the patients with the mutation. And that is improving. So now ABCLEAR2 was the result of a pre planned in the trial. We did a whole genomicosome analysis. That means we looked at all patients in the study and analyzed their genes and genes expression and response to the drug based on the genetic profile as well. That is the DNA of all patients. And in this analysis, which was preplanned, we found to our surprise, unexpectedly, one gene showing up is a extremely strong driver of efficacy And that gene turned out to be the collagen 24 a one gene. And that gene, I explained it just before, is involved in the buildup of the extracellular matrix. That's really really intriguing novel science and underappreciated or overlooked up to now by the in the field because everybody always looks at the neurons or the astrocytes or the areas of active involvement in the brain. But the extracellular matrix is where all these neurons and astrocytes are residing or sitting on. It's like a a pavement, like a street. And if that street is not smooth, like a highway, or like a a pavement, then then this then this these neurons cannot function well. And we were able to find find them because the patients with the mutation of this colagene in gene in this extracellular matrix, not respond so well, to blackamazine, representing that they're not as viable as the respective wild type carriers. And the good news, though, is the collagen wild type represents seventy one patient percent of the overall population. And that was also found in our trials. We had run about seventy percent with patients with this cytology and wild type gene. So very intriguing new data, and that was, as a consequence, was preplanned in the study. Of course, not prespecified because we found it in the analysis of the phase two b slash three study.

Okay. And it's my understanding that Leqembi and Kisunla were both approved after a CHMP reexam, and that subpopulation data enrich their filing by conferring a more desirable like, safety efficacy axis. Is that true, and is this any way relevant to Anavex's current position with some of this data, the the ABC CLEAR two and ABC CLEAR three data.

It's it's it's correct. Both lecanumab and donanemab and these are run by large pharma companies. They had been a low prior approved in The US, reached the same point as we did just as we communicated a few weeks ago. And they underwent the same reexamination and were able to get approval. I don't want to I would say, make that that this is a guarantee for us because every review is complex and we are not able to anticipate or know the outcome of this re reexamination process, but the body pulls down to in the assessment of lecanumab and donanemab. Was the assessment and the judgment of benefit needs to outweigh the risk. Sure. And our our drug has safe has safety. It's has no ARIA. We talked about the efficacy, which we just discussed. But we cannot anticipate, of course, an outcome of the regulatory review.

Okay. Understood. And moving forward, will you be immediately refiling for the EMA reevaluation? To my knowledge, it took about three and a half to four months for the CHMP to give Leukemia and Kasimha their next opinions respectively. So maybe we could see something around April. Is that about what you're projecting?

That that's correct. We will immediately ask for the reexamination as soon as possible. And, again, while there's never certainty to obtain approval from regulators, we remain highly excited about the science and the data.

Okay. And, you know, being a small with a unique mechanism of action, it's probably difficult for you to garner support from the community. I recall that the European Alzheimer's disease consortium, Alzheimer's Europe, and even the US Alzheimer's Association kinda put together persuasive arguments for the CHMP to consider during the Lyckembian re evaluations. Does Anivex have any support like this? Are you aware of any organizations, key opinion leaders, or even patients from the trial attempting to persuade the CHMP to reconsider. Do you have that support from the community?

It's really not for us to make that move, and the community is aware of our of our drug, and we let them basically do what they think is appropriate. And what we only can do is point out the data and this is a process. And we are committed to this process. But also, very importantly, with this process, we gain also confidence with the regulators We are doing this in a partnership. We are doing this in a open discussion. We are are also getting the the ability to get feedback, which we need to move this forward in what way it takes to help patients addressing this unmet medical need.

Okay. Well, I see that we're, you know, nearing time. So to conclude for me, least, it's pretty obvious to anyone paying attention that, you know, Blarcamesine should likely be approved for early Alzheimer's patients and, you know, the the efficacy has been absolutely unprecedented in these megalithic effect sizes were achieved in a really small population, which should theoretically make it more difficult to do So I think it's a clear win for patients, caregivers, and payers, and I I think part of the problem the first time around may have been that it was sort of you know, piecemeal analysis and you're, you know, you're introducing analysis as you're going. But now that you have all analysis at your disposal, and a clear narrative, it's my hope that the company will use know, the reexamination to tell Barcambizine's story and earn the approval it deserves. So thank you for taking my call, and you have a good rest of day. Thank you.

Oh, we appreciate the kind words, and our expert advisers advises us also to proceed and so do the patients and investigators They also advise us to proceed. And we may remain committed to do our best. Thank you.

Yeah. Thank you, Jesse. And doctor, I don't see any further questions at this time.

Well, thank you. So we are thankful for your continued interest and trust in ANAVEX. Wishing you a happy and blessed Thanksgiving. But in closing, we like to continue to point out our focus on execution as we advance our therapeutic pipeline to potentially improve patients' lives living with these devastating conditions. Oral once daily blacaramazine has the potential to address high unmet medical need in early Alzheimer patients. With its clinically meaningful efficacy profile, of slowing cognitive decline by more than thirty percent and sometimes even higher for certain populations. Its acceptable safety profile as demonstrated in the phase 2bthree program. Thank you very much. And, again, happy and blessed Thanksgiving.

Thank you, ladies and gentlemen. This will conclude today's conference call. We appreciate you participating, and you may now disconnect.