Anavex Life Sciences Corp. Aktie

Greetings. Welcome to the PVG Asset Management Corporation Town Hall. [Operator Instructions] The conference is being recorded. I will now turn the conference over to your host, Patrick Adams. Patrick, please go ahead.

Thank you for joining today. We've got a pretty detailed presentation that's going to take us a while to get through all of it, but I think you'll find the information very helpful. And we are looking for your help, as shareholders, to help support us to turn around Anavex. Anavex, the board nominees, the four nominees currently on the board, own a total of 5,000 shares, three of which of those nominees hold no shares. I think this is a major misalignment with shareholders.

And we've seen very recently, and over the past, leadership issues and governance issues to this company. And again, we need your help as investors.

We'll be going over a number of different things today, talking about what needs to be done, how we're going to do it, and then how to vote your shares.

So, introduction. PVG began acquiring the shares back in September of 2024. We think that there is great value in the pipeline. We have very unique CNS, and unfortunately, the company has been misguided, not represented well by the board of directors. And it started with the EMA submission for Alzheimer's. So the Alzheimer's drug at the EMA was causing the stock to fall 35% in a day. We think the board could have handled this more appropriately and avoided this major issue.

So the CEO was terminated for cause, which set off some more lawsuits. One, an employment agreement lawsuit, but then another suit against the four existing board members. The major issue that we have recently is the appointment of a CEO with no prior experience as a CEO, and we can't really find any clinical achievements that she's had either. Termination of key people at the company. There's been a massive brain drain at this company. It's rather disturbing to see all the people that were let go, that were very knowledgeable about the drugs and the development process. The NASDAQ delisting notification, now the company's resolved this, but to me, if you can't report your financials on time, you're really not a public company, and we need to make changes to make sure this never happens again.

But because of this, it all put their ATM on hold for 12 months. As I mentioned, that there's no skin in the game from this current board. They don't own very many shares. I don't think they're particularly aligned with shareholders. They're not really focused on the biotechnology team that we've put in place. So, the stock has obviously really underperformed. The stock is telling investors basically there's a problem here and it needs to be fixed.

Now we went to the board, two of the board members. I had conversations and said, we're here to help. What can we do to help? That didn't go anywhere, so we had to file our nominees to replace the board. Again, please use the gold card to vote your shares. Now, we're going to go over remember our nominee versus their nominee. That's me. I'm Patrick Adams. I've been in the investment business for 40 years. I've done a lot of biotechnology investing.

It's a specialty. This is a very inefficient market. It's ripe with opportunity, but you have to know what you're doing. So 40 years, you learn something every day. I feel like I'm an expert on this particular area. We've done a lot of investing in the CNS group. I like to compare this company with a company called Axsome, which had private financing of the company, then it went public. And in 2019, as an example, the two companies, Anavex and Axsome, were at $2 a share. Well under their leadership, Axsome is a stock that's over $200 a share, and Anavex has gone basically sideways over these seven months, or seven years rather.

Ma, she comes from the telecommunications space. She recently did a SPAC that has fallen now 99% value. So a negative 99% return. She owns no shares in Anavex. And I have another slide just so you can visualize what's occurred there, and we'll do that after we go through the nominees. Rene Mora. Rene, can you please go over your background?

I guess I can. I hope everyone can hear me. So I'm Rene Mora. I am a physician scientist by training. I have an MD and a PhD from the University of Chicago in biochemistry, practiced for a number of years as a physician scientist in the Harvard hospital system, in the area of pulmonary and critical care medicine, where again, I was an NIH-funded scientist at Harvard Medical School for a number of years. Joined the financial services industry after a few years at Harvard, where I joined Leerink from its fledgling days as an early organization, spent a total of 20 years at Leerink. First 10 years building the MEDACORP expert network, which included heavy representation of experts in the regulatory space, and where we actually published a regulatory newsletter in addition to carrying out market research and carrying out deep diligence on emerging biotechnology and pharmaceutical products.

After 10 years on the MEDACORP side, I joined what was then the incipient effort at Leerink to build an investment banking effort. And I spent 10 years there helping and build that effort.

I will point out that 15 years later, Leerink is now the number one investment bank in the United States for biotechnology and biopharma financing. I retired from Leerink in 2020, went over to the buy side where I spent five years at Monashee, a $3.5 billion investment hedge fund managing the healthcare portfolio both on the public and the private side. I do have board experience; I was a board observer at Hotspot Therapeutics, one of these companies that Monashee invested in as a crossover investment. And I currently sit on the board of trustees of the University of Chicago Medical Center, which is a multi-hospital system with 20,000 employees and a multi-billion dollar budget.

Certainly that's a solid background, very experienced. Peter on their side is a physician. I'm sure he's a nice guy, but I wouldn't have my doctor on a board of a biotechnology company, personally. Next slide, please. John, please give your background.

Thanks, Pat. So my name is John Boris. I am also a scientist by training, a degree in pharmacology from Philadelphia College of Pharmacy and Science in Philadelphia. Interned through the hospital networks throughout Philadelphia. After pharmacy school, pivoted right directly into the industry, started my career with Eli Lilly and Company. The tenure there was mostly concentrated on the central nervous system side through the launch of the antidepressant Prozac, which had significant off-label use and additional psychiatric type indications. After spending approximately four and a half years at Lilly, pivoted to Warner-Lambert, where for seven years ran the neuroscience portfolio at Warner-Lambert prior to the acquisition by Pfizer.

Some products that were in the portfolio there were the first Alzheimer's drug Cognex in addition to Neurontin, Lyrica on the major pharma branded side and then we also had some orphan disease drugs like Fosphenytoin for the treatment of status epilepticus which was launched throughout the U.S. Hospital Network. Upon completing that tenure, pivoted to Wall Street. Started my career on Wall Street at Morgan Stanley. Worked for a person by the name of [ Glenn Reicin ], who is pretty well recognized in the MedTech Hospital supply area.

After three years at Morgan Stanley, pivoted to Merrill Lynch. Merrill Lynch. We were a part of the I rank number one team in major pharmaceuticals. Post 9/11, approximately a year after that, pivoted to Bear Stearns where I was the lead analyst, major pharma, specialty pharma and covered some small biotechs. At Bear Stearns until the implosion there, then pivoted to Citi, where where we were co-lead analyst at both shops there I was institutionally recognized by the buy side for the work that we had done.

Following that 25-year tenure, pivoted to banking, spent approximately two and a half years in banking, and then from banking went on to do asset management where I invest currently in both public biotechs and private biotechs, and especially those that are within the CNS area.

And then on the other side we have Van der Velden part of the audit committee that issues with the [ financials ]. He also comes from the telecom space. And I tell you, as a biotech investor for a very long time, I don't want to get on a board. Next, Curtis.

Thanks, Pat. A quick word on my background. I started my career 35 years ago in clinical research at a biotechnology company working with Dr. Rosenberg's lab at the National Cancer Institute. I then worked for several years with the U.S. Patent and Trademark Office as a biotechnology patent examiner. And I've spent decades in biotech and pharma investing in equity research at various firms, including Discovery Capital and Citadel.

I was recruited to the board of Alaunos Therapeutics, a publicly traded company, as it navigated a significant transition, and I served as its interim CEO and principal financial officer. So I've sat in the seat of studying the company and managing its finances through a difficult stretch.

I also serve on the board of Wondering with Willow, a nonprofit supporting families affected by Rett syndrome, which keeps me close to the rare disease community that matters so much to this pipeline.

If you look at the right, the incumbent, Axel Paeger, has an executive record in hospital group operations, not drug development. Per the company's own filings, he holds no shares in Anavex. He has no skin in the game. That's the difference this slide shows: relevant experience and real alignment with shareholders versus neither.

Thank you. Jason. Jason, you probably need to unmute your line.

Operator, can you unmute me?

We can hear you.

Okay, great, thank you. So very similar combination of experience to John. Started my career as a chemist on the bench with Warner-Lambert, went to Schering-Plough, launched INTRON_A for hepatitis C, as well as Claritin, so I got a lot of commercial experience there. Came back, started a career on Wall Street, spent many, many years as a sell-side analyst, transitioned to the buy side and ran a portfolio making investment decisions with Susquehanna for seven years and then made a transition to microcap biotech. I worked in the cell therapy space, was very active, learned a lot about how to raise capital when you're a microcap biotech, and then decided to transition back to the sell side where I remain today.

I have focused over the last 10 years in the CNS space and actually was part of the original team at Maxim that took Anavex public. So, you know, I've followed this company very closely for its entire life and, you know, I have seen both the pitfalls in data and clinical trials, but more recently, the lack of communication with a management team which I think has become an exacerbating effect to the stock and to the stock valuation.

And then on their side, we were kind of excited to see this gentleman's background until we realized it was in oncology rather than CNS. So unfortunately, it's not the right fit for this company. Ralf von Ziegesar, he – on the next page, page nine -- he's 30 years experience in the asset management area. He's got a very impressive background. He was an investment officer at Société Générale, among other very well-known investment companies. He runs a multifamily office in Germany. He's our guy in Germany to help deal with the investors and to kind of lead that, or in Europe to lead that, to obtain more investors and to talk to investors in that continent.

On the other side, Patel, he's into acquiring companies and doesn't have any real focus on biotech that we can see. So we've got a really good guy on the investment side in Europe on our side.

Now page 10. Okay, so we're getting -- on page 10, I just wanted to show you this chart. Ma's company. So through her SPAC, she bought a company called Mobix Labs. It's a semiconductor company. The SPAC came out at roughly $100 a share, like most SPACs do. This stock is now down to about $1 per share.

And then the cash over on the right-hand side of this chart, you can see it's about at zero. So unfortunately, we see these things happen in the biotechnology space, that boards or executive teams allow the cash to dissipate to a point that they become. And that really just kills the stock.

Next page, major issues. So the company says that they are moving forward with the Alzheimer's indication and we support that. However, there's only $118 million in cash. It seems like a lot of money, but the Alzheimer's trial is going to cost roughly $150 million. So it's a little bit of a disingenuous sort of plan in place.

The first thing that has to happen is they need to raise them up. So in our view, the company has poor governance, evidenced by the SEC filings and material weakness and internal controls over the financial reporting, which has resulted in the company not being able to use the market equity financing. That's the ATM. So they can't go to the market to do that. And they've raised about $36 million for this fiscal year prior to this occurring. The company also employee litigation, brain drain medical experts, inexperienced executive leadership, and limited clinical experience as well.

We believe that just changing two board members as what they're proposing and hiring a first-time CEO is not going to fix the problems. So as the cash evaporates and the intellectual property time is ticking away, Anavex needs to act ASAP. We need to get this fixed right now.

So we think the stock, as you can see, is going to spiral. And the cash is going to tick off over time. So we need to get going. According to the company's proxy that was put out on 8-10-26, the new rookie CEO has no prior experience leading any company, which we've already PVG has a positive bias toward the pipeline, but if the company can't convince us, which we have a positive bias towards, they're not going to be able to convince other investors either. Why, we could just sell the stock, move on. We've got other really good ideas. But we view this as kind of an [ Axsome ], a $2 stock that can become a $200 stock.

So we see the upside and we think if we put the right team in place, we could have a very fruitful return and bring some really good drugs to the market. So the company has a pipeline of potential drugs and very large unmet medical needs such as early onset Alzheimer's, Parkinson's. The company has two rare disease drugs that will need some funding regardless, so you just can't move forward without funding for these drugs as well. We believe voting for PVG nominees is the safe bet. We have submitted a wealth of deep biotechnology knowledge, financial markets, business acumen, banking, et cetera.

We think we are highly motivated. Our team is aligned with shareholders and bringing in executives. We will bring in executives needed to be successful to rebuild this company, basically.

So we see the upside, and we want you to vote for our slate of board of directors. So Jason, we'll let you take over for the next slides 12 through 17. Thank you.

Operator, can you unmute his line please? Jason's line?

Jason is unmuted.

Okay, Jason. Not hearing Jason, I'll take over until we get the line fixed, I guess. But the shares have underperformed the biotechnology sector by a wide margin. So this is May 5th through July 23rd. So when these announcements were made, the stock actually dipped 28% versus the biotechnology index up 10% and the S&P XBI biotechnology ETF up almost 14% over that period of time.

Now, this is on page 14. Anavex has dramatically underperformed the peer group of companies over a one-year period. You can see there, the gold one is the company we've mentioned before, up 84% where Anavex is down 63%. So the market is speaking very loudly. Three years, again, Anavex down about what is that, about 50%. And again, Axsome up 204%.

Page 16, this is a longer term chart, and you can see over a five year period, Anavex is down about 80%. Other peer companies [ Axsome ] nine fold over that period. Page 17, three years, again, Anavex underperforming the XBI, IBB, two broad market biotechnology ETFs, underperforming in a major way.

The XBI up 117%, the IBB up 72%, and Anavex down 59%. Okay, so we're on page 18, on page 19. So the first thing we think we need to do is reconstitute the board. We need to bring in people that have biotechnology experience, that have been doing this a long time, have executive experience, have been successful. So that's what we're doing. Obviously the priority is the pipeline and to move forward the key indications.

So we will as a team go through each drug and determine what needs to be done to move it forward and the financing that needs to happen. We don't want to come in and disrupt anything that's happening at the company.

Let things continue as they are, as long as they're appropriate, but let the current development, if there's things that are happening, go forward. We think it's a really good idea. There's what's called genetic super responders, okay? We think that getting that for compassionate use for Alzheimer's can really show the regulators real [ world ] that this drug has some strong efficacy. So that's something that we would like to get going as soon as possible.

And then probably focus on part of the Rett indication, potentially the Fragile X, and then determine what to do. We're moving the Parkinson's forward, which the company has, it looks like they've killed that off, but move the Parkinson's forward and the schizophrenia as well, maybe in some sort of partnership agreement. So, the key is to de-risk these trials, to set them up for the as high a [ holiday ] of success as possible.

And with a new CEO hired and a new team in place, we would also encourage the management team to bring in the best and brightest to run these trials. It's important to shareholders that we don't get diluted with the stocks currently doing with what we've experienced over the past several years by a lot of losses that have occurred, but we want to do as much as possible and non-dilutive financing.

I mentioned this, that the company needs to rebuild the clinical team. Well, we lost a lot of good people. Nine scientists or nine executives were fired, excluding the CEO. So we want to do a proper transition of all that knowledge that we lost with the firing of these key people. And we think this is board of directors 101.

The board needs to have skin in the game. The board members need to own stock and we want to have an active board that owns outright shares in the company that we buy with our own money, expertise in biotechnology, corporate governance, it's critically important.

Addressing the bad governance, and then markets, capital markets experience, dealing with Wall Street there are [indiscernible] out there, right? And we're going to try to take it up at much lower levels. Out there, right? And they're going to try to take advantage of buying the stock at much lower levels. And we have to be aware of that and protect our shareholders. So there's an issue with the executive committee that was formed. The board decided that the company is best off not allowing the board to participate, having an executive committee to take over control of the company and make all the decisions, and basically excludes the minority board members from having any, excuse me, by having any input. So this is reckless. This is what we believe that's occurring at the company. Again, we think all direct officers of the company should own shares in the company outright by law.

So our plan, this is on page 20. Our plan is, one, is to hire an IR firm that's not focused on real estate, but it's focused on biotechnology. So we're going to hire an IR firm. Probably a great little IR firm, but it's not the -- they don't know the biotechnology investors. They don't know the big funds, which we don't think they do, and the smaller funds and the family offices that would probably would like to be in the industry to get some confidence. Additionally, to do one earnings call a quarter. Recently, Anavex has done no earnings calls. But we want to do one earnings call a quarter, talk about the pipeline, and the path. We want to do another conference call for investors, one a quarter, with a key opinion leader about the drugs we have.

So one specific drug per quarter by a key opinion leader. These are obvious things that the existing team should be focused on, but we need to move these drugs forward. We need clinical success, so a strong team to run these trials. We need to improve the patents of these drugs. So there's ways of doing this, we need to extend because we've let too much time expire on some of these drugs. Manufacturing and commercialization. We've seen over and over again in the biotechnology space, when those plants aren't ready to go, it delays the launch of these drugs by roughly a year.

So that's we had in manufacturing and it's done properly. Partnerships with Big Pharma, we're rather surprised the company hasn't done this already.

So we could get non-dilutive financing this way and still own a significant portion of that drug. Most important, a successful capital plan to commercialize these drugs. We believe Anavex's current leadership has underperformed. Shareholders need experienced leadership and a credible, actionable plan. The PVG group is committed to this. We're going to be active board members. So Curtis, please take over at page 21.

Thanks, Pat. This slide is a summary of our plan organized around three priorities. The first is leadership. This is where it starts. As Pat stated, we intend to recruit an experienced CEO who's a proven expert in CNS and rare disease. Rebuild the management team with high performing professionals and rebuild the clinical team with real team depth. And critically, we will require meaningful stock ownership, skin in the game for every director and officer. Leadership that owns the stock thinks like an owner. Second, advance blarcamesine. We prioritize early Alzheimer's disease, recognizing that it needs funding, and we establish a credible regulatory pathway built on direct feedback from both the FDA and the EMA. There we work to accelerate approval and commercialization, and we strengthen the patent protection across the pipeline so the value we create is durable.

And third, unlock the rest of the pipeline value. We pursue non-dilutive financing and strategic partnerships. We explore partnering the Parkinson's and schizophrenia assets, programs with encouraging data that the company simply cannot fund alone. We re-engage European regulators and address the CHMP's concerns head on rather than walking away. And we preserve and leverage the institutional knowledge built over years of investment, knowledge this board has been letting walk out the door. The objective is simple, and it's at the bottom of the slide. Maximize the value of Anavex pipeline for shareholders while advancing therapies for patients.

Those two goals are not in tension. They're the same goal. Now on slide 22, this is the summary of the first 100 days across six work streams. I won't read every line. You have the slide, but let me hit the priorities in each. Leadership and management, hire that experienced CEO with a genuine following among institutional investors, rebuild the clinical team without disrupting the trials already underway, and conduct a proper transition, including with the nine executives who were let go so we recover the institutional knowledge that's been lost. On clinical development, make sure the trials are designed for the highest probability of success with independent outside input. Stand up a special board committee with real clinical expertise to oversee trial risk and de-risk the Phase III Alzheimer's design, including proper patient selection, catching patients early, rather than moderate, which is common and costly for in Alzheimer's trials. On capital and partnerships, raise money at a higher stock price, or non-dilutively, not from a position of weakness. Partner with Big Pharma on the indications we can't fund alone and do a complete review of every asset, its financing needs, and its patent life.

On governance, legal and regulatory, address the outstanding litigation, put real board oversight accountability in place, and require meaningful stock ownership from board and management. On investor relations, communicate actively and credibly with shareholders in the scientific and financial communities, and bring in capable IR and PR firms to rebuild visibility. And underpinning all of it, accountability. An active board that expects results and directors and management who put their own capital into this company. That last point ties the whole plan together. Thank you.

Okay, so page 23, why is PVG seeking change? Page 24. This is a little detail-oriented, and I'll do my best to hit the important points. But I've seen this over and over again. And the sharks start to circle. And so what we're seeing is a spiral down in the stock. Wall Street has little confidence in what's going on currently. So what happens is stocks tend to follow down the cash.

And as we go through time, they've discussed that the cash will last until March of 2028, approximately, and then they'll be roughly out of cash. So what happens is the stock follows the cash down, has to do a 10 to 20 or whatever reverse stock split to get this stock back up. They don't have a good institutional following. So a financial buyer of the stock loaded with warrants typically comes in and takes on, keeps the warrants and sells stock. So this occurs over and over again in biotechnology, and like I said, I've seen it over and over again. So, we believe the existing board lacks the alignment with shareholders, has demonstrated poor corporate governance as a background in other industries, not biotech. Lacks capital markets knowledge and, you know, frankly how they've handled the firing of the CEO and the transition of the business and reporting the financials and not being able to use the ATM that, you know, demonstrated poor business acumen. So we think we can do a lot better. So it's important to bring in somebody knowledgeable on CNS.

And we're not saying we're going to fire the rookie CEO as soon as we get there. I'm sure there's things that she could do to help. We need a transition. We need to bring in a new CEO that has that following and experience, somebody that's been there, done that before, right? Okay. It's really important to have that history in CNS, in our opinion. Alzheimer's trials are very complicated. So one of the things that was disclosed in the most recent filings, that is a little bit concerning to us, is the weakness controls at the board. So that audit committee and the board and the CFO did not have a proper process to get the information from the CEO. So there's this issue that was at fault. And more or less, the audit committee, the board, and the CFO really are in charge of this process. It's become a problem, it's costly, stock went down because of it, they're probably going to have retaining employees or hiring new employees.

This was in their 10-Q filings. So by losing, by not filing the financials, I just wanted to focus on this point. They've raised $36 million ATM. That's an S-3 filing. So that S-3 filing is dead for a year. To get more money, they're going to have to go to Wall Street and get investors to actually do a stock offering. So at this point, it's going to be very difficult with the team that they have in place that doesn't have a lot of credibility, and you can see it in the stock price. The Executive Committee, as I mentioned, is comprised of Ma, van der Velden, and Paeger. So two of the three are from the telecommunications department and the other one runs a hospital.

And so we have this committee that's basically running the board and the company, to our knowledge, and they don't really have experience in running these type of companies. So we need to refresh the entire board. If these three individuals stay in place, then what we read from their proxy statement is that this committee can stay in place indefinitely. Then there's been some nonsensical statements, I'll say nonsensical, that's a polite way of saying it, that we are seeking control of Anavex without a credible plan. I think we went thoroughly through our plan. I think it's very credible. And the other, there's more, there's other statements that they've made that we're not paying a premium for the shares. Well, we've paid a big premium.

The stock's down considerably. We're not acquiring the company. We're not taking the assets. We're investing along with everybody else. We want to see the stock go up. And then the other thing that we hear is that the former CEO is paying us to do this. That's just completely insane, okay? Wouldn't consider it. And, you know, we think it was probably time for the former CEO to move on. He's been there 13 years. He brought the company to where it is, had some success.

We need a new team to come in and take it from where it is currently. So, this is page 25, why PVG is seeking change. Okay, so we spoke to four of the six board members, a number of different former employees, their medical team, analysts, bankers, long time investors in this. And we know what's going on at the company. And we really think that the board needs to be replaced. So looking at the big picture from December 2023, the Alzheimer's data, and it was good, not great, but it was good. You know, they made some mistakes in the trial.

Well, three years, roughly three years have gone by, and they spent $130 million. And to our knowledge, really nothing has. So we look back at this and we say, if there was an active board, a board of new biotechnology, they would have asked the question, or they would have pushed forward the Alzheimer's trial or gone a different path. So why didn't the board push forward the Phase III trial knowing the company had to go to the EMA and the EMA was going to require them to do another Phase III. That was well known. The FDA and EMA required them to do another Phase III trial. So why didn't the board instruct the company to do so? So obviously discuss this in detail. Well, two of the four board members that are left are from the telecommunications industry. I think they're probably good people.

They never ask the question, in my mind. They're not from biotechnology. So page 26. So we're disappointed in the hiring of the new CEO. Like I said, again, she probably can be helpful to us transition out. We need to get a new CEO in place that has experience. The brain drain at the company, unfortunately, it happened the way it did. We understand there's a lot of information that wasn't passed along.

There needs to be comprehensive transition of all the knowledge that left the company. And then, importantly, we need biotechnology people involved in the company that know how to ask management teams tough questions and to be actively involved in monitoring. And lastly, we need an IR firm that's focused on biotechnology. Okay, so Rene, you're going to hit this very quickly, page 27.

Yes. So in the interest of time, this slide illustrates clearly the brain drain that has occurred at an event that Patrick was referring to. Last week at a conference, I happened to be in a meeting with Al Sandrock, who was at Biogen for 21 years and was chief medical officer when he left the company and basically was in charge of all research. He talked about the key pillars to drug development in central nervous system diseases. And one of his three key pillars is you need to have the right team in place in order to get these trials done. They're complicated, they're difficult, and you need to have the right personnel. Right. Without prejudging the qualifications of every individual on this slide, you can just see that for a company whose task is supposed to be to carry out that clinical development of CNS drugs, that these should be the critical people that you need in order to carry out the clinical trial. So if you've chosen to lay off all this group of people, you need to have a credible plan in place as to whom you're going to replace them with.

And again, we're not going to prejudge exactly where these individuals stand, but I think it's clear that we need to look very carefully at the personnel and make sure we... Obviously, the CEO will do this, but with the oversight of the board, we need to make sure that the right team is brought back into place.

Thank you, Rene. Page 28. We've talked about this. You can read it for yourself, but it goes through what happened with the audit committee, the board, the chief financial officer, the CEO, and the processes that were delinquent. And it's causing a lot of concern. We're concerned it's going to create some legal liabilities as well. It's a problem, okay, and it's not been fixed yet. It doesn't appear to be. Again, under 10-Q, it was filed. You can see on page 12, this is rather disturbing for me, that they gave back a Michael J. Fox grant for Parkinson's. The Parkinson's, you can read the press release that was dated March 17, 2026, that there was a strong signal of fiber density nerve growth back for the dopaminergic area of the brain.

I think that's really interesting. So Jason, if you're available, please do pages 29 through 35. Can you please unmute his volume?

Hello.

Okay. We can hear you.

Okay, great. So on page 30, board alignment, share ownership, it's a very, very simple slide. Does the board have skin in the game? And the answer is no, they don't. And it's one of the first criteria when you're marketing a company to the institutions, to the buy side, that they'll ask you. So with no skin in the game...

Okay.

Yeah.

Okay, we can hear you again.

Okay, so it's critical that the board have skin in the game. The other thing, and Patrick just mentioned it, was the IR firm and management's communication style. And quite honestly, it's very important to be always dialoguing with your investors, and that's not something that's been happening. Slide 31, reported ownership figures. Again, it shows that this is almost an afterthought for this executive board and it kind of begs the question on why are they so adamant in fighting Patrick and fighting the support? I don't quite understand it. What are the company guidelines? Slide 32. The company clearly has not structured the guidelines towards ownership of the stock. Again, institutions want to see that management, CEO, CFO, all executive management and the board have financial incentives to perform, and we just don't see that as part of the overall policy. And the last slide, slide 33 that I'll touch on, is the executive committee and the fact that there's active litigation going on.

And, you know, the executive committee is characterizing this as a non-issue. In fact, they're not even really addressing it. And I think that's a mistake. So with that, let me turn it back to Patrick.

Why don't we go to slide 36, and then Curtis will take it from there.

Alright. Great. Thanks, Pat. So that's our plan and now it comes down to a decision, your decision, and it's the one on your ballot. You'll be voting on the gold card. That's the PVG slate, Pat Adams, John Boris, Jason Kolbert, Rene Mora, myself, and Ralf von Ziegesar. Let me show you exactly who these people are and why we believe they're the right board for the next chapter of this company. Okay. Slide 37. Okay. Alright. This is the whole case in one picture. Across the top are the five things that this company needs on its board: experience in capital markets, biotech investing, public company leadership, drug development and regulatory experience and governance. Down the side are our six nominees.

And if you look at the coverage, every skill Anavex needs is represented, most of them several times over. Below the matrix, we've laid out the actual track records, public company experience on the left, private on the right, because we're not asking you to take our word for it. Pat Adams brings decades of biotech investing in public company board service. Rene Mora is a physician and MD PhD with two decades in healthcare and a seat on a major academic medical center's board. Ralf brings 30 plus years of asset management and multiple company supervisory board roles across Europe. John Boris built a four-decade career inside the pharmaceutical industry itself. Jason Kolbert has spent more than 25 years covering biotech and neuroscience specifically.

And, of course, my background is in biotech investing and equity research, and I've served on the Board of Alaunos Therapeutics, a NASDAQ company, as I've navigated a major transition, including as Interim CEO and Principal Financial Officer. I'd note, Alaunos had no material weakness determination, unlike the situation we're addressing here. The point of this slide is simple. This is a board built for the actual work in front of Anavex, the science, the capital, and the governance.

Slide 38. Skills only matter if they're put to work in the right place, so we've already thought through how this board should organize itself. This is our proposed committee structure designed around three things that will make or break this company.

Oversight, capital, and the pipeline. You can see it's a working board, not a ceremonial one. The audit committee, Patrick Adams, myself, Jason Kolbert, compensation, Jason Kolbert and John Boris. Nominating and governance, Rene and Ralf. And then the committees that speak to what's unique about Anavex, we're going to have a dedicated pipeline development committee, which will be Jason, Rene, John, and myself, because the science deserves board-level attention, a finance committee focused on the capital plan, and an executive committee structured around collaboration, not the concentration of power in a handful of hands that we've criticized in the current structure. Every nominee carries real responsibility here. This is a board that shows up to work on day one. Back to you, Pat.

Page 39, Summary and Conclusion. So we hammered this pretty hard, stock's down from $30 back five years ago to under $3. Lost a lot of money, corporate governance problems, change is needed. On page 41, we're not seeking control. We're shareholders. We just want to make this company work. Page 42, enough is enough. Let's get this going. And then lastly, our sources and required disclosures. You can please read through those at your convenience.

We want to leave some time for questions. So we've gone a long time now. So why don't we open it up for questions from the audience. We'll try to take a handful. Operator?

[Operator Instructions]

So, Pat, a question that was asked from the audience was how is it possible that the current board of directors has no experience in getting any drug through the clinical development process?

Well, you know, if you look at some of our candidates, right? We don't work in the clinic, but some of our candidates have been, has some very impressive track records. So John launched Prozac. Everybody knows Prozac. It was a huge drug. Jason launched Claritin in Japan. Curtis has been intimately involved in a biotechnology company. And you know what? As you're an investor, obviously, I don't do the work, but I know all the problems of other Alzheimer's drugs, I've seen it, I lived it, I know how they screwed up. So you don't want us to run clinical trials. That's not why we're here. We're here for oversight and to ask tough questions and to make sure they're hiring the right people to do it.

Got you. Okay. And how will you raise money for the Phase III trials?

Well, I was working on that last night, actually. So I'm here in New York, talked to some bankers. We will, we will have to do that. We want to do it in a non-dilutive fashion. If not, then we're going to have to go to Wall Street. We need somebody very credible running the company that brings a following, so like I've been invested in other companies, certain CEOs that they come and ask me for money, I'm going to invest with them probably not even knowing what they are even planning because I know they're successful people. That's what we're looking for. So we've got a number of banks, so being in the industry for a long time as everybody else on this board, we know a lot of Wall Street people that would probably love to work with our Board of Directors.

Do you have a CEO that you would consider replacing the current interim CEO with?

Oh, you know, obviously, we'll have to do a complete search. And we couldn't divulge anybody at this point. It wouldn't be fair to that person. But that's the highest priority we have at this point.

Okay. And will you confirm that Missling will not be involved with our Gold Card?

Absolutely.

Okay. What do you think is the most important thing that shareholders should take away from the call before the meeting?

I think that they need to realize the path forward from each group. One group that's in place currently, they're going to struggle. Our group, we've designed it for turning this company around. So we want to give this company a real strong shot. We want to see it be successful. So there's a lot of work that needs to be done. And we've seen the trend in the stock over the years, the mistakes that have been made. We need to resolve those, and we need to get the thing going in the right direction.

Okay. I think that's all we have for questions.

We thank everybody. Thank you very much. And again, we need your support. We need your vote to get this going in the right direction. And if it doesn't happen, unfortunately, we think the stock's probably going to go lower. Take care everybody and reach out if you have any questions.

And this concludes today's conference and you may disconnect at this time. Thank you for your participation.

Welcome to the Anavex Life Sciences Corp. Business Update Conference Call. [Operator Instructions]

I would now like to turn the conference over to Alex Arzeno with SCR Investor Relations. Please go ahead.

Hello, everyone, and thank you for joining us on the call today.

Before we begin, let me remind you that we will make forward-looking statements on this call, and actual results may differ materially from those expressed or implied in these statements. These statements are made as of today, September 9, 2026, and we undertake no obligation to update them, except as required by law. Please refer to our SEC filings for a detailed discussion of the risks and uncertainties affecting our business.

I will now turn the call over to the Chair of the Board of Directors for Anavex Life Sciences, Dr. Jiong Ma. Jiong, please go ahead.

Thank you, Alex. Hello, everyone.

I have had privilege of serving as Board Chair at Anavex since 2023, but I have been part of the Board of Directors since 2021. There is a shared passion among all of us at Anavex, the Board, management, and employee. That is to advance blarcamesine ANAVEX 2-73 forward to help patients, families, communities suffering from central nervous system diseases with high unmet medical needs.

On behalf of the Board, we would like to thank everyone for their continued support and understanding during this critical transition period. We were able to file our 10-Qs in late August. Now we're back in compliance with Nasdaq.

We are excited to conduct a brief call today to outline the company's path forward on all three indications: Alzheimer's, Rett syndrome, and Fragile X syndrome. We plan to return to our regular cadence of quarterly conference calls, including Q&A, when we conduct our fourth quarter call in November.

Our intent today is to let shareholders hear directly from Dr. Terrie Kellmeyer. Since being named as interim CEO in early May, she and her team have been working diligently and efficiently on our new strategy forward.

I will turn the call over to her now.

Thanks, Jiong.

It is both a privilege and a responsibility to speak to you today as the interim CEO of Anavex. I have been eager to address our shareholders, and I am excited about the platform given to me today to do just that.

I want to be direct about 3 things from the outset: where Anavex stands today, the company's path forward, and the foundation we have to execute our strategy with confidence.

Our conviction in blarcamesine has not wavered, and if anything, our confidence has only deepened. We stand firmly behind blarcamesine's potential, and the scientific evidence continues to support a promising path forward.

We acknowledge there was a delay in the company's second and third quarter 10-Qs, which was the result of the termination of our former CEO and the ensuing review by the Special Committee. As a result of that review, management, in consultation with the Audit Committee of the Board, reassessed the effectiveness of the company's disclosure controls and procedures and its internal control over financial reporting as of our fiscal year ended September 30, 2025. We concluded that certain deficiencies constitute a material weakness, and as a result, we also concluded that our disclosure controls and procedures were not effective.

We have developed a remediation plan that will be overseen by our Audit Committee. The plan is further detailed in our Form 10-K/A filed on August 28. We are now current in our SEC reporting obligations, and we were pleased to receive official confirmation from Nasdaq last week that the company has regained compliance with Nasdaq rules. This is a strategic pivot point for the company, and going forward, we will be executing against a clear, focused development plan.

I have spent my entire career in drug development. Over nearly 3 decades, I have built and led clinical and regulatory functions across the full life cycle of drug development, from IND through approval and commercialization, at companies large and small, across multiple therapeutic areas. I understand how to work collaboratively with regulators, how to build a strong and regulatory-compliant scientific and clinical plan, and how to lead the team to execute it. That is the experience that I have been bringing to bear each day as we are charting a path forward for blarcamesine.

Now onto the science. I have spent the last several years immersed in the science and clinical data behind blarcamesine ANAVEX 2-73, our oral sigma-1 receptor agonist and lead investigational asset. The sigma-1 receptor modulation is a biologically plausible mechanism with relevance across neurodegeneration and neurodevelopment, and the data generated to date have given us reason to continue investigating blarcamesine across Alzheimer's disease, Rett syndrome, and Fragile X syndrome. I know this program intimately: its strengths, its data, and I know what is needed to advance it.

Advancing blarcamesine for the treatment of early Alzheimer's disease is our top priority, and our focus is now on engagement with the FDA to align on a clear U.S. regulatory path. We have taken the regulatory feedback we recently received from the EMA as constructive guidance, and we are incorporating it into our planned discussions with the FDA regarding our Phase III study design and the overall development program for blarcamesine. Our goal is to now achieve a strong, well-aligned study design across both regulatory agencies.

I'd also like to mention that we recently refreshed and streamlined our Scientific Advisory Board. We now have a focused group of Alzheimer's disease key opinion leaders and treating physicians to help us advance our lead program forward.

As Jiong mentioned, we have also committed to 2 other indications that we believe have the greatest chance for success: Rett syndrome and Fragile X syndrome. With the FDA having already granted Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation for blarcamesine in Rett syndrome, we believe we have a solid foundation to move forward with initiating a Phase III study for adult participants, while working with the FDA in parallel to align on the inclusion of pediatric participants. In fact, I'm happy to announce that we've just heard back from the FDA, and we have been granted a meeting with the agency to discuss adding our pediatric population to our Phase III study. This is great news and progress toward our overall goal of aligning with the FDA on all of our programs.

When looking at the Fragile X program, we believe in the potential here. We have begun allocating resources to our Fragile X clinical program. The IND for Fragile X syndrome is expected to be submitted in the next couple of weeks and will be supported by the Orphan Drug Designation already granted by the FDA.

We've heard questions from investors about the status of our programs for schizophrenia and Parkinson's disease. We have paused development on these indications, and given our cash on hand, and to be fiscally responsible, we've decided to focus our resources on the programs that we believe have the greatest potential for success, which are the 3 core indications we have laid out. We believe this is the strongest strategy to create long-term shareholder value.

Our mandate is straightforward: focus the company, apply rigorous discipline, and let the data lead every decision, while providing transparent updates on the progress being made across all 3 indications.

Anavex enters this next phase with a strong cash balance and no long-term debt. We expect to be disciplined stewards of capital, investing where the science and regulatory pathway are clearest, building the right team to support our programs, and focusing on the opportunities that we believe will create long-term value for shareholders. We will move in an efficient and effective manner, putting our cash toward activities that we believe will yield results that will make us an attractive investment and potential partner.

To support our endeavors, we plan on attending scientific conferences, as noted in our third quarter earnings press release. We are also beginning to build out an investor conference calendar to engage with the appropriate audiences.

Next, I want to take a moment to speak directly to our long-term shareholders, as well as our covering analysts and partners. Many of you have supported Anavex through years of hope, uncertainty and disappointment, and you have never lost your belief in the underlying mission of this company. I know that the communication you received in the past felt incomplete, overly optimistic, or disconnected from the level of detail you deserved as supporters of the company. I want to be direct with you. That is not the standard we intend to operate by going forward. We intend to earn back your trust through clear communication, decisive action, and a strategy built around giving our programs the best chance of reaching patients.

That starts with a credible regulatory road map. We are committed to giving you a clear view of how we are prioritizing resources, time lines, regulatory interactions and next steps across our programs and the jurisdictions in which we operate. We will avoid ambiguity, overstatement, and unexplained silence and we will not leave you guessing about the status of our programs. Even when the news is difficult, you should expect direct and disciplined communication from this team, delivered candidly, confidently, and with humility. Above all, we are holding ourselves to a new standard of accountability, transparency, statistical rigor, strategic openness, and respect for our shareholders. We firmly believe that we can right this ship.

I now want to take a moment to recognize the team at Anavex. Through a period of significant uncertainty, our people have continued to show up, support the science, conduct rigorous clinical work, truly demonstrating the commitment we all have to the company's future. That kind of dedication is not something you can manufacture. It reflects a genuine belief in what we are doing, and why it matters. I am proud to lead a team of talented individuals who remain focused on the work, even when the path is not easy, and I am committed to earning and sustaining their trust as we move forward together. In addition to our talented internal team, we are actively building our leadership team with experienced leaders with relevant clinical trial and regulatory experience to support our goals.

At the heart of everything we do are the people we are working for. Nearly all of us have been touched in some way by Alzheimer's disease, be it a parent, a grandparent, a neighbor, or a friend. We understand the particular heartbreak of watching someone you love slowly become unreachable. For families living with rare diseases like Rett syndrome and Fragile X syndrome, the challenges are no less profound. These are often children, and the parents and caregivers who love them are counting on the science to move faster, to do better, and to not give up. We take that responsibility seriously; it is not an abstraction for us. It is the reason we come to work. The patients living with Alzheimer's disease, Rett syndrome, and Fragile X syndrome deserve a company that is focused, honest, and relentless, and that is what I intend to deliver.

In closing, we appreciate all participants taking the time to listen in on our call today. We will be speaking to the market again on our 2026 fiscal fourth-quarter and year-end earnings call in November. Here, we will provide a more comprehensive update on our progress and go into more detail on future milestones. In the meantime, we will update the market with any material progress via press releases.

Please do not hesitate to contact our Investor Relations team with any questions, comments, or concerns. They are received, read, and reviewed. Thank you.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

Good morning, everyone, and welcome to the Anavex Life Sciences Fiscal 2026 First Quarter Conference Call. My name is Clint Tomlinson. I will be your host for today's call. [Operator Instructions]. 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 and this includes, 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 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 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 U.S. to advance blarcamesine as a potential new treatment option for patients.

We recently announced Anavex 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 the feedback to Anavex development plans. The meeting discussed the potential path to support blarcamesine for Alzheimer's disease. In order to move forward, it is expected that existing data from the Phase II B/3-[indiscernible] program will be submitted to the FDA.

In December, as expected, the CB adopted a negative opinion on the marketing authorization application for blarcamesine. Subsequently, on December 18, Anavex 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 cooperator. In November, we announced presentations at the 18 CTAD conference in San Diego. The oral late-breaking communication oral blarcamesine Phase IIb/III trial confirms identified precision medicine patient population, significant broad clinical and quality of life improvements for early Alzheimer's disease patients and to poster presentations featuring by blarcamesine.

Going 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 16 Intrinsyc capacity friailty and Sarcopenia Research Conference for healthy longevity to be held Mark 10 to 12 at Johns Hopkins University, Bloomberg Center in Washington, D.C. New findings on a clinical relationship with a biomarker correlation between clinical endpoints and reduce brain region atrophy with blarcamesine in early Alzheimer's disease. A publication on Alzheimer's disease regarding precision medicine, AB clear public populations of the Anavex 2738D004 Phase IIb/III 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, which has the potential to establish effective treatment of early Alzheimer's disease through 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 noncash working capital accounts.

As of today, we anticipate that at the current cash utilization rate, our cash runway is more than 3 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 at 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.

Thank you, Sandra. In summary, we are focused on continuing to advance the development of our precision medicine compound. We 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, Chris. [Operator Instructions]. And our first question will come from Raghuram Selvaraju from H.C. Wainright. .

Hello, can you hear me? .

Yes.

Firstly, I was wondering if you could, at this juncture, provide us with some additional information regarding who the Rapiter and co-rapporter are for the reexamination of the CHMP opinion on blarcamesine.

The 27 countries of the EU decide on to rapporteurs. It is 1 of the 2 countries of the 27 will be the rapporteurs.

Okay. Can you provide us with additional information regarding the time line with which the reexamination nation is likely to occur. My understanding is that in effect, it starts a new clock, but this might be as short as 6 months. Can you confirm that?

That is correct. It is a 60 plus 60-day period where we respond to the reexamination request and then the review by the 2 rapporteurs will take another 60 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 time line 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 giving that we will provide the full data package to the FDA for addressing their review and expecting next step from there.

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

There was a Type C meeting.

Next question comes from Tom Bishop of BI Research.

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, brain volume data, all 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 that there is a requirement for granting conditional approval for if the disease is serious, if there's a major unmet need, if the data shows clinically meaningful effect, if there's a strong mechanistic rationale, especially linking genetic variants and it is supporting evidence from translational data available. And the sponsor is then also committing to a study in executing it and confirming the efficacy during the approval -- during the approved process. .

And we are including the data of the AD004 study, the open-label open label study, the data on the [indiscernible] 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 -- those last few that you mentioned in the original submission such that this could potentially be more persuasive as it is for me.

Yes. 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 with drugs, which were prior approved already and with very large companies submitting those trial data were 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 how to repackage or rearticulate the strength of the package or of the data.

And with the FDA, I know the question was asked when might you file the state with the FDA. I mean it kind of already exists. So I was just wondering if you can be any more clear about why they can't -- why you can't get that data to the FDA very soon.

It's in process. And you to understand the FDA has a certain meeting request, which require 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. So 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 to see you 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 3 countries in 3 continents, in Canada, in U.K., 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 [indiscernible] trial, which we -- I mentioned before.

Okay. Well, is the -- it's been a little while since the Rett trial was finished. The Parkinson's trial was finished several years now, and I was just wondering if you can give us any near-term time line for some of these schizophrenia just wrapped up the first trial as to when we'll get something in this clinic.

Yes. Absolutely good question. We also plan a schizophrenia program to continue, as I mentioned this morning. So we are really going to 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 disease trial. .

The next question will come from Jesse Silveira from Spirit of the Coast analytics. .

This is Jesse Silveira with Spirit of the Cost Analytics. 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 the blarcamesine works better for patients with sigma-1 wild type. As a part of this 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. So this statement appears contrary to the facts because the drug is effective for patients who do not have a mutation, the sigma-1 gene also and as sigma-1 wild-type. So is it the company's opinion that the CHMP made an error and how they phrased their rejection? Or can you clarify the company's understanding of this statement in particular?

We would not criticize the regulatory bodies, but we would say that in consistency with our interpretation of the trial, we met the ADAS-Cog13, and there was more significant in the wild-type sigma-1 population as well as in the sealant boxes, which also was superior to the 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 48 weeks in an early Alzheimer's disease 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 population, you will see, and we submitted that for publication, it's already publicly available in a preprint that the ABCI population, which includes sigma-1 wild type carriers with the color Gen241 wild-type gene that those for patients have significance, reach significance across the board.

So for ADAS-Cog13, for our ADC ADL and for CDR sum of the boxes. And they're not only us achieving significance but they also achieved this with high clinically meaningful effect sizes, which are sometimes 2 to 3x larger than what we have seen so far from other compounds in the pipeline or on the market. So that's kind like why this is intriguing now to also point that out and have that discussion and put that forward.

Okay. And I'm going to skip around a minute just because you kind of led into it. So you stated in your [ Barrow ] 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 that interview, you explained the ADCS-ADL 1 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-Cog13 and CDR sum of 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?

Yes, as I just stated, this is exactly the discussion which is probably ongoing. If this ADL is identified clearly is not valid anymore and if you follow science, you would agree with that because it's an endpoint which has been earmarked as being useful for a word, Alzheimer, for moderate and severe optima, but not sensitive enough for the early Alzheimer's 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 make that argument as well.

Okay. And with that said, you went over the 60-plus 60-day time line earlier for this revaluation. We should be, I believe, near 60 days now. Have you already submitted the new strategy and package to the 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 SAG will be part of the review process since we requested that, and we will expect this to be given to us, dialogue involving the SAG, Scientific Advisory Group from the EMA for from the neurologic neurology team. .

Okay. And if I have it correct, you have committed to running a confirmatory Phase IV trial, if approved for CMA using paying patients as a real-world cohort. 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 IV trial with these patients? Or how will with that look, I guess?

Yes, we would run the trial as the regulatory body the CGM 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 28 January 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 the EU moving away from [indiscernible] in favor of defense and economy. So in light of these statements, it's our understanding that Anavex is to participate in Access AE funded by the European Commission. Can you please give more blarcamesine, a currently unapproved drug is to be involved in this program? Like is the company running this trial? What are end points and objectives of this trial? When will the first patient be dosed or anything else you'd like to offer?

The Access ID 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 specific carve-out or not carve-out, especially part of this very large brand, if you like, is a dedicated clinical trial of blarcamesine is 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 a 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 AXIS 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 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 in early Alzheimer's patients? Or is this is there like a preventative component to this trial?

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

Okay. And this would be considered AD006 on your pipeline chart. Is that correct?

That's correct, yes. That's AD006.

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.

Yes, so we have submitted now 3 papers, which 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 the soundly claim safety and efficacy of the drug on cognition, objective brain atrophy markers and not to mention patient-assessed improvements measured by the quality of life AD survey. Yes. So we have no further questions, and thank you again for having us.

We appreciate that. Thank you.

Thank you, Jesse. 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 are we 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 afternoon, and welcome, everyone. I'm Colette van Buchem, an associate at JPMorgan on the health care team in New York. Today, it's my pleasure to introduce Anavex Life Sciences. With me on stage, we have Christopher Missling, President and CEO. Christopher, I'll pass it over to you. Thank you.

I appreciate the very kind introduction and an invitation to the JPMorgan conference. Let me introduce Anavex Life Sciences. Since we are a public company, I'd like you to read this.

I learned from a successful oncology research, which I was involved before prior to Anavex that one important lesson. The power of the body to fight cancer by activating the body on defense mechanism. That led to the question, why wouldn't that be possible with CNS diseases, which consist of even more complex pathologies. Here at Anavex, we like to change things. We like to move science forward. We are dedicated to therapeutics, discovery and development of targeted central nervous systems treatment.

Instead of trying to fix already broken things happening downstream within the neuron, we try to fix wrong things at the start, at the upstream, at the reaction cascade or processes. The way to address complex diseases especially in Alzheimer's disease, is transforming brain health to patient-oriented personalized medicine. And the company's lead asset, blarcamesine is a once-daily oral small molecule that enhances our autophagy through sigma-1 activation and restore cellular homeostasis.

Impaired autophagy processes are upstream of both a beta and tau and therefore anticipate the neurodegenerative process in Alzheimer's disease. We believe the way that we are well positioned to expand on the transformative precision medicine platform and capitalize on significant market opportunities.

So let me share this market opportunity with you. The aging is correlated Alzheimer's, and the worldwide dementia cases are projected to reach 130 million people by 2050. This data was recently received by Alzheimer's Association and is addressing a growing burden with convenient oral once-daily blarcamesine or commercially scalable potential medicine like blarcamesine might be the way to address this growing market.

I'd like to share with you the data which indicated, which was published recently that blarcamesine in its Phase II/III study demonstrated significant slowing of patient relevant cognitive decline in the Phase IIb/III trial. We demonstrated in 48 weeks a 36.3% and benefit and in the prespecified patient population was up to 49.8% at 48 weeks with the primary cognitive endpoint ADAS-Cog13.

We also demonstrated a very solid safety profile with no associated neuroimaging adverse events, and we observed no deaths in the trial, and that extended also to the open-label extension study. In addition to that, 2 very strong biomarkers of the pathology, one is the brain volume loss, which is the correlation of the disease or also called atrophy was significantly slowed with the active arm blarcamesine. In addition to that, the classical biomarker of the pathology measured by a beta 42 plasma ratio was significant as well.

When we did a survey and it was also a published survey we looked up, it sounds intuitive, but there's a very high preference from patients and caregivers to request an oral dosage form for disease-modifying drugs for treating Alzheimer's disease. And also, the explanation for that, these patients are impaired and have a high propensity of not wanting to leave their house or their home, their family environment because they already are in a situation of impairment and it will make it even worse.

We also hear a lot of patients telling us that one of the key features why they appreciate much more an oral solution for Alzheimer's treatment is because every moment when they can stay with the families together or with their cared -- with their loved one is so much more value compared to being taken out to a hospital where they have to undergo a PET scan or an MRI review.

In summary, I'd like to point out that blarcamesine offers this opportunity as a convenient once-daily oral treatment. And we have demonstrated in our programs a significant improvement over comparable currently available clinical outcomes both from a safety as well as efficacy point of view. We also have a financial comfortable situation of having over 3 years of cash without debt on our balance sheet. And we have a very solid IP protection reaching for our market product candidates up to 2040. But more importantly, we are in currently discussions with regulatory agency in key markets in progress with the objective to determine the potential pathways to obtain marketing authorization for blarcamesine.

We are not only sitting on blarcamesine for Alzheimer's disease. We also have a broader portfolio, encompassing other indications with high unmet medical need. One of them is, in addition to Alzheimer's, Parkinson's disease. We already completed a Phase II study in Parkinson's disease dementia, and we are proceeding now this year with a larger Parkinson's disease trial.

We also have expanded blarcamesine's potential in a rare disease setting, specifically Rett syndrome, which we will continue with. But also, we're expanding this year a study in other rare disease, which is much larger than Rett syndrome, which is Fragile X syndrome, which is the biggest part of the autism spectrum disorder. And we're planning a study this year, more about later. But we also have other indications infantile spasm and Angelman syndrome, where we have very solid preclinical data and we could advance it as well.

But last but not least, I also want to point out, we have an expanded portfolio with another drug called ANAVEX 3-71, which is also an orally medication -- potential medication. And we just completed recently a Phase II study in schizophrenia with solid data in Phase II, and we're planning to advance that indication in this program as well. And we have also orphan designation for frontotemporal dementia and very solid preclinical data with ANAVEX 3-71 in Alzheimer's disease.

Again, in summary, an oral convenient treatment options have a strong potential to be more cost efficient, especially in this DNA of looking for reducing costs for the entire Medicare system and a global health care system while biologics have not only the higher cost burden but also potential safety concerns.

We believe we are well positioned to access this economic value with our progressing pipeline and multiple milestones are in reach towards potential commercialization. More about this in due course.

One of the key features of the mechanism of blarcamesine as well as ANAVEX 3-71 is the restoration of autophagy. And autophagy is an important feature, which is an upstream tangential degenerative approach in the biology of nature, which does not start with a pathology itself but degrades over time. So while we age in this procedure of health path, we are seeing a degeneration or a decline of autophagy activity.

But this autophagy is essential for CNS because CNS molecules neurons cannot get rid of their trash or their -- what have the -- it has to be discarded. It has to be recycled, and that process is called autophagy. And this cleanup mechanism diminishes with aging. And we have the fortunate situation, we're able to confirm in vivo and in animals that all blarcamesine acts at a clear reactivator of this neural impaired autophagy. And that gives us a chance to also point out, in addition to that, that the cellular stress, which is also increasing while autophagy is decreasing, that one of the key features of blarcamesine or our drugs is to reduce cellular stress. So it's really 2 converging features of the pathway, which are countering the aging process in the pathological process correlated with aging.

I'd like to now share at this point a bit more about our pathway to advancing autophagy platform. I mentioned we have regulatory interaction. The most advanced is right now with EMA, and we are in the process of getting reexamination of the blarcamesine for Alzheimer's disease in Europe through the EMA, and this will take place and will start in the first quarter of this year. It's starting sooner than in the first quarter, but it will take place in this period of time.

We also have been fortunate enough to be part of a larger European EU-funded consortium, which includes blarcamesine in a predictive study of once daily oral blarcamesine in Alzheimer's disease.

I mentioned we are planning a Parkinson's disease study, a larger study, which will be larger than 6 months. And we're also planning to study -- start a study in Fragile X, the largest indication of autism spectrum disorder of genetically identified autism spectrum disorder, where we found a very strong biomarker of EG, which has been now submitted for publication, which correlates with the pathology in humans and in animals. So this paper describes the EG biomarker in animals, which, however, is also confirmed in humans. So this is a very important part of the clinical study to add a strong biomarker of pathology to the clinical trial.

And last but not least, we're also expecting several publications. Among them, the precision medicine, ABCLEAR publication for automate disease with blarcamesine, which was submitted as well as a publication of Collagen 24A1, which is demonstrated to be instrumental also the wild-type gene for response of blarcamesine in Alzheimer's patients and more about that soon.

So let me now share with you more about the Phase IIb/III, and let me start with the mechanism of blarcamesine. One of the key features of autophagy of the Alzheimer's pathology is to identify the true causality, which probably is closer to the true origination of this complex disease. And we hear often that a beta or tau's [indiscernible] start or defined pathology. That's actually not entirely the case because impaired autophagy has been now identified precedes these beta and tau aggregations, which then lead to neurodegeneration.

And it's really important to differentiate between the quality of a biomarker of pathology and the potential target of a disease. So we are completely in sync and understand and believe that very good biomarkers are concerning a beta and tau are very valuable, and we integrate them and have integrated them in our clinical trials and will continue to do so. But we believe that the closer to the origin of the pathology is more likely the autophagy impairment, which precedes that. In order to confirm that we were able to identify with the help of third-party scientists in in vivo and in vitro, the exact pathway blarcamesine reactivates impaired autophagy. And that is very important to appreciate because it's relatively complex. I want to run you through this slide.

So when autophagy is impaired, that means that circle, that half circle does not close out in a full circle to build the lysosome. And that's often because of either lack of certain key autophagy proteins like LC3 or other reasons, they cannot form this. We are able to demonstrate that sigma-1 activation through blarcamesine in combination with another protein of autophagy called GABARAP are forming a synergistic aggregate, which then is able to move forward the autophazone into a functional and fully bioactive lysosome. And that has been demonstrated in this publication quoted on the slide below. So it's really important to appreciate that we exactly understand how blarcamesine is able to restore and switch on the autophagy, which is impaired by bringing in or sending in sigma-1 activation through blarcamesine presence.

And another very important feature of pathology is the observation that the brain shrinks with the progression of the disease. And not only does the brain shrink, but also the holes in the brain called lateral ventricles, they are enlarging, which you can see nicely in this picture. And we demonstrated very nicely dose dependently also that in our Phase IIb/III study, blarcamesine was able to reduce or retain the brain volume, reduce the brain volume loss or retain the brain volume consistent with the normal brain function. And that was demonstrated in the whole brain in total gray matter in parietal lobe, in temporal lobe, limbic lobe, insular cortex and frontal lobe, very important regions of the brain correlated with function and cognition of a patient.

So a significant correlation not only with the downstream pathology or some scientists refer to this as the N in the ATN spectrum. A standing for a beta, T for tau, N for neurodegeneration. So the shrinking of the brain is -- represents neurodegeneration. So we're able to show that we're able to stop and halt the neurodegeneration of a patient with blarcamesine.

And if I now switch over to the clinical data of blarcamesine, you will appreciate what you see in a minute that since we activate with blarcamesine, sigma-1 proteins, which is underexpressed in the pathology compared to healthy brains. So study in healthy brain show a high -- very high expression of sigma-1 protein, while patients with Alzheimer show a very low expression with a PET scan of sigma-1.

We're able to demonstrate that in our trial, the patients with carried the sigma-1 wild-type gene, which is represented by around about 70%, 7-0, of the population also are able to demonstrate a stronger signal of response of clinical response to the drug to blarcamesine compared to their respective genetic mutations, which are simple missense variant, which does not indicate by the way, to be more likely getting Alzheimer or being impaired in their life or getting any other diseases. So it's not like ApoE4, which is a risk gene. The 1-point mutation sigma-1 is a complete random mutation, which has no impact on quality of life or such. It's just an ability to demonstrate the fidelity of the signal of blarcamesine in the clinical trial. So if you like, you can point out this is another biomarker of showing the fidelity of the signal.

But it's important to notice that the signal for the clinical outcomes are very clinically meaningful, both in the ITT and in the prespecified sigma-1 wild-type population, both for clinical endpoints, ADAS-Cog13 and CDR sum of the boxes. And it's important also to point out that this consistent safety profile was confirmed also in the long-term extension study over 4 years. And the titration was able to reduce one of the major adverse events observed in this trial, which was dizziness and demonstrating that this adverse event is a manageable adverse event.

And we also want to point out regarding safety, we did not observe any associated neuroimaging events and no deaths were observed in the trial duration caused by the study drug. So again, summarizing that the clinically meaningfulness of this study was confirmed with precision medicine and validating the mechanism of action.

In the long-term extension study, which I was referring to, we demonstrated in a comparison to a natural history study, which has been used quite often recently also by other companies, the ADNI control group, and we demonstrate over a period of 144 weeks, a very resilient, strong holding up and not declining as compared to standard of care as demonstrated in the ADNI study with clinically meaningful outcomes over time. And this data allows you to calculate the time saved of a patient. And that's what is a measure with patients appreciate much more because they don't understand what ADAS-Cog13 boxes is, but they understand very well the expression time saved. How long will you stay with your families or with your loved ones without any decline of your function or capabilities.

This patient relevant outcome was identified or calculated to be -- to reach up to 18 months so that is the period of time which a patient will be provided sustained patient benefit by maintaining functionality and independence based on this ADNI comparison -- ADNI study. And this in totality, of course, is relevant for a patient and extends the dignity of aging in these patients.

I described the impact of autophagy decline over time. And the question was what would we -- what would happen if we interact earlier in the pathology of the disease before the pathology even starts. So what if we do a test of pretreating the -- in this case, we did animals first before doing this with patients. If we pretreat with blarcamesine animals, which are healthy and then make them sick with a beta injection or tau or other features, and we then observe what happens to these animals in a cognitive and functional state.

And we observed that animals who received blarcamesine preventative for 7 to 10 days never developed cognitive impairment measured by the water maze, while those who did not get the treatment but got placebo instead, they developed the expected cognitive impairment in the water maze, and this was published recently. So it confirms that this continuum of autophagy impairment does not have to start when the pathology is already present, but you can also think of this as a prevention of prophylactic effect of blarcamesine potentially going forward. Of course, it has to be confirmed in humans to claim that in humans as well.

Now let me switch gears and share with you what we refer to moving now into precision medicine in Alzheimer's disease. And this is important because it is also the way the future of clinical treatment has been demonstrated, taking the playbook from oncology, which I mentioned at the beginning, where precision medicine or patient-oriented treatments are today the standard of care.

And our ambition is to find new precision medicine approaches, which approximate the normal cognitive decline as observed in healthy aging adults, which also demonstrate a decline, by the way, nobody stays cognitively perfect over time while they're aging. And we have to really factor in the reason for looking into this is heterogenesity of the disease, the complexity requires to look more into detail how is the -- these patients constituted in order to find better response to patients than what we have found today.

And we identify a strong effect with the wild-type sigma-1 population already, the 70%, which I showed you with you and which also is consistent the mechanism of action and specific to blarcamesine to restore functionality and cognition.

But now I will share with you, in addition to the sigma-1, another gene, in combination, which gives us the following data. And the data you see here is a chart of the blue line of blarcamesine treatment from our Phase II/III trial in combination of the wild-type sigma-1 with the Collagen 24A1 wild-type cohort. So 2 wild-type cohorts, which both individually represents around about 70%, 7-0, of the entire population, both when you look at gene databases as well as in our trial, consistent with our trial. And the orange line is a comparison of a -- publication comparison of barely detectable prodromal Alzheimer's patients decline. So patients who are not cognitively impaired. And you see they are matching the trajectory while the gray line is the placebo standard of care arm of our study Phase IIb/III.

And what you see that in this cohort, the 30-milligram cohort, which was the most homogeneous cohort of the trial shows a similar referenced to the outcome to the reference barely detectable prodromal decline. And that is even strong -- to be considered to be more impactful, the Alzheimer effect because the baseline, which is not shown here, is much -- the Alzheimer progressed baseline of the blarcamesine cohort was more advanced the prodromal patient cohort, non-patient but healthy cohort.

And if you calculate now the difference between the effect of the drug blarcamesine to the placebo, it results in 84.7% clinical benefit for patients compared to placebo. And that is really moving the needle towards normal aging profiles. And that's extremely powerful point to make to a physician and to a family that if you take this drug, you potentially would become able to retain your function for much longer and an extremely high level.

And the unprecedented blarcamesine effect is demonstrated in this chart. And you can see now the green box pointing out in this cohort, which is again between 50% to 70%. And the strongest was a homogeneous cohort of 30 milligram in this arm, reaching significant effects for ADAS-Cog13 of minus 4.7, highly significant and the 84.7% improvement as well as the CDR sum of the boxes, it was minus 1.4 points and also highly significant, reaching 75.2% in difference to placebo. So extremely meaningful and also real impactful effect sizes for patients with an oral once-daily treatment potential.

I also want to point out one of the key features we have heard also in regulatory review discussion was what is the benefit to the patient? And one scale we covered in our Phase II/III trial was actually the quality of life AD scale, which is the patient-oriented benefit scale, which measures the self-assessed quality of life of the individual Alzheimer's patient.

And in this measure, you go through a question list what the patient will be asked, physical health, overall physical well-being. Energy, a level of energy and vitality. Mood, emotional state of feelings. Living situation, satisfaction with where the person lives. Memory, cognitive function and memory abilities. Family, quality of relationship with family members. Marriage, significant other, satisfaction with the relationship or partner. Friends, quality of social relationship with friends. Self, ability to do chores, ability to do things with fun, enjoyment and leisure activities. Money, financial well-being. Life as a whole. So really very detailed measures of quality of life.

And in the next slide, you will see the outcome of this scale in totality. You see already a trending in the ITT population as in the active [indiscernible] versus placebo. But in the quality of life measures for the respective genetic groups I defined ABCLEAR3, especially, you see a significant improvement over a placebo, but not only that, but it was above baseline when they tried -- when they start the trial. So the quality of life for these patients is not only sustained, but it's actually net improved with blarcamesine after treatment period of 48 weeks. And that's what really measure -- is a measure relevant for patients.

So going into what is relevant for patients, I want to touch upon the convenience for the patients, families and also for the physicians. So let me share with you that one of the key advantages of blarcamesine is that it allows direct access for the patient to a new oral treatment because he just goes to the doctor and gets the prescription. So the focus stays on the individual patient. He's not being pulled into all directions and has to go to MRI centers or PET centers, which, as I mentioned before we heard, he doesn't like to do.

The advantage for the family is also there's less stress for the caregivers and the families. There's no financial strain involved. They don't have to take off time to ship them or send them or drive them to a PET center or an MRI center or infusion center, as a matter of fact. That means there's no impact on the own workforce schedule for the family.

And last but not least, also the physician benefits from that because he keeps his streamlined workflow. He doesn't have to become a project manager for orchestrating PET scans, MRI in another place and so whatnot. So the simplified patient access or care with all therapy means no PET, no MRI needed, no lumbar punctured really what patients and families and physicians are looking for.

And in order to complete the picture of the large patient-oriented identified accessible opportunities, I want to mention with you that -- to you that we have been in close contact now with advocacy groups, with patients and around the globe, and they all tell us the same thing. There's such a demand for a simplified solution with an oral effective drug, which is safe, which can be given, which can be shipped to the Midwest, which can be given without limitations to areas of limited access and knowledge. So all of this is an ongoing education, which we will also continue in order to help our community to drive and build resilience and health ability to have -- offer potential actionable solutions.

I'd like to also mention the addressable market, which we are covering with our portfolio is not limited to Alzheimer's. We talked about Alzheimer's a lot today, but there's also a large unmet need in Parkinson's disease and schizophrenia, I mentioned, which I mentioned, and also Fragile X, which is 6x the size of Rett syndrome. And as I mentioned, we're progressing that as well. And as a reminder, we have good IP protection in the global markets of relevance up to 2040.

I also want to touch upon briefly on the financial background. We have right now in the last reported cash position around about $120 million. With our current cash utilization, we're expecting to be comfortable with more than 3 years with that. And we also have, in addition to that, no debt, which we have to service.

And we also like to point out this fiscal responsible proceeding is also thanks to nondilutive funding, which I'd like to thank for the International Rett Syndrome Foundation, especially also the Michael Fox Foundation. So we continue also to keep this conservative approach fiscal responsibly going forward.

And in summary, I'd like to again summarize, we focus on patient-oriented brain medicine. We address large-stage Alzheimer's program, a huge significant unmet need with a scalable commercial opportunity. And the emerging body of clinical data with blarcamesine suggests a very high efficacy in genetically defined large Alzheimer's population through precision medicine. And autophagy platform, which we represent in our portfolio offers an opportunity through expansion into broader CNS space as well. We have a strong financial position, and we believe we have long-term IP protection secured. And we also expected key near-term milestone.

With that, I'd like to thank you, and we're open to questions. Thank you.

Thank you very much for the very informative presentation, Christopher. We'll open the floor for any questions that the audience may have. Otherwise, I have a few to ask. Could you briefly explain and outline the sigma-1 activation mechanism underlying blarcamesine and explain why it plays such a central role in your therapeutic approach?

Very good question. So blarcamesine mode of action was confirmed in several peer-reviewed publications. Blarcamesine is an activator of in vivo agonist and the confirmation of that was established in a PET study. So it was also published, demonstrating dose-dependent sigma-1 receptor engagement. Sigma-1 is an integral membrane protein involved in restoration of cellular homeostasis. It activates an upstream compensatory process and autophagy through sigma-1 activation.

Sigma-1 receptors are significantly lower expressed in patients where the brain is not functional anymore compared to healthy normal brains. And hence, activation with a selective sigma-1 agonist helps like blarcamesine could restore the compensatory upstream process of autophagy through sigma-1 activation.

Great. I have another question. How does Anavex plan to position blarcamesine from a commercial standpoint?

So a recent high-profile Alzheimer's disease trial failure of the GLP-1 agonist demonstrated that Alzheimer's disease is a very complex disease. In addition to that, we also saw a failure of a -- failure in an anti-tau program recently by J&J, for example. And it shows that while these are downstream approaches, we are thinking that more upstream restoring autophagy through sigma-1 receptor might become or more related and closer to the pathology of Alzheimer's disease, which is very complex. And this gives the aging population potentially a solution which they're still demanding and waiting for potentially safe and accessible approach, which is given the unmet need and the safe accessible medicine would be something which we would make sure we don't delay too long for having patients access to such a potential solution.

Great. Any other -- great -- the microphone will come to you.

I just had a question I want to understand. So does this mean that you have to treat presymptomatic patients?

No. We trialed in our Phase IIb/III trial early Alzheimer patients. Early Alzheimer's is defined by MMSE baseline score from 20 to 28. It's also the same population the 2 antibodies were treated. And we also preceded the Phase IIb/III study with a Phase IIa study, which had mild-to-moderate patients. So we have been demonstrated to be able to address or give patients benefit in the mild to moderate and the stronger data, of course, with the larger trial in early Alzheimer's. And that's also the defined population in the regulatory discussion.

Any other questions from the audience? Then I want to thank you once again, Christopher, for the presentation.

Thank you very much.

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. Please note that this conference is being recorded, and the call will be available for replay 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 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 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, 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 Dr. Missling.

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 blarcamesine and oral Anavex 371 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 blarcamesine 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's disease community. The EMA 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 in 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 of a clinical trials documents, facilities, records and other resources to ensure compliance with GCP guidelines. We're looking forward to working closely with EMA and other stakeholders to advance our investigational therapy for early Alzheimer's disease.

Importantly, we also announced that we had initial contact with the authorities in the U.S. 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 blarcamesine in other indications, such as Parkinson's disease, Red syndrome and Federal ex.

This will include the disclosure of planned future clinical trial designs as we continue to advance our therapeutic pipeline. During the most recent quarter, we announced several new scientific and medical publications, which includes a peer-reviewed publication in the Journal Neuroscience letter title Prevention of memory impairment in hippocampal injury with blarcamesine in an ultimate disease model.

This study shows that pretreatment with blarcamesine prevented amyloid better induced memory impairment and brain oxidative injury suggesting that blarcamesine is an attractive candidate for Alzheimer's disease pharmacological prevention. AP reviewed publication in the Journal iScience, ascertaining the precise autophagy mechanism of Sigma-1 receptor through [indiscernible] activation titled conserved LIR specific interaction of Sigma-1 receptor in GABA RAP.

A publication oral blacarbisine Phase IIb/III trial confirms identified precision medicine patient population significant broad clinical and quality of life improvements for early Alzheimer's disease patients to be available online as a preprint and in submission to a peer-reviewed medical journal.

Anavex announced the latest published transitic results for blarcamesine on all standard scales for measuring Alzheimer's disease and cognitive decline after 48 weeks. The defined precision medicine population, ABCR, consisting of early Alzheimer's patients with confirmed and progressed pathology taking 30-milligram once daily oral blarcamesine 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 blarcamesine, this new data demonstrated continued long-term benefit from oral blarcamesine compared to decline observed in the Alzheimer's Disease Neuroimaging Initiative control group also called ADNE, 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 [indiscernible] participants compared to the AgniControl Group at 48 weeks, with a significant and clinically meaningful difference in mean change from baseline [indiscernible] total score of minus 2.68 points.

Over the course of the open-label extension study at [indiscernible] 96 weeks, these 2 groups further diverged sharply with statistical significant differences in mean change in ADAS-Cog 13 total score at 96 weeks of minus 6.41 points. The difference between groups continues to increase at 144 weeks to ADAS-Cog13 total score difference of minus 12.78 points.

The results provide evidence of the significant beneficial therapeutic effect of blarcamesine, which positively separates from -- which positively separates from the ADNE control group with duration of treatment. This significant beneficial therapeutic effect of blarcamesine compared to decline observed in the ADNE Control Group, translates into 17.8 months of time saved with oral blarcamesine, allowing for long independence of the patients by approximately over 1.5 years.

Looking ahead, Anavex will be presenting additional data and scientific findings at upcoming conferences and in publications. These include the direct relationship between [indiscernible] function and reduced brain region atrophy with blarcamesine. Oral blarcamesine for early symptomatic Alzheimer's robust effect size through precision medicine and analysis of the ANAVEX 2-73-AD-004 randomized trial.

Also, newly identified precision medicine gene collagen 24A1 with over 70% prevalence, which establishes effective treatment of early Alzheimer's disease with blarcamesine. And also continued long-term benefit from oral blarcamesine compared to delayed start analysis and decline compared to natural history studies.

With regard to ANAVEX 3-71, in October, Anavex announced positive top line results from its placebo-controlled Phase II clinical study evaluating ANAVEX 3-71 for the treatment of schizophrenia in adults on stable antipsychotic medication. The study successfully achieved its primary end point demonstrating that ANAVEX 3-71 was safe and well tolerated.

The safety profile was consistent with previous studies of ANAVEX 3-71 in healthy volunteers, with no serious 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 3-71 represents here for a transformative opportunity in neuropsychiatric drug development. Leveraging its unique dual Sigma-1 agonist, M1 PAM mechanism to address multiple high-value indications through a unified neuroinflammatory biomarker platform, further detailed analysis of randomized strictly double-blind placebo controlled clinical trial ANAVEX 3-71[indiscernible] revealed very encouraging data in patients suffering from schizophrenia.

Following successful Phase II results from the Z001 study, while confirming the excellent safety profile of ANAVEX 3-71, the study demonstrated reduction in fab and wild 40 neuroinflammatory markets. GFAB is a structural protein of osteocytes in the brain represents a parent activation of osteocytes, the major brain [indiscernible] cell lineage.

Astrocytes participate in brain neural function in multiple ways. Amongst them, critical modulation of synaptic relay between neurons and neural circuits. It's dysfunction a key petrogenesis mechanism in schizophrenia. This positions ANAVEX 3-71 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.

In addition to schizophrenia, one high unmet need opportunity would be depression in Alzheimer disease with currently no approved therapies. Up to 40% of people with Alzheimer experience significant depression, especially in early and middle stages of the disease. Depression in Alzheimer is associated with worse quality of life, accelerated cognitive decline and earlier onset of dementia symptoms.

The neuro inflammatory biomarker strategy positions ANAVEX 3-71 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 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 at September 30 was $102.6 million, and we had no debt. During the quarter, we utilized cash and cash equivalents of $8.6 million in our operating activities after taking into account changes in noncash working capital accounts.

As of today, with the current cash balance of over $120 million, we anticipate that at the current cash utilization rate, our cash runway is more than 3 years. Our research and development expenses for the quarter were $7.3 million, as compared to $11.6 million in the comparable quarter of last year.

General and administrative expenses were $3.5 million as compared to $2.7 million for the comparable quarter of last year. Compared to the same quarter of fiscal 2024, we saw a decrease in operating expenses, mostly driven by the completion of a large manufacturing campaign of blarcamesine and a decrease in clinical trial activities as a result of the completion of our open-label extension studies and our ANAVEX 3-71 Phase II study in schizophrenia.

And lastly, we reported a net loss of $9.8 million 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&A.

Thank you, Christopher. [Operator Instructions] It looks like our first question will come from Michael Oba day from H.C. Wainright.

So I'll be acting the question on behalf of Ram Selvaraju from right. I 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 -- on the outlook for [indiscernible] in Alzheimer's disease.

The second 1 is the next form of discussion of [indiscernible] to take place inn FDA?

And the third question is, what initiatives does Anavex plan near term to pursue [indiscernible] approval in regions beyond the European Union and the United States?

I appreciate the questions. So to answer the first question about the impact of the semaglutide results. We understand there's an unmet medical need here. And this is certainly further highlighted by the recent setback by the 2 VOC 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 Evoke semaglutide GLP-1 finding, highlight the complexity of Alzheimer's disease biology and the challenges of expecting the metabolic pathway alone to meaningfully alter the new [indiscernible] processes. But Alzheimer is more complex, involves impaired proteostasis, optophogy dysfunction, synaptic failure and 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 [indiscernible] amine with this upstream mechanism of action, which restores Aptophagy, which precedes these pathologies I just summarized and has demonstrated in early Alzheimer's disease patients, clinically meaningful efficacy of slowing [indiscernible] declined significant amounts, in some cases, over 50% with an acceptable safety profile with no area and as demonstrated in the Phase IIb [indiscernible] study.

So the answer to the question is this makes it more clear that this is a complex disease and is a lack of compounds near term available for patients to address this unmet need.

Second question is about timing. So we provide, as we stated, updates what will follow up in the initial discussion with the U.S. regulators, and we'll provide updates as we receive them. But we're very excited about the initiation of these discussions.

Regarding the third question, 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. Thank you very much for the clarity and transparency.

Thank you.

The next question is going to come from Tom Bishop of BI Research.

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

So 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 bolts down to demonstrating to the 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 to make the glass has full that digital correlation or information about objective biomarker, which are not subject to influence might be helping and getting to that point. So that is the background of biomarkers -- including biomarker assessments.

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

We have communicated, and it's been published that we have a very strong biomarker of the pathology, which is the analogy of oncology with 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.

And the same is in Alzheimer's disease is the brain shrinks. So the brain gets smaller and 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 blarcamesine, while in the placebo arm this shrinking of the brain continues. -- which is the clear definition of the advancement of the Alzheimer otology.

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 48% to 86% slowing depending on the gene biomarker or a combination. Was this -- I guess, this was not considered by the CHPT as it came out MP because it came out kind of late. But can this be included for consideration on reexamination?

So 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, but also clinically meaningful effect in both cognitive and functional, but also in all the other end points consistent improvement and significant improvement of the clinical outcomes that is the CGI that is the quality of life and PIQ, MMIC all the measures are Scok13, [indiscernible] on the boxes, ADCS-ADL.

In all this AB CLEAR 2 and 3 populations, we see clearly clinically meaningful and significant improvement. So we would like to also point that out, and that is really a good data set to have and to put this forward.

And also, last not 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 70% of the patients 7-0 in the trial. That means that quality of life is better after 1 year than at the start of the trial. And that's very impactful because that what is really impacts the individual patient.

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

It's really not -- it's really hard to speculate about this, but we would like to make sure we want to point out, we are motivated and driven by the fact that it's a huge significant unmet need for a drug with these features today, and we pointed out the recent pipeline failures.

And also, I want to point out that between '20 and '25 to this year and 2030, there will be more than $300 billion of large pharma revenue at risk from loss of exclusivity with over 40% of top pharma sales exposed, creating an estimated $90 billion 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 exploring your options if you get approval, for example, large pharma sales organizations and so forth to take blarcamesine to market.

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 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 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 do not see this drug approved because especially the ABC CLEAR data to me is so convincing that -- and the risks are so low and it's oral. 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?

Yes. as long as I'm still on, is there a mechanism of action for all '24 A1?

Yes, there is. And this will be now published in a peer review paper. But in summary, I can say that Collagen 24A1 is the ingredient -- key ingredient of the extracellular matrix called ACM. And when you look at pictures of brain, neurons or astrocytes, we see this very nice connections or network like a web spider web description or pictures.

And in the background, it's always like pitch black. And you were wondering this is how the brain looks like. And of course, it doesn't. It does not. And this background is actually the [indiscernible]. And that's where these neurons and ascites are sitting on in your brain.

And if you have a mutation of this exacolular matrix, then your response to blarcamesine is impaired. The autophagy flags the [indiscernible], which is the recycling mechanism of the neurons, which precedes a better and towel. 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 AADAS-Cog13 minus 4.7% in patients with that effect with that voltage and in the [indiscernible] boxes. The scores go up to 1.4%, minus 1.4%.

And these are really very unprecedented effects of benefit. And we pointed out that, that means that patients are actually almost not declining or declining less than prodromal patients, which are less impaired. So that's quite impactful. And so this is really intriguing science, and it will be published in a major peer-reviewed paper very soon. So extremely intriguing. And also [indiscernible] with the mechanism of [indiscernible].

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

I appreciate it. Thank you.

Thank you for the question, Tom. The next question is going to come from Jesse Silveira with Spirit of the Coast Analytics.

Can you hear me all right?

Yes, you're fine. Go ahead, Jesse.

This is Jessie Silvera [indiscernible] of the Coast Analytics. Some of these questions you've kind of addressed a little bit earlier, but hopefully, you can maybe provide some additional color on some of them. Yes, just to reiterate kind of one of your previous points.

So my first question is sort of an assumption though I think you got at 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 for negative CHMP trending or give details on the strategy going into the revaluation?

That's correct. That's correct.

Okay. Got that. And perhaps adjacent to that conversation, do you think you can give more detail on a statement that was found in the 14 November press release, it stated "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 the Alzheimer's disease community." I think it was Tom that was getting at this earlier, but -- can you comment any further on 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 or may not be presenting 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, by 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 analogies in Alzheimer, the clear pathological shrinking of the brain, which is one of the first features as Alzheimer himself actually identified in his patients with Alzheimer the first patient he assessed.

Subsequent later on, when he looked into the brain, he found this additional apparent features of proteins than identified as a better plug or [indiscernible]. But the first thing we identified was really 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 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 endpoint for demonstrating an objective effect of a drug, and that was demonstrated with [indiscernible]. So we just want to make sure that gets visibility. 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, going along with [indiscernible] treatment, but also the shrinking of the brain correlates with each patient with a improvement in the respective regions of the brain activities of the ADAS-Cog13 sub domains, for example, for example, learning and reading and writing is in one area of the brain.

And if that is improved in the clinical trial for the patient. And that same region of the brain responsible for that. If that also is less impaired in the active blarcamesine treatment arm compared to placebo. And if you can find this further confirms the true effect of the drug and that will be convincing in our opinion.

Yes. I think that's really interesting. I'm definitely looking forward to that. And I think kind of related in light of the magnitude failure is that they reported that the drug had improved biomarkers, amyloid and maybe [indiscernible] about tau. But 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 better cognition or whatever.

But moving along kind of on 9 September, the company PR really impressive at their 3 comparisons to prodromal populations. And had a detailed follow-on analysis of AD CLEAR 2 and [indiscernible] 3 subpopulations and a GWAS preprint a little bit later. ADA CLEAR 3 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 ABCLEAR1 versus ABCLEAR2 and ABCLEAR3? 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?

Yes. So the definition of ABCLEAR1, which basically is the wild-type Sigma-1 gene, which was identified already in the beneficial effect of that gene in the previous preceding Phase IIa study, which was published 2020, where we identified that patients with the SIGMAR1 wild-type represents 70%, 70% of the population had a better response to blarcamesine than those with a respective mutation. It's a point mutation, and that's how biology is of overall population, that's not patients, but overall population has a 1 point mutation, RS180866and this 1 mutation changes the confirmation of the gene makes it a little bit less viable or effective in its ability to restore homeostasis increase autopay, which is the mechanism of the activation of blarcamesine through SIGMAR1 activation its ultimate effect.

And so the patients with wild type, the fully functional non-mutated gene respond better. So this was identified in the Phase IIa. So we prespecified the analysis of the primary endpoint as well as the secondary and exploratory endpoints. With this in mind, how would patients do in the Phase IIb/III study with the wild-type SIGMAR1, and that was prespecified, and we now define this as ABCLEAR1. And we did indeed demonstrate or it was demonstrated that indeed, that was confirmed blarcamesine increased effect of patients with that of 70% run about this denim of patient 70, which improved better than the patients with the mutation. -- and that is improving.

So now ABCLEAR2 was the result of a preplanned in the trial. We did a whole genomic some analysis. That means we looked at all patients in the study and analyze their genes and gene 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 1 gene showing up as an extremely strong driver of efficacy in that gene turned out to be the collagen 241 gene.

And that gene, I explained it just before, is involved in the buildup of the extracellular matrix. And 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 [indiscernible] or the areas of active involvement in the brain.

But the [indiscernible] matrix is where all these neurons and astrocytes are residing or sitting on. It's like a payment, like a street. And if that street is not smooth, like a highway or like pavement, then these neurons cannot function well. And we were able to find that because the patients with the mutation of this collagen in gene in this exosolarmatrix did not respond so well to [indiscernible], representing that they're not as viable as the respective wild-type carriers.

And the good news, though, is the collagen wild tap represents 71% of the overall population. And that was also found in our trials. We had to run about 70% with patients with this collagen 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 Ib/II study.

Okay. And it's my understanding that La Kambi and Cossunla were both approved after a CHMP reexam and that subpopulation data enrich their filing by conferring a more desirable like safety efficacy access. Is that true? And is this any way relevant to Anavex's current position with some of this data, the ABCLEAR2 and ABCLEAR3 data?

It's correct, both licanumab and donanemab, and these are run by large pharma companies. They had been although prior approved in the U.S. reached the same point as we did just as we communicated a few weeks ago, and they underwent the same reexamination and we're able to get approval. I don't want to, I would say, make 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 reexamination process.

But what it goes down to in the assessment of lecanumab in donanemab was the assessment and the judgment of benefit needs to outweigh the risk. And our drug has safe safety no area, and 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 3 to 4 months for the CHMP to give [indiscernible] their next opinions, respectively. So maybe we could see something around April. Is that about what you're projecting?

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 being a small company 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 Europe and even the U.S. Alzheimer's Association kind of put together persuasive arguments for the CHMP to consider during the [indiscernible] and [indiscernible] reevaluations does Anavex have any support like this? Are you aware of any organizations, key opinion leaders or even patients from the trial attempting to persuade this 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 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're doing this in an open discussion. And we are also getting 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 nearing time. So to conclude for me at least, it's pretty obvious to anyone paying attention that blarcamesine should likely be approved for early the Alzheimer's patients and 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 think part of the problem the first time around may have been that it was sort of piece meal analysis and you're introducing analysis as you were going -- but now that you have all analysis at your disposal and the clear narrative, it's my hope that the company will use the reexamination to tell blarcamesine story and earn the approval it deserves. So I hope you have a good rest of the day.

We appreciate the kind words and our expert advisers advises us also to proceed. And so do the patients and investigators, they also advises to proceed and remain committed to do our best. Thank you.

Yes. Thank you, Jessie, and [indiscernible], I don't see any further questions at this time.

Thank you. So we are thankful for your continued interest and trust in Anavex, and 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 [indiscernible] has the potential to address high unmet medical need in early Alzheimer's patients with its clinically meaningful efficacy profile of slowing [indiscernible] decline by more than 30% and sometimes even higher for certain populations and its acceptable safety profile as demonstrated in the Phase IIb 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.