Alterity Therapeutics Limited (ATH) Earnings Call Transcript & Summary

Welcome, everyone. We'll be starting it shortly, just providing some time for everyone to enter the call. Before I hand over the meeting to Alterity's Chair, Mr. Geoffrey Kempler, I'd like to first acknowledge the traditional owners of the various lands on which we are meeting. I pay my respects to elders past, present and emerging. Over to you, Mr. Kempler.

Good morning, and good evening, ladies and gentlemen, and welcome to the Annual General Meeting of Alterity Therapeutics. My name is Geoffrey Kempler, and I'm the Chairman of the company. Today's meeting is being held online via the Computershare platform. This allows our shareholders, proxies and guests to attend the meeting virtually. All attendees can watch a live webcast of the meeting. In addition, shareholders and proxies can ask questions and submit votes. Questions can be submitted at any time. [Operator Instructions] Voting today will be conducted by way of a poll on all items of business. To provide you with enough time to vote, the voting is now live and available for all resolutions. Instructions for voting are contained in the notice of meeting and available by Computershare. If you are eligible to vote at this meeting and have not already submitted your proxy or wish to change your proxy, you can now do so. I now declare voting open on all items of business. Please submit your votes at any time. I'll give you a warning before I move to close voting. I'm advised that the notice of meeting has been properly dispatched and that a quorum of members is present. Accordingly, I declare the meeting formally open, and thank you all for your attendance today. Before proceeding to the formal part of the meeting, I would like to welcome Alterity CEO, Dr. David Stamler, who is currently illustrative, meeting shareholders and engaging with the investment community. I would also like to introduce my fellow Board members who are participating today: Mr. Brian Meltzer, Non-Executive Director and Chair of the Audit Committee; Mr. Peter Marks, Non-Executive Director and Chair of the Remuneration Committee; and online, Mr. Lawrence Gozlan, Non-Executive Director. Also present are Mr. John Roberts, Audit partner at PricewaterhouseCoopers and the team from the company's share registry, Computershare, who will assist in the polling of votes. The order of events for today's meeting will be as follows. I'll first say a few words about the past year for Alterity. We will then proceed with the formal business and the resolutions of the meeting and consider questions on the resolutions. We will then hear from our Chief Executive Officer, Dr. David Stamler. After this, there will be an opportunity for any general shareholder questions to be answered before I will close the meeting. I'll now move to address. Good morning again, and thank you for joining us today at our 2022 Annual General Meeting, and I'm pleased to share with you my Chairman's address for this year's AGM for Alterity Therapeutics. We're hosting the meeting both in person in Melbourne and virtually for people around Australia as well as overseas to ensure that all of our shareholders and corporate partners are able to join us wherever they are. As you'll already be aware, this year, we announced the commencement of the global Phase II clinical trial for our lead candidate, ATH434 for the treatment of multiple system atrophy, MSA. MSA is a rare Parkinsonian disorder that is more rapidly progressing and can be devastating for individuals suffering from the disease. A hallmark of MSA is the accumulation of the protein alpha-synuclein, which can cause neuron loss in the brain. ATH434 is an oral agent designed to reduce alpha-synuclein and preserve nerve cells by restoring normal iron balance in the brain, which is why we believe it has excellent potential to treat Parkinson's disease and MSA. The Phase II is a randomized, double-blind, placebo-controlled clinical trial to explore the effect of ATH434 treatment on imaging and protein biomarkers such as aggravating alpha-synuclein and excess iron. We opened our first site in New Zealand in 2022 in June with the first patient dosed shortly after, a major treatment for us. During the past year, our team has also worked tirelessly towards the expansion of the trial, which has since opened for enrollment in Australia and the U.K. We've also received regulatory approval in Italy and the United States FDA to initiate the trial in those countries. In addition, we continue to engage with regulators and other nations to secure approval to run our trial in these countries. The results of our Phase II trial will cement and inform the design of a definitive Phase III clinical trial. This is an incredible effort as we work towards the validation of ATH434, and I look forward to sharing our progress with you. An important part of our ATH434 program is our bioMUSE natural history study, which has generated invaluable observational data that helps understand how MSA affects our target patient population. The results collected from bioMUSE support the design of our Phase II clinical trial related to patient population and end points, maximizing our chance of success. In collaboration with our research partners at Vanderbilt University, we presented numerous findings at several leading medical conferences this year. To date, our data has revealed valuable insights related to brain iron, improved precision MRI biomarker readings and quantification of motor performance. Over this last year, we've also strengthened our intellectual property portfolio with new U.S. patents that will be instrumental in supporting Alterity's drug development portfolio. This includes 2 composition of matter patents on 230 novel compounds that act as a new class of iron chaperones designed to redistribute the excess iron implicated in many neurodegenerative diseases, including Parkinson's and Alzheimer's disease. As you know, this has been a challenging year in global capital markets with biotechnology stocks being hit especially hard. However, we remain focused on building long-term shareholder value by creating an alternative future for individuals living with devastating neurodegenerative diseases. On behalf of the Board, I would particularly like to thank our CEO, Dr. David Stamler, his executive team and all of our scientific and operational staff for their work over the past year. I also want to thank our directors as well as our shareholders for their support of our business with the continued advancement of our development programs, and we're gearing up for another exciting and productive year for Alterity. We look forward to keeping you updated on our progress. Thank you. I'll now move to the formal business of today's meeting. Our company secretary has confirmed that notice of meeting has been sent to all shareholders and other persons entitled to receive it within the notice period. The matters requiring consideration today are outlined in detail in the notice of meeting. The notice will be taken as read. Alterity Therapeutics' financial statements for the 2022 financial year, together with the auditor's report are in our annual report, which is available on our website. All resolutions 1 through 4 and 7 are ordinary resolutions. This means that to pass that will require more than 50% of votes cast by shareholders entitled to vote and voting for the resolution. Resolutions 5 and 6 are special resolutions. That means to pass that required more than 75% of votes cast by shareholders entitled to vote and voting on resolution. I will now explain the procedure for the remainder of the meeting. Alterity Therapeutics Limited share registry provider Computershare will conduct the voting by way of poll. As mentioned, this poll is being conducted via Computershare's platform, and you can place your vote by clicking on the vote tab on the box on the top right of your screen. Votes will be counted after the end of the meeting and results published on the ASX and Alterity's website. Shareholders can cast their vote using the details received after validating online registration. To validate registration, you'll be asked to enter your security reference number or holder identification number plus postcode if you're in Australia or country if you're outside Australia. If you are intending to vote, you'll be able to finalize and submit vote up until the end of the meeting. I'll remind you at the time of all this. The proxy votes that have been submitted will be set out on the slide shown for each resolution. With some context, the current number of Alterity shares on issue is approximately 2.4 billion shares. Shareholders have appointed the Chair of today's meeting, myself, as proxy voting either for, against or with discretion for all resolutions. As indicated in the proxy form and in the Notice of Meeting, my intention as Chair is to vote all discretionary or undirected proxies held by me in favor of each resolution. I will now move to the ordinary business. First item to receive and consider the annual financial report of the company for the financial year ended 30th of June 2022, together with the declaration of the directors and directors' report in remuneration report and the auditor's report. The company's auditors from PwC is available to answer any questions in relation to the conduct of the audit, the audit report, company's accounting policies or the auditor's independence. Are there any questions in relation to the financial year 2022 accounts?

Yes, there is one question on the line. So I will acknowledge there's a question on the line. It's not in relation to the conduct of the audit or the audit opinion or the [indiscernible]. So I thought you can address that question after the meeting, just addressing the market cap of the company at around $25 million as opposed to the debt assets of $30 million.

So that's still really related to the report. It's just somebody asking them what the share price is.

Basically, that's right.

Okay. Thank you very much, and I appreciate the question. Okay. Are there any other questions related to the actual report that I can address myself or the auditors?

There are no questions in relation to the auditors.

Thank you. As there are no further questions, I hereby take the accounts that we shall move on to resolutions. The following resolution requires 50% or more votes in favor of the resolution. The first is the nonbinding resolution to adopt the remuneration report. I'll take the resolution as read. The proxy results are available on the screen and will be determined by poll at the conclusion of the meeting. Resolution 2 is the reelection of Director, Mr. Brian Meltzer. I will take the resolution as read. The proxy results are available on the screen and will be determined by poll at the conclusion of the meeting. I will take that third resolution is approval to refresh and amend the 2004 ASX plan. I will take the resolution as read. The proxy results are available on the screen and will be determined by poll at the conclusion of the meeting. Resolution 4, approval to refresh and amend 2018 ADS plan. The proxy results are available on the screen will be determined by poll at the conclusion of the meeting. Are there any questions on resolutions 1 to 4, which we will consider in order?

There are no questions from resolution 1 to 4.

Thank you. Please be no questions the following, I will now move on to the special resolutions. The following special resolutions require 75% or more votes in favor of each resolution to pass. For expediency, we'll consider Resolutions 5 and 6 together -- 5 to 6 together. To consider and towards fixed to pass following resolutions as special resolutions. Special Resolution 5 is the approval of 10% placement issue. I will take the resolution as read. Proxy results are available on the screen and will be determined by poll at the conclusion of the meeting. Special Resolution 6 is the amendment of the company constitution. I will take the resolution as read. The proxy results are available on the screen and will be determined by poll at the conclusion of the meeting. Are there any questions on Special Resolutions 5 and 6, which we will consider in order?

Yes, we have two questions. First question is, given the interesting discussion across a range of topics today, including the constitutional amendment, could the Chair undertake to make an archived copy of the webcast plus a fuller transcript? And that will be done, and I'll say that on behalf of him. That will be shared possibly today, maybe on Monday. And there's another question that just came through. Why are we seeking extra placement approval? Are we planning to do another placement? And what is our history when it comes to doing selective placement as opposed to pro rata capital raisings?

So the 10% placement issue was made available for small companies by the ASX some years ago, and I can't remember when it actually came in.

It's probably about 2008.

2008? So you'll find this is a resolution that is included in almost every small biotechnology company as a standby. Our primary obligation as directly is to ensure that we have sufficient funds to conduct our programs for the long-term benefit of shareholders. And given the nature of our industry, that's why the ASX sort of fit to make this provision available and why it's become pretty much commonly accepted. So it's not always used. Sometimes it is, sometimes it's not. But as I said, our primary obligation is to do this to protect long-term shareholder value. Are there any other questions?

Yes. When disclosing the outcomes of the voting on all resolutions today, could you please advise the ASX how many shareholders voted for and against each item similar to what happens with the scheme of arrangement? This will provide a better guide for retail shareholder sentiment on all resolutions and was a disclosure initiative adopted by the lacks of [indiscernible] indexes last year?

So that's some parts of the question actually, I don't know about those circumstances, so I can't make that comparison. But the general question and that will releasing -- we'll be releasing all the information that's required by the ASX. That includes parts of what you have mentioned and things beyond. So they're all -- that reporting is actually -- falls under regulatory arrangements. So unless the questions are very specifically to things that are not part of those regulations, I'm not quite sure what to answer. But I'd be very happy to take a follow-up question, either on record of -- sorry, immediately or later, there's part of the ASX resolutions that don't capture it [indiscernible]. Yes?

So what's been requested is the number of shareholders and the average number of votes -- the number of votes for the meeting as disclosed on the presentation here and after the close of the poll will be displayed those that voted for or against that were open for the Chairman's [indiscernible] and those that abstained.

But I think that will be the questions pertaining to the number of votes. Yes. So I'll take it on Board. So thank you very much. I appreciate the question. Okay. I'll now move on to the last ordinary resolution. Ratification of [indiscernible] issued prior shares. I'll take the resolution as read. Are there any questions on Resolution 7, which we'll consider in order?

There are no questions on that Resolution.

Thank you. So if you're intending to vote on the formal business of the meeting, you should now finalize and submit your votes as voting on all items of business will close in 2 minutes. I will now pause for you to finalize your votes. [Voting]

I declare the poll is now closed. And as mentioned earlier, the results of the voting will be released later today on the ASX once the votes have been counted. It is my very, very pleasure and I can now hand over to Dr. David Stamler to make a brief presentation to provide updates on the company's research and development activities.

Well, thank you, Geoffrey, and welcome to all our shareholders. Good morning in Australia, and good afternoon and evening in other parts of the world. I'm really happy to share the great progress we've made over the last 12 months in advancing the program. As per usual, these are forward-looking statements. So please consult regulatory documents if you want to better understand the risks associated with our activities. Our name Alterity is an English word that meets the state of being different. And I think it truly embodies what we're trying to do with our therapeutic approach, which is we're really trying to change the state of patients and individuals with these diseases from disease to health. And in doing so, we really are trying to improve the quality of life of these individuals. To do so, we are developing disease-modifying therapies that not only address the symptoms of these individuals, but also we're trying to address the underlying pathology, which is a very important goal for many, many neurologic diseases. Our first indication we are pursuing is a disease called multiple system atrophy. For those of you who haven't heard my presentation before, I'll tell you more about that, but it is a devastating condition that has no approved therapy. We have orphan drug designation in the United States and in the European Union. And as Mr. Kempler pointed out briefly, we have our Phase II trial that is ongoing, and we are making great strides in advancing that trial each day. We have a very strong patent portfolio and a very excellent drug discovery group based here in Australia, and we've had excellent composition, amount of patents issued in the last couple of years. This is the development team that is working with me. The 2 folks on the right Margaret Bradbury and Cynthia Wong have worked with me previously to lead 2 drug approvals through the FDA as part of a U.S.-based company called Auspex Pharmaceuticals that was acquired by Teva in 2015. In addition, Kathryn Andrews has provided excellent support providing oversight for our finances and operations. So I'll be talking about Parkinsonian disorders. And Parkinsonism, to step back a little bit, is a syndrome of motor symptoms that many of you have seen in whether it's friends or family members or sometimes even individuals on the street. And this is the slowness of movement, the shuffling gate sometimes you'll see or the tremor. And this is obviously a major source of disability in this Parkinsonism, which is the motor syndrome, is so named because Parkinson's disease is the most common cause of this manifestation. However, there are other forms, so-called Parkinsonian disorders that have that motor impairment, but they also have other symptoms that cause as much or more disability, and they're called atypical for that reason. And also they don't tend to respond as well to the existing treatments. And that's really why we're targeting this disease. And MSA, as I mentioned, it's a bit of a mouthful, but it stands for multiple system atrophy. And I'll tell you more about the disease in a moment. As mentioned before, we are trying to address therapies and develop therapies that will address the underlying pathology, which do not yet exist. This is a summary of the activities we're undertaking in the company. The first line tells you about our Phase II program. The second line is the natural history study, which Mr. Kempler referred to a little while ago. I'm very proud of this study. I think it's been an excellent collaboration with Vanderbilt University, and I think a perfect blend of what we're trying to do for helping patients, along with harnessing the intellectual power and abilities of an academic partner. We also are interested in 434 in Parkinson's disease. We've received funding from the Michael J. Fox foundation, which is a major group in the United States. For those of you who may not know, they have a partner here in Australia called Shake It Up, and we've received funding to evaluate 434 in animal models of Parkinson's disease to try and optimize dosing for future clinical trials. So let's talk a little bit about this protein called alpha-synuclein and how it contributes to disease. So for the non-scientists, that's a nice cartoon of a protein called alpha-synuclein. It's in every neuron and neurons require this protein to communicate with one another. However, in disease, like Parkinson's disease or like MSA, our target, this protein misfolds. It forms clumps inside nerve cells and it can't function. And that's really what you see on the right side of the slide here that it kind of goes from health on the left to disease on the right. And what we're really trying to do is to block that process, to stop those so-called algomers or clumps from forming, so the protein can act normally and you can have normal neurotransmission and a normal function. This is a bit of a complicated slide, but if you look at the figure on the right side, I think it nicely shows that iron, which is in the lower right-hand corner, is kind of driving this vicious cycle where it actually promotes the oxidative stress. It is the root cause of oxidative stress. And as I'll show you in a moment, it also -- this excess iron that's there in disease actually causes this important protein alpha-synuclein to form these clumps. So we're really trying to block that process. This is an important study that came out of the U.K. about 30 years ago. It's an autopsy study, and we see the patients in blue are compared to healthy controls in green. On the left is Parkinson's disease and on the right is our disease target MSA. And you can see that in multiple brain regions where these patients have pathology, they have excess iron, and that excess iron compared to the controls is really what we're targeting. That iron is causing this protein in this fold, it's damaging nerve cells. And our goal is to try and reduce that. So that's an autopsy study, but we're interested in live patients. And you see that nice MRI on the lower left-hand corner comes from our collaborators at Vanderbilt where at the tip of the orange arrow, you actually see the dark red staining material is iron and that corresponds to the pathology study or the autopsy study that I showed you. So this slide kind of summarizes our overall approach. We're trying to bind and redistribute this excess iron, take it out of harm's way. In doing so, we want to preserve this important protein inside cells and reduce the inflammatory responses oxidative stress. And in doing so, the ultimate goal is to rescue neurons. By rescuing neurons, patients function should stabilize or potentially improve. So now let's talk a little bit about the drug candidate, ATH434, I'll just call it 434. For the non-chemist, you see it on the right there, and what's important is it's a small molecule from a drug standpoint, which means it can easily cross the blood-brain barrier, which is really important. It's very important that we can deliver the drug to the site of action. And we'd like to characterize the drug as an iron chaperone, meaning it binds the drug -- sorry, it binds the iron and it moves it out of the cell, so that the cell can function normally. And just to mention before we go on and talk about the clinical development, we've had extensive discussions with regulators around the globe and have incorporated their feedback into our development program. So this is a data slide, which might be a little heavy for the nonscientists. But suffice it to say that in that table on the bottom part of the slide, you see that the 434 iron binding kind of in the middle is stronger than the binding of iron to alpha-synuclein. So it's going to actually reduce that pathologic misfolding that I mentioned, but it's not going to interfere with that protein on bond called transferrin that's so critical for moving iron around the body. And we think being in this had a zone of the sweet spot is really ideal for the drug to do its work, but to not interfere with our normal bodily functions. On the right side of the slide, you kind of see what this means in animals, and we've shown that we can reduce the alpha-synuclein aggregation, as I talked about. We can block that iron increase. And in doing so, we can block the oxidative stress. These are the animal models that you really like to see as a drug developer and what's necessary to really justify going into clinical trials. These are Parkinson's disease animal models, 2 different kinds. One is a genetic model on top. The bottom is a toxin model, and you see nicely that we can reduce the aggregation of that alpha-synuclein and we can also preserve neurons. Now these are animal models of multiple system atrophy. Again, quite a bit of data on these slides. But I think what's important is there are 2 independent experiments, 1 done here at the Flory Institute in Australia, the other one done at a leading center in Austria. And we see complementary data. I can't present all the data to you, but we see reductions in alpha-synuclein, preservation of neurons and reduction in pathology, and then in the bottom right-hand corner of the slide, improved motor function. And that's really the ultimate goal is to try and improve function in these patients. Tell you a little bit about multiple system atrophy. I've mentioned these patients have a Parkinsonism, but they also have uncoordinated movements that causes them to have increased falls. But they -- in addition, they also have difficulty maintaining their blood pressure. They can't maintain or bladder control or bowel function. So it's really a terrible disease that affects several important systems. So our goal is to target early-stage patients. And you can kind of see the brain image on the left is an early-stage patient. We really want to target individuals at that stage of disease because they have the most neurons to preserve, and they have the greatest function to preserve. This is a cartoon that I think tells you what's so terrible about MSA. So you see at the bottom of the scale is a time course. And basically, the typical patient will live about 7.5 years after symptom onset and more than 50% require a wheelchair after 5 years. So our goal is to target patients in that second phase there where it's as clinically probable, right when they present with motor features, not too advanced. And in doing so, if we can interfere with that disease process, we can prevent them from requiring a walker, a wheelchair and hopefully extend their survive. Before we completed our -- started our Phase II trial, we conducted this Phase I trial here in Australia, which was a well-controlled study in healthy volunteers. And we looked at single doses up to 600 milligrams, multiple doses up to 250 milligrams. And we also looked at that both in younger adults as well as a cohort of patients or volunteers, excuse me, that were over 65. The left side of the slide shows you the blood level data, which is -- what you'd really like to see as a drug developer, as you increase the dose, you get increased exposure. And we saw a half-life of drug, which means how long the drug stays in the body of about 9 hours, which allows us to dose the drug twice a day. On the right side of the slide, you see this is spinal fluid concentrations plotted against the blood levels. And you see, number one, there's a very nice correlation, meaning that the drug does easily cross into the blood brain area, which is important for acting at the site of -- and we also know that with our clinical doses in the Phase II trial that we can exceed the concentrations that are associated with efficacy in those animal models that I just showed you. So all very important for minimizing our risk and delivering a good therapeutic option. This is the safety of the drug. Again, lots of zeroes, meaning no patients had adverse events leading to withdraw. No patients had serious adverse events, and we really saw a similar safety profile between active drug and placebo and also similar adverse event profile between younger adults and older adults, and no cardiovascular signal, which can be cause of problem for drug candidates. So now I want to mention the natural history study that Mr. Kempler alluded to. We call this bioMUSE for biomarkers for progression. And this is a tremendously important study because we are aiming to study early-stage patients with MSA, and this has not been done before. And the first objective there is really the critical one. We wanted to inform and derisk our Phase II study. This is a complex disease, and we really felt it was important to learn as much as we could before embarking on the treatment study. So we recruited a population that mirrors the patients we're enrolling into the Phase II study. We followed them for 12 months, which is the treatment period we will be using in the Phase II study. And then we looked at a whole host of biomarkers, both MRI biomarkers, biomarkers in spinal fluid and in blood and in skin. And we looked at wearable movement sensors, which is an emerging technology that's quite important for looking at motor behavior that you can't assess in the clinic. And then we give all the clinical endpoints that we want to put in a Phase II study, as you can imagine. And this slide is, I think, a really nice summary of the beautiful work that our collaborators at Vanderbilt have done over the last several years. So starting on the left, they have optimized these advanced MRI methods, and we've been able to identify a so-called iron signature in our target patient population so we can use that to identify patients coming into the trial. Next, they did use the data from the study to develop a new MRI template, which is really critical for -- it's basically a map. And the more accurate your map, the greater precision that we can have in quantifying things like iron or other biomarkers in the brain. The next panel, iron distribution, I think, is a nice visual depiction of how we can actually quantify the iron in the brains of these patients. So you see in red is the healthy controls. And then the blue distribution in that graph is an MSA patient. So you can easily see with iron on the X axis that we have a rightward shift, which would mean an increase in iron in the MSA patients. So we're using this along with our statisticians to develop novel quantitative measures for looking at the iron in the brains of these patients. Next, we looked at alpha-synuclein profiles in the spinal fluid of these patients. we can clearly distinguish an MSA patient from a Parkinson's patient. And then finally, the wearable sensors on the right side looks at this quantitative assessment of motor function over time, as I mentioned, in ways that you can't capture with a neurologic exam in the clinic. So this is really a novel approach. And I think I can confidently say that we are the first trial in this disease area to incorporate some of these biomarkers into our patient selection in order to derisk the Phase II trial. So turning to the Phase II study itself. This is obviously a randomized, well-controlled study aimed at looking at efficacy and safety in our target patients early MSA. We're aiming to recruit 60 patients in Australia, New Zealand, Europe and the United States. As mentioned, 12 months of treatment, we're looking at 2 dose levels of ATH434 or placebo. And the primary endpoint is the change in iron as measured by random RI. And we think this is really critical that we can demonstrate target engagement where we know the pathology is occurring, but were obviously very important in assessing the clinical benefit in patients. So we're looking at all the clinical scales that would be necessary to support the approval of the drug. And then we're going to use the data, as Mr. Kempler mentioned, from this study to adequately power on the definitive trial that is going to support the approval. But this is going to be the most important learnings that we'll do in the development program. That's the design on the left I just told you about and then to just talk a little bit about the primary endpoint on the right side of the slide. These are data from our natural history study, where we actually plotted on the x-axis that's called the unified MSA rating scale. That's the most widely accepted scale to assess disease severity. So as the numbers get bigger, the disease severity is worse. And then on the y-axis, is the iron content. So we can see that there's a nice correlation between the 2. What we're aiming to do is to try and move patients kind of back towards lower iron amounts and less disease severity quite simply. And that's really why bringing iron is such an important end point for us. We have done a careful commercial analysis based on interviews with 30 U.S. neurologists, specialists and generalists. And I think with rather modest commercial assumptions, both market size and pricing of an orphan drug, we see that there's a substantial value of over $700 million just in the United States alone, just in MSA. The clinicians clearly recognize a substantial unmet need in this patient population. They had a very strong intent to prescribe because the drug itself addresses the underlying pathology, not just the symptoms, and they nicely recognize the -- they really recognize the value of an oral drug. Many treatments in this space both for Parkinson's and MSA are antibodies, which have to be given intravenously, chronically, and that's not something that patients or clinicians like very much. So in summary, we are targeting MSA, an orphan disease that has no approved therapies. We've made great progress on our natural history study, which is really fed into optimizing our Phase II design. I've talked about the progress we've made with the Phase II trial with ATH434. Our development team is working incredibly hard, and I'm really proud of the work they've done to date, and I know we're going to have exciting results in due time. Our drug discovery group has generated recent composition matter patents that support next-generation drugs moving into Parkinson's disease is our goal. And then our cash balance is strong with other numbers indicated on the screen. We've met those milestones so far in 2022, and I will hope to continue delivering excellent results in 2023. So thank you for your attention. I'm going to now turn the microphone back to Mr. Kempler.

Thank you, David, for an excellent presentation. Does anyone have any questions for Dr. Stamler?

There are no questions for Dr. Stamler, but we have a couple of general questions.

Yes, please.

First one is, we have $180 million of accumulated losses. Where did all the money go when net assets are only $35 million, and the market cap is $25 million?

First of all, thank you very much for the question. The program is that the money raised over many, many years has been spent on Alzheimer's disease for the first part of the company's history. We did quite well in terms of our advancement of the clinical trials and [indiscernible] a strategy to deal with it, and there's still a lot of scientific value in that. But it became apparent, and we've made all these announcements a number of years ago, that in order to use the drug that we were using at the time at the dose that the FDA wanted us to use and justify proceeding with the amount of money that would have been required. And if the questioner is well aware of the global effort to treat alpha-synuclein by targeting beta amyloids may be well aware, so thank you for the question once again, that probably over $100 billion of spend tracing this potent protein around the brain by actually dozens of different companies over dozens of years. And it's really only this year that one company got an approval. I think that was actually last year with mixed results on the market, but some positive quarter coming through on it now. So the valuation of the company reflects what we're doing today. And I would love to see a much higher market capitalization. But I think that will probably go through 90% of the biotech companies on the market, 99% I'm hearing from another shareholder. And yes, it is very, very frustrating, and we have nothing but simply for the question because we experience it every day. We also look forward to when the markets can properly value shares, which they can only reflect through their buying power, right? And so that's why -- and you see a lot of volatility in different shares. You see even more in some of the tech bundled stocks, and that's the reality of the stock market. So that's why money is raised over the years. But I think that the money has been -- personally, it's been a [indiscernible] disappointment to me that Alzheimer's didn't succeed globally from all of those companies. But I think what Dr. Stamler has to work with now is a phenomena -- is benefiting from that huge investment over many, many years of understanding misfolding proteins, understanding how [indiscernible], which are endogenous to our brains can help with diseases. So I think that the whole ATH-MSA journey has been truncated by decades because Dr. Stamler can have to start de novo with all those things that the high level of investment we need to in the years before he came to us.

Yes. I'd also like to add. I mean, I understand that the share price is disappointing, and it's something we're focused on and we strongly believe we can create value by what we're doing with the development program. To echo something that Geoffrey just said, a lot has been learned about drug development in neuroscience in the last 10 to 15 years. There's been a focus on earlier-stage disease, and there's been a real focus on biomarkers. When the Alzheimer's program was undertaken not only for us, but for several other companies, people are looking on later-stage diseases. So I think we've learned a lot in terms of how to run clinical development programs and how to identify the right patients. So it is a journey. But I'm also confident that as we continue to advance the program, we have good opportunity to build.

Thank you very much for that. Are there any other questions?

Yes, one for David. Given the current cash balance, what is the current rate of cash burn and the likely need for further funds to complete your Phase II program? And what is the capital strategy going forward?

Yes. Thank you for the question. So the cash balance is supportive of our plans to run the Phase II study. Our capital strategy at this moment is obviously one of watchful waiting. We know that at some point during the conduct of the Phase II trial that we'd like to raise additional funds to support our ongoing research activities, where we've made good progress to adequately prepare for Phase III based on a positive Phase II result. So we're very watchful of the market. We've got several investors that are interested in our work, and we've got ongoing conversations with pharma companies that are also potentially interested in our activities. So we're taking a very holistic approach and pushing forward with the development program, while we're waiting for markets to stabilize where we can actually make a productive decision down the road.

Thank you. Next question, just a general question. With 2.4 billion shares on issue and stock trading at $0.01, why don't we do a 1 for 100 share consolidation?

I won't address the specific mechanics of that, but we definitely need to respond to the current share price on NASDAQ and that will require that we make some changes to how our capital table looks. So I won't disclose how we will attain to do that, but we've been very open in our announcements about the rules that we need to comply with under those [indiscernible]. Any other questions?

Yes. Final question, which of our directors is next -- most likely to retire and who is up for election next year? Do we have enough headroom on our fee cap authority if we wanted to expand the Board? And what is the constitutional cap on the Board numbers?

Right. So I'm not -- definitely not going to be accurately respond to any questions about directors, but I can answer a question about the constitution. What was the question about our constitution again, if you could repeat that?

Yes. Do we have enough headroom in our fee capital authority if we wanted to expand the Board? And what is the constitutional cap on Board numbers?

Well, the answer to your first question is yes, and we're just checking the constitution because I don't have the detail of the constitution you might..

[indiscernible]. And in the next elections..

So in the next election, we work out what that is. Okay. I'm happy to take a follow-up question, if that's clear. Are there any other questions there?

We have no more questions at this time.

Okay. Thank you very much. So I'd like to thank everyone again. I'd like to thank my fellow directors, our shareholders. I'd particularly like to thank everyone online who made the effort to ask questions. I would very much appreciate that. And thank you, everyone, for your ongoing support of Alterity Therapeutics. This concludes the formal business of the meeting. I now declare the meeting closed. Thank you.