Alterity Therapeutics Limited (ATH) Earnings Call Transcript & Summary

Good day, everyone, and welcome back to this Hidden Gems Webinar. Thank you all for your Friday time. We always appreciate it. Today, we're discussing oil and gas, lasers and LED, neurodegenerative diseases and client engagement. And don't forget to ask questions. You can ask questions by typing in the box provided. And if we have time to answer those, we will ask them. If not, we'll come back and revert back to those questions and have the CEOs either ask them, answer them directly or will shoot them, throw to them over the weekend. So make sure you got your name and your e-mail on those questions. First up, we have Alterity Therapeutics, ASX code ATH. It's got a market cap of around $17 million. We have with us Dr. David Stamler, who's the CEO. The company is a clinical stage by a technology company dedicated to creating an alternative future for people living with neurodegenerative diseases. David is coming to us live from California. There's a storm on the way. David, thanks for your time.

Thank you, Tim, and thank you to the audience. I'm very happy that you join me today and taking time out of your day, so you can hear about the excellent progress that we've been making in the recent past as we've been developing novel treatments for neurodegenerative disorders. Next slide. These are our forward-looking statements. Next slide. At Alterity, we are developing disease-modifying therapies that really address the underlying pathology and the aim is to try and slow the disease progression. Our novel drug candidate, which we refer to as ATH434 targets proteins that are implicated in the neurodegenerative process, and this includes diseases as Parkinson's and MSA. Our first indication, multiple system atrophy, or MSA, is a devastating degenerative condition with no approved treatments, and it has achieved orphan drug designation in the United States as well as in the European Union. I'll be telling you in a moment about an ongoing Phase II clinical trial to demonstrate target engagement and efficacy of this drug in the target population. We also have a very active discovery program and a strong patent portfolio to show for that. And I'm also happy to say that the team that is working with me, we've had success in bringing 3 neurologic drugs to the market in the U.S. Next slide. So I'll be focused on Parkinsonian disorders, which really include Parkinsonism. And Parkinsonism is a motor syndrome that you've probably seen in friends or family members that includes individuals with slow movement, stooped posture, tremor or stiffness. And it's so named because Parkinson's disease is the most common cause of this motor syndrome. Now moving forward, we know that there are other disorders that include Parkinsonism and are called Parkinsonian disorders and one includes our target indication, multiple system atrophy, another one is called PSP. And these disorders are less common, but they also have not only the motor impairment of Parkinson's disease, but they also have associated symptoms that cause as much or more disability than the motor impairment. Importantly, current therapies for the -- all these diseases are really addressed at targeting the symptoms and not the underlying pathology of the disease, and that's really what we're aiming to do. Next slide. So this slide basically summarizes our development portfolio. First, I talked about our lead product, ATH434 that we are advancing in Phase II for multiple system atrophy. That study is ongoing, and I'll tell you more about that in a moment. I think a really exciting part of our development program is the next item, which is our natural history study that we call bioMUSE. This is based on an academic collaboration we've had with Vanderbilt University for several years. And I think this is a really interesting aspect of the development program, which has really derisked our Phase II study. 434 in Parkinson's disease, that's something that we are evaluating with a grant from the Michael J. Fox Foundation in the United States, and that's to help us pick doses for clinical trials in Parkinson's disease. And lastly, I've already mentioned our drug discovery program. Next slide. So our approach towards treating these diseases is illustrated nicely from this study, which comes from about 30 years ago, and it's an autopsy study done in patients with Parkinson's disease on the left and MSA patients are target indication on the right. And we see patients who are in blue, healthy controls of the same age are in green. And we see in both diseases that in areas of pathology, these are brain regions shown, that there's increased iron compared to the controls. And this is really what we are targeting with our therapy. Now moving forward, we see that we can now measure iron in the brains of living patients as opposed to the autopsy study. And this -- the lower corner of the slide -- lower left corner of the slide demonstrates an MSA patient. At the tip of the orange area, you see that dark red staining material. And that's really what we're targeting with our therapy. Next slide. So to summarize the overall approach is we are binding and redistributing excess iron in these areas of pathology. In doing so, we're reducing the clumping of a protein called alpha-synuclein. That's a really important protein in all nerve cells for them to function properly. So by reducing that clumping, we can actually rescue neurons, and in doing so, the overall aim with our therapy is to modify the course and slow the course of disease. Next slide. So a bit about 434 you see depicted on the right side of the slide. It is a small-molecule drug that addresses the underlying pathology of disease. We refer to as an iron chaperone, meaning it binds iron that's increased in areas where it shouldn't be, but it doesn't strip iron from the body. It's an easy-to-use drug. It's an oral tablets. It's given twice a day. And we've shown that it's readily absorbed into the body and delivered to the site of action in the brain. I mentioned that we have orphan drug designation in both the U.S. and European Union. And we've had several development discussions with both the FDA and the European agency, and they've really endorsed the approach that we're taking. Next slide. So I'll be telling you now about multiple system atrophy itself in the disease and in our clinical development program. Next slide. So as I've told you before, MSA is a rare disease. It's highly debilitating and unfortunately, rapidly progressive. Patients survive for an average of 7.5 years after symptom onset. We've talked about the motor impairment already. These patients also have the clinical feature of impaired autonomic function and autonomic function really is part of the nervous system that controls your ability to maintain blood pressure, bladder control, bowel control, et cetera. And as you can see in the picture on the right side of the slide, over the progression of the 7 to 8 years after symptom onset, more than 50% of individuals wind up in a wheelchair. And our goal is to really intervene in the second stage, you see depicted there, where patients have motor symptoms, but do not yet need a walking assistive device like a walker or a wheelchair. Importantly, we and others have shown that brain iron correlates with disease severity in MSA. And our goal is to really reduce that brain iron and reduce disease severity. Next slide. We have conducted a Phase I clinical trial with 434 demonstrating that the drug is well tolerated with no serious adverse events and no adverse events leading to withdrawal. Next slide. This is the natural history study I mentioned previously. This study is designed to inform and derisk the Phase II study. So just to be clear, the natural history study is a clinical study where there is no experimental treatment, but we take patients that have our target disease that we think that we want to study. And the goal is to really identify certain clinical endpoints that we think are important to track the disease and also biomarkers, which are basically things you can't see or feel like an MRI or like a fluid in your body that helps us understand how the disease is progressing. So we studied about 20 patients, followed them for 12 months and looked at various biomarkers that you see on the slide, both MRI, fluid biomarkers in these wearable movement sensors, which are really a part of almost all movement disorder trials these days. And then the clinical endpoints that we need to demonstrate that the drug was effective down the road. Next slide. So just to reiterate, the goal of this natural history study was to characterize these patients with the aim of optimizing patient selection, develop -- assessing endpoints with precision in the clinical trial and then finally, piloting clinical measures that we think are going to be important for the patients and what they experience. So moving forward, we see that the advanced MRI methods that I showed you earlier, we've now been able to show in early-stage patients, help us identify these patients with a high degree of confidence. Moving forward to the next part of the slide, we have also in this study developed a new MRI template as well as novel methods for quantifying the iron in different brain regions, and these are really going to enable us to assess the important endpoints in this trial with precision. And then finally, moving forward, we are piloting clinical measures so we see wearable movement sensors and the decline in the number of minutes walked in the subject on the left, and then the urinary symptom profile are demonstrating that we can capture the abnormal symptoms these patients experience with the aim of demonstrating improvement in the clinical trial. Next slide. I believe we'll summarize the Phase II clinical trial design. This looks a lot like the natural history study, except now there's treatment involved. So this is a randomized double-blind placebo-controlled Phase II study looking at safety, efficacy and target engagement or biomarkers, as I said, those fluids or MRI measures that you can't really see or feel that a patient can. We're looking at 60 individuals in Australia, New Zealand, Europe and the U.S. We are -- we have regulatory approval in all those regions and are enrolling in several countries. Our primary endpoint is that change in iron content is measured by brain MRI because we know that contributes to the underlying pathology. And then you see all the secondary endpoints, the clinical measures that we need to get the drug approved ultimately. So it's a 12-month treatment. You see the treatments on the below -- on the bottom of the slide, ATH434 and [ 2 higher dose ] placebo. And we thought we'll treat patients for a total of 12 months. Next slide. From a commercial perspective, we have conducted marketing research with 30 U.S. neurologists, half specialists, half generalists and estimate peak sales based on relatively conservative assumptions of up to USD 725 million. I mean that's in the U.S. alone for MSA alone. Clinicians clearly recognized there was a substantial unmet need for treating these patients because there's nothing available for them. And they had a very strong intent to prescribe because they recognize that our treatment really targets not only symptoms, but the underlying pathology of the disease. And they also very much appreciate the fact that this is an oral drug and not an intravenous drug or a drug that needs to even be given into the spinal fluid. So next slide. So in summary, Alterity, we are poised for progress over the next several months. We are targeting an orphan disease with no approved treatments. We have derisked our Phase II study by conducting the natural history study. And our Phase II trial is making excellent progress enrolling in multiple regions. And importantly, their development team has a proven track record of getting across the [ finish at the ] FDA. Our drug discovery team has been very successful in the recent past by generating novel composition of matter patents that will really support us taking new drug candidate into Parkinson's disease. And with that, I will stop and entertain any questions that you might have. Thank you.

Thanks, David. Your internet is a little bit patchy just towards the end there, just -- that storm must be coming. Quick question. How does the actual treatment benefit the patient?

Yes. So these patients declined significantly, Tim, over the course of their illness. They can't -- they have difficulty walking, their bladder function is quite poor. So our aim is by treating them early in the stage of their illness, that they can actually maintain self-care that they can become -- they can stay ambulatory and they can really preserve their quality of life. So we're really trying to freeze them in time when they're early in their disease so they don't become dependent on others. And so they have a good quality of life.

And in general, you announced the market your Phase II clinical trials for 434 in both Italy and the U.S. And a few days ago, you announced the first participant in Italy has been dosed. What's the sort of expected time line for results from that trial?

Yes. So we haven't disclosed the details of the results, but we do project, if you look at our milestone slide, the last milestone we've indicated is we expect enrollment to close at the end of third quarter calendar year '23. And with 12 months treatment, and then additional -- some additional time to clean the data and lock the database, we anticipate that we should have results in the -- towards the end of 2024.

And any news on when patients in the U.S. will be ready to go?

Yes. So we have sites that are active here. We've also kind of signaled that we expect to be enrolling in the U.S. later this year -- sorry, later this quarter, so sometime later this month is my expectation. And we've got multiple sites coming on in all regions. We also think after the U.S. that we should be enrolling in Australia, sometime by second quarter with -- there's a lot of excitement with the trial. We're getting a lot of energy from the clinical investigators.

We've got an audience member specifically asking a question around California trials. So the email is there, and I'll reach out to him or by yourself. The other question is always where the biotech is funding, what's the funding pipeline look like you're well-capitalized at $25 million, cash that is...

Yes. So we are capitalized to complete the Phase II clinical trial. So that's -- so we feel like we're in a very good position. There's obviously more we'd always like to do. We look at additional indications with 434, additional orphan indications. We'd always like to do new studies and most importantly, prepare for the next phase. So obviously, the market is tough at this time, but we are always in discussions, and we're always interested in expanding our activities when right, but we feel very good that we have the capital to complete the Phase II trial.

Thanks, David. That's all we have time for you, well-funded and doing some very important work. There's quite a few other questions, if you don't mind, if you have time, answer those online. If not, I'll reach out over the weekend. Thank you.

All right. Great. We'll do. Thank you, Tim, and thanks to everyone for participating.

Thanks.