บทถอดความฉบับเต็มของ Interview: The ASX-listed company working to beat a devastating disease

diseases where there is excess amount of this reactive iron that causes problem. So knowing that we had a compound that targets the iron, that limits the universe of diseases that we could go after. Now being a small company, it's much easier for us to target a disease like multiple systematrophe, for which there are maybe fifteen to fifty thousand patients in the United States, versus Parkinson's disease, which is like, you know, a million people. So that's a starter. The other thing is MSA is a disease where elevated levels of iron in the areas of pathology is well established. So for that reason and the fact that there's no approved therapy for the disease makes it an excellent candidate for our drug. 00:04:02 Speaker 1: Okay, and in Layman's terms, how does the drug work, then presumably it addresses this iron issue. 00:04:10 Speaker 2: It does. Yeah, So, as I mentioned, there's excess iron, and we don't know completely how why there is excess iron, but it is an observation that's well established. And what the drug does is it really acts as a chaperone, meaning it binds the iron inside the cell and it helps remove it. It helps it eflux it from the cell. Sometimes it can help increase the storage of the iron in the cell, or it can help sequester it, so it's not causing all these problems. When it's in excess. This reactive iron that I'm talking about, it actually causes important proteins to misfold and form aggregates, and therefore the neurons can't function. That protein that I mentioned is important in all neurons and for their function. The excess iron itself also is the source of free radicals and observative stress. So those free radicals damage DNA and lipids inside cells. So by targeting it and kind of getting that excess iron out of the way, we hope to preserve neuron function and we hope to prevent that oxidative stress thereby saving neurons and preserving function. 00:05:23 Speaker 1: I'm learning a lot this morning. We'll be back straight after the break. I'm speaking to Dr David Stemla, CEO of Alterity Therapeutics. David, we know what it is that four three four is doing. Tak me through the clinical trials you've been doing. 00:05:47 Speaker 2: Yeah, So what we've done three patient trials over the last several years, and briefly I'll talk about the first one, which was a natural history study that involved no treatment, where we studied our target patients to enroll in the trial. And what we learned from that study was which biomarkers in which are kind of endpoints to track the target engagement and see if we're slowing down the disease. And it also helped us refine the criteria for enrolling patients into our two treatment studies. So that was a really important study to help de risk the Phase two program. The next two studies are treatment studies. The main study that's ongoing right now enrolled about seventy five patients and they were treated with two doses of our drug for a twelve months. Now. That study completed patient treatment in November, and we should have results at the end of January or early February. The other trial that we are doing is a similar design trial, except that everyone's receiving active treatment and it's a smaller study in advanced patient and we got the results from that study in July of this year, and that showed us some very encouraging things. Number one, it showed that about thirty percent of the patients actually had stabilization or improvement of symptoms, which is rare in such a rapidly progressive disease. We also showed that objective biomarkers that I referred to ones in the blood and the spinal fluid as well as on MRI, showed that we saw stabilization of these biomarkers compared to other patients who were not treated. And I think the final important takeaway from that study was that those patients who responded had the earliest stage of disease. And that's really important because the main trial we're doing is in earlier stage patients, so that really has increased our confidence and giving us, you know, a lot of optimism going into the data readout for early next year. 00:07:54 Speaker 1: Okay, so way too from here. Assuming the data read out early next year is promised and enough to put you into the next stage of clinical trials, is that how it works? You then go into stage three And what's that involved? 00:08:10 Speaker 2: Yeah, so there's well, there's two pathways with a positive study. Now, if we you know, kind of have a knockout result and it's really strong on biomarkers and clinical endpoints, we would then go talk with the FDA about getting an accelerated approval based on this trial that we're doing right now. And that's something that there is recent experience with and the FDA is clearly demonstrated and interest in doing that for serious diseases like MSA for which there's no approved therapy. Now, if we see efficacy but the FDA does not support an accelerated approval, we would then go onto that next phase that's so called phase three study. It would probably be maybe twice the size of the study that we're doing now, looking at similar treatments, maybe one to two treatment, and we would learn a lot from the ongoing study in terms of how the how long the treatment would be, what endpoints we've been used, and exactly what kind of patients we would want to enroll in that study. 00:09:07 Speaker 1: Okay, so we've been talking about MSI are your learnings, I mean maybe the treatment, but perhaps it's the learnings potentially applicable to a broader range of illness. 00:09:18 Speaker 2: Yeah, that's really the case, and that's a kind of a corporate strategy we've been interested in a long time. MSA is a small orphan disease for which there's a great need. But we know that that Parkinson's disease in particular has similar pathology underlying pathology as MSA. They have this protein that misfolds and aggregates the same protein. The same happens in Parkinson's disease. We also know in the key areas of pathology in Parkinson's disease they get elevated levels of iron. So with efficacy demonstrated in multiple system atrophy, our next move would be to try and turn two Parkinson's disease. That would be the next option. We've recently presented some other data basic science data demonstrating we have potential use of our drug in another orphan disease called Friedrich's attacks, where iron imbalance is a cardinal manifestation of the disease and something that we could target with our drug. And there are others I will belabor the point, but it is clearly a useful target. 00:10:26 Speaker 1: So a ways to go. You have had a long distinguished create in medicine in all like in different forms of it. You have to be pretty patient, though, don't you when you're running a company like this, because ververy high. There must be quite a few I don't know where the necessary loads, but it just takes a long time. 00:10:45 Speaker 2: You're right, it does. I mean I came to Alterity over seven years ago and we picked this molecule, we picked this development program. We've done a lot of non clinical work, a lot of basic science work as well as you know, I'm several studies in healthy volunteers to get ready for this stage. In these studies themselves, we started in twenty twenty two, So you're right, it is. It is a long process, but it's one that you know. It's the nature of the beast. You just have to you do have to be patient, You've got to be diligent, and as I like to say, in addition to my role as a CEO as a drug developer, I am a serial warrior and I think that's one of my personality traits. But I think it causes me and all of my team members to pay very close attention to detail and give our drug every bit of chance to succeed. 00:11:43 Speaker 1: Good luck with it, David, thank you for talking to Fear and Greed. 00:11:46 Speaker 2: Great. Thank you for having me. 00:11:48 Speaker 1: That was doctor David Stamler, chief executive of Alterity Therapeutics, a great supporter of this podcast. This is the Fear and Greed Business Interview. Remember this is general information only. You should always seek professional advice before making any investment decisions. Join us every morning for the full episode of Fear and Greed, daily business news for people who make their own decisions. I'm chanelma Enjoy your day.