1 00:00:05,640 --> 00:00:07,920 Speaker 1: Welcome to the Fear and Greed Business Interview. I'm sure 2 00:00:07,960 --> 00:00:12,360 Speaker 1: an ailmark. Medical technology companies are fascinating businesses because at 3 00:00:12,360 --> 00:00:16,080 Speaker 1: their core, they're trying to solve a problem. And if 4 00:00:16,120 --> 00:00:18,200 Speaker 1: they can do that, and if they can clear the many, 5 00:00:18,239 --> 00:00:21,000 Speaker 1: many regulatory hurdles along the way, then they can not 6 00:00:21,079 --> 00:00:24,480 Speaker 1: only help the people live better and longer, healthier lives, 7 00:00:24,640 --> 00:00:29,240 Speaker 1: they can also deliver strong returns to shareholders. Alterity Therapeutics 8 00:00:29,320 --> 00:00:32,680 Speaker 1: is an ASX listed company that's focused on developing treatments 9 00:00:32,920 --> 00:00:37,760 Speaker 1: for devastating conditions like Parkinson's disease and multiple system atrophy, 10 00:00:38,240 --> 00:00:40,199 Speaker 1: and it's a long way down the path, with one 11 00:00:40,200 --> 00:00:43,479 Speaker 1: of its treatments having just completed its phase to clinical trial. 12 00:00:44,159 --> 00:00:48,720 Speaker 1: Dr David Stemler is the chief executive of Alterity Therapeutics, 13 00:00:48,720 --> 00:00:51,000 Speaker 1: which is a great supporter of this podcast. David, Welcome 14 00:00:51,040 --> 00:00:51,720 Speaker 1: to Fear and Greed. 15 00:00:52,120 --> 00:00:54,240 Speaker 2: Hello Sean, great to be here. Now. 16 00:00:54,240 --> 00:00:58,040 Speaker 1: I just mentioned your treatments known as ATH four three four. 17 00:00:58,400 --> 00:01:01,960 Speaker 1: It's targeting multiple system atrophy. You're going to have to 18 00:01:02,000 --> 00:01:05,560 Speaker 1: explain a few things to me. What exactly ease multiple 19 00:01:05,560 --> 00:01:09,520 Speaker 1: system atrophy MSA. I know it's a rare disease, but 20 00:01:09,560 --> 00:01:12,280 Speaker 1: what is it so MSA. 21 00:01:11,880 --> 00:01:16,640 Speaker 2: Is what we refer to as a Parkinsonian disorder, meaning 22 00:01:17,120 --> 00:01:22,160 Speaker 2: these individuals who are affected have symptoms of Parkinson's disease 23 00:01:22,240 --> 00:01:25,680 Speaker 2: that we've all probably seen in friends or family members, 24 00:01:26,160 --> 00:01:30,119 Speaker 2: but they also have other symptoms that cause as much 25 00:01:30,280 --> 00:01:33,760 Speaker 2: or more problems than the motor symptoms. So in addition 26 00:01:33,800 --> 00:01:38,200 Speaker 2: to the slow movement and shuffling gait that you've sometimes seen, 27 00:01:38,959 --> 00:01:43,600 Speaker 2: they also have uncoordinated movements, which leads to common balance 28 00:01:43,720 --> 00:01:47,360 Speaker 2: problems and falls. But they also have impairment of the 29 00:01:47,440 --> 00:01:50,560 Speaker 2: autonomic nervous system. Also another word for that is like 30 00:01:50,640 --> 00:01:54,320 Speaker 2: the automatic nervous system, and what that means is that 31 00:01:54,360 --> 00:01:59,400 Speaker 2: controls things like your blood pressure or heart rate, bowel function, 32 00:01:59,520 --> 00:02:02,720 Speaker 2: bladder function, things you don't have to think about. Unfortunately, 33 00:02:02,720 --> 00:02:05,520 Speaker 2: with the degeneration of that part of the nervous system, 34 00:02:05,920 --> 00:02:10,079 Speaker 2: patients often have a difficulty maintaining their blood pressure when 35 00:02:10,080 --> 00:02:13,040 Speaker 2: they stand up or even if they eat a large meal. 36 00:02:13,200 --> 00:02:17,519 Speaker 2: So these our debilitating symptoms, and the disease is quite 37 00:02:17,560 --> 00:02:20,560 Speaker 2: aggressive as well. It progresses about three times as fast 38 00:02:20,560 --> 00:02:21,960 Speaker 2: as Parkinson's disease. 39 00:02:23,400 --> 00:02:28,880 Speaker 1: I'm interested in how you end up trialing drugs that 40 00:02:28,960 --> 00:02:33,960 Speaker 1: can help that particular disease. I'm always fascinated by the 41 00:02:34,040 --> 00:02:37,880 Speaker 1: story of how a company like yours gets to doing 42 00:02:38,040 --> 00:02:41,480 Speaker 1: trials on that particular rate disease and that sort of 43 00:02:41,520 --> 00:02:43,000 Speaker 1: subset of Parkinson's. 44 00:02:43,560 --> 00:02:46,000 Speaker 2: So how do we get to MSA, Yeah, it's a 45 00:02:46,000 --> 00:02:50,640 Speaker 2: great question. Well, firstly, the company has a long history 46 00:02:51,000 --> 00:02:56,200 Speaker 2: of discovering molecules that target certain types of metals that 47 00:02:56,240 --> 00:03:00,840 Speaker 2: are involved in EU degeneration. And the compound that we're 48 00:03:00,880 --> 00:03:04,360 Speaker 2: talking about today at h four three four, I'll just 49 00:03:04,400 --> 00:03:07,480 Speaker 2: refer to it as four three four. It was discovered 50 00:03:07,480 --> 00:03:10,480 Speaker 2: in house, and it targets iron, and it targets a 51 00:03:10,480 --> 00:03:15,160 Speaker 2: certain kind of iron, and there are many neurodegenitive diseases 52 00:03:15,760 --> 00:03:19,400 Speaker 2: where there is excess amount of this reactive iron that 53 00:03:19,480 --> 00:03:22,799 Speaker 2: causes problem. So knowing that we had a compound that 54 00:03:22,880 --> 00:03:27,120 Speaker 2: targets the iron, that limits the universe of diseases that 55 00:03:27,160 --> 00:03:30,720 Speaker 2: we could go after. Now being a small company, it's 56 00:03:30,840 --> 00:03:34,960 Speaker 2: much easier for us to target a disease like multiple systematrophe, 57 00:03:35,560 --> 00:03:39,320 Speaker 2: for which there are maybe fifteen to fifty thousand patients 58 00:03:39,320 --> 00:03:42,640 Speaker 2: in the United States, versus Parkinson's disease, which is like, 59 00:03:42,800 --> 00:03:45,640 Speaker 2: you know, a million people. So that's a starter. The 60 00:03:45,680 --> 00:03:49,960 Speaker 2: other thing is MSA is a disease where elevated levels 61 00:03:49,960 --> 00:03:53,400 Speaker 2: of iron in the areas of pathology is well established. 62 00:03:53,960 --> 00:03:56,320 Speaker 2: So for that reason and the fact that there's no 63 00:03:56,440 --> 00:04:00,720 Speaker 2: approved therapy for the disease makes it an excellent candidate 64 00:04:01,120 --> 00:04:01,800 Speaker 2: for our drug. 65 00:04:02,880 --> 00:04:06,800 Speaker 1: Okay, and in Layman's terms, how does the drug work, 66 00:04:06,840 --> 00:04:09,600 Speaker 1: then presumably it addresses this iron issue. 67 00:04:10,280 --> 00:04:13,520 Speaker 2: It does. Yeah, So, as I mentioned, there's excess iron, 68 00:04:13,560 --> 00:04:18,520 Speaker 2: and we don't know completely how why there is excess iron, 69 00:04:18,600 --> 00:04:22,159 Speaker 2: but it is an observation that's well established. And what 70 00:04:22,360 --> 00:04:25,960 Speaker 2: the drug does is it really acts as a chaperone, 71 00:04:26,240 --> 00:04:29,599 Speaker 2: meaning it binds the iron inside the cell and it 72 00:04:29,720 --> 00:04:33,279 Speaker 2: helps remove it. It helps it eflux it from the cell. 73 00:04:34,000 --> 00:04:37,440 Speaker 2: Sometimes it can help increase the storage of the iron 74 00:04:37,640 --> 00:04:39,880 Speaker 2: in the cell, or it can help sequester it, so 75 00:04:39,920 --> 00:04:43,480 Speaker 2: it's not causing all these problems. When it's in excess. 76 00:04:43,600 --> 00:04:47,479 Speaker 2: This reactive iron that I'm talking about, it actually causes 77 00:04:48,040 --> 00:04:52,320 Speaker 2: important proteins to misfold and form aggregates, and therefore the 78 00:04:52,360 --> 00:04:55,360 Speaker 2: neurons can't function. That protein that I mentioned is important 79 00:04:55,680 --> 00:04:59,039 Speaker 2: in all neurons and for their function. The excess iron 80 00:04:59,080 --> 00:05:04,640 Speaker 2: itself also is the source of free radicals and observative stress. 81 00:05:04,720 --> 00:05:09,400 Speaker 2: So those free radicals damage DNA and lipids inside cells. 82 00:05:09,760 --> 00:05:12,440 Speaker 2: So by targeting it and kind of getting that excess 83 00:05:12,480 --> 00:05:15,480 Speaker 2: iron out of the way, we hope to preserve neuron 84 00:05:15,560 --> 00:05:20,279 Speaker 2: function and we hope to prevent that oxidative stress thereby 85 00:05:20,480 --> 00:05:22,839 Speaker 2: saving neurons and preserving function. 86 00:05:23,640 --> 00:05:25,839 Speaker 1: I'm learning a lot this morning. We'll be back straight 87 00:05:25,880 --> 00:05:36,159 Speaker 1: after the break. I'm speaking to Dr David Stemla, CEO 88 00:05:36,400 --> 00:05:40,960 Speaker 1: of Alterity Therapeutics. David, we know what it is that 89 00:05:41,680 --> 00:05:45,080 Speaker 1: four three four is doing. Tak me through the clinical 90 00:05:45,160 --> 00:05:46,360 Speaker 1: trials you've been doing. 91 00:05:47,400 --> 00:05:51,680 Speaker 2: Yeah, So what we've done three patient trials over the 92 00:05:51,760 --> 00:05:54,760 Speaker 2: last several years, and briefly I'll talk about the first one, 93 00:05:54,800 --> 00:05:59,000 Speaker 2: which was a natural history study that involved no treatment, 94 00:05:59,040 --> 00:06:03,320 Speaker 2: where we studied our target patients to enroll in the trial. 95 00:06:03,360 --> 00:06:07,480 Speaker 2: And what we learned from that study was which biomarkers 96 00:06:07,520 --> 00:06:11,320 Speaker 2: in which are kind of endpoints to track the target 97 00:06:11,360 --> 00:06:14,640 Speaker 2: engagement and see if we're slowing down the disease. And 98 00:06:14,680 --> 00:06:18,880 Speaker 2: it also helped us refine the criteria for enrolling patients 99 00:06:18,920 --> 00:06:21,320 Speaker 2: into our two treatment studies. So that was a really 100 00:06:21,400 --> 00:06:24,840 Speaker 2: important study to help de risk the Phase two program. 101 00:06:25,160 --> 00:06:27,960 Speaker 2: The next two studies are treatment studies. The main study 102 00:06:28,000 --> 00:06:32,440 Speaker 2: that's ongoing right now enrolled about seventy five patients and 103 00:06:32,480 --> 00:06:35,960 Speaker 2: they were treated with two doses of our drug for 104 00:06:36,600 --> 00:06:42,800 Speaker 2: a twelve months. Now. That study completed patient treatment in November, 105 00:06:42,800 --> 00:06:45,680 Speaker 2: and we should have results at the end of January 106 00:06:45,800 --> 00:06:48,880 Speaker 2: or early February. The other trial that we are doing 107 00:06:49,120 --> 00:06:53,280 Speaker 2: is a similar design trial, except that everyone's receiving active 108 00:06:53,320 --> 00:06:57,160 Speaker 2: treatment and it's a smaller study in advanced patient and 109 00:06:57,320 --> 00:07:00,520 Speaker 2: we got the results from that study in July of 110 00:07:00,600 --> 00:07:03,679 Speaker 2: this year, and that showed us some very encouraging things. 111 00:07:03,760 --> 00:07:07,000 Speaker 2: Number one, it showed that about thirty percent of the 112 00:07:07,000 --> 00:07:10,600 Speaker 2: patients actually had stabilization or improvement of symptoms, which is 113 00:07:10,720 --> 00:07:15,440 Speaker 2: rare in such a rapidly progressive disease. We also showed 114 00:07:15,880 --> 00:07:20,120 Speaker 2: that objective biomarkers that I referred to ones in the 115 00:07:20,160 --> 00:07:23,640 Speaker 2: blood and the spinal fluid as well as on MRI, 116 00:07:24,720 --> 00:07:29,120 Speaker 2: showed that we saw stabilization of these biomarkers compared to 117 00:07:29,520 --> 00:07:32,960 Speaker 2: other patients who were not treated. And I think the 118 00:07:33,080 --> 00:07:37,160 Speaker 2: final important takeaway from that study was that those patients 119 00:07:37,160 --> 00:07:41,120 Speaker 2: who responded had the earliest stage of disease. And that's 120 00:07:41,200 --> 00:07:44,120 Speaker 2: really important because the main trial we're doing is in 121 00:07:44,280 --> 00:07:47,800 Speaker 2: earlier stage patients, so that really has increased our confidence 122 00:07:47,840 --> 00:07:50,920 Speaker 2: and giving us, you know, a lot of optimism going 123 00:07:50,960 --> 00:07:53,320 Speaker 2: into the data readout for early next year. 124 00:07:54,040 --> 00:07:57,480 Speaker 1: Okay, so way too from here. Assuming the data read 125 00:07:57,560 --> 00:08:02,160 Speaker 1: out early next year is promised and enough to put 126 00:08:02,200 --> 00:08:05,800 Speaker 1: you into the next stage of clinical trials, is that 127 00:08:05,920 --> 00:08:07,920 Speaker 1: how it works? You then go into stage three And 128 00:08:08,520 --> 00:08:09,400 Speaker 1: what's that involved? 129 00:08:10,120 --> 00:08:13,800 Speaker 2: Yeah, so there's well, there's two pathways with a positive study. Now, 130 00:08:13,840 --> 00:08:16,160 Speaker 2: if we you know, kind of have a knockout result 131 00:08:16,280 --> 00:08:20,240 Speaker 2: and it's really strong on biomarkers and clinical endpoints, we 132 00:08:20,280 --> 00:08:23,120 Speaker 2: would then go talk with the FDA about getting an 133 00:08:23,120 --> 00:08:26,800 Speaker 2: accelerated approval based on this trial that we're doing right now. 134 00:08:27,440 --> 00:08:30,760 Speaker 2: And that's something that there is recent experience with and 135 00:08:30,800 --> 00:08:34,640 Speaker 2: the FDA is clearly demonstrated and interest in doing that 136 00:08:34,800 --> 00:08:39,560 Speaker 2: for serious diseases like MSA for which there's no approved therapy. Now, 137 00:08:39,600 --> 00:08:42,679 Speaker 2: if we see efficacy but the FDA does not support 138 00:08:43,280 --> 00:08:46,000 Speaker 2: an accelerated approval, we would then go onto that next 139 00:08:46,040 --> 00:08:49,080 Speaker 2: phase that's so called phase three study. It would probably 140 00:08:49,080 --> 00:08:51,600 Speaker 2: be maybe twice the size of the study that we're 141 00:08:51,640 --> 00:08:55,680 Speaker 2: doing now, looking at similar treatments, maybe one to two treatment, 142 00:08:56,400 --> 00:08:58,720 Speaker 2: and we would learn a lot from the ongoing study 143 00:08:58,720 --> 00:09:01,120 Speaker 2: in terms of how the how long the treatment would be, 144 00:09:01,559 --> 00:09:04,080 Speaker 2: what endpoints we've been used, and exactly what kind of 145 00:09:04,080 --> 00:09:06,280 Speaker 2: patients we would want to enroll in that study. 146 00:09:07,160 --> 00:09:10,800 Speaker 1: Okay, so we've been talking about MSI are your learnings, 147 00:09:10,840 --> 00:09:13,280 Speaker 1: I mean maybe the treatment, but perhaps it's the learnings 148 00:09:13,640 --> 00:09:17,560 Speaker 1: potentially applicable to a broader range of illness. 149 00:09:18,280 --> 00:09:21,400 Speaker 2: Yeah, that's really the case, and that's a kind of 150 00:09:21,400 --> 00:09:24,240 Speaker 2: a corporate strategy we've been interested in a long time. 151 00:09:24,800 --> 00:09:28,400 Speaker 2: MSA is a small orphan disease for which there's a 152 00:09:28,400 --> 00:09:32,560 Speaker 2: great need. But we know that that Parkinson's disease in 153 00:09:32,640 --> 00:09:37,960 Speaker 2: particular has similar pathology underlying pathology as MSA. They have 154 00:09:38,640 --> 00:09:42,840 Speaker 2: this protein that misfolds and aggregates the same protein. The 155 00:09:42,880 --> 00:09:46,360 Speaker 2: same happens in Parkinson's disease. We also know in the 156 00:09:46,440 --> 00:09:50,359 Speaker 2: key areas of pathology in Parkinson's disease they get elevated 157 00:09:50,480 --> 00:09:55,680 Speaker 2: levels of iron. So with efficacy demonstrated in multiple system atrophy, 158 00:09:56,120 --> 00:09:58,440 Speaker 2: our next move would be to try and turn two 159 00:09:59,360 --> 00:10:03,400 Speaker 2: Parkinson's disease. That would be the next option. We've recently 160 00:10:03,440 --> 00:10:07,800 Speaker 2: presented some other data basic science data demonstrating we have 161 00:10:08,280 --> 00:10:11,920 Speaker 2: potential use of our drug in another orphan disease called 162 00:10:11,960 --> 00:10:17,360 Speaker 2: Friedrich's attacks, where iron imbalance is a cardinal manifestation of 163 00:10:17,400 --> 00:10:20,000 Speaker 2: the disease and something that we could target with our drug. 164 00:10:20,640 --> 00:10:23,400 Speaker 2: And there are others I will belabor the point, but 165 00:10:23,760 --> 00:10:25,800 Speaker 2: it is clearly a useful target. 166 00:10:26,280 --> 00:10:29,200 Speaker 1: So a ways to go. You have had a long 167 00:10:29,640 --> 00:10:34,320 Speaker 1: distinguished create in medicine in all like in different forms 168 00:10:34,320 --> 00:10:36,520 Speaker 1: of it. You have to be pretty patient, though, don't 169 00:10:36,559 --> 00:10:40,520 Speaker 1: you when you're running a company like this, because ververy high. 170 00:10:40,559 --> 00:10:42,360 Speaker 1: There must be quite a few I don't know where 171 00:10:42,360 --> 00:10:44,400 Speaker 1: the necessary loads, but it just takes a long time. 172 00:10:45,640 --> 00:10:48,400 Speaker 2: You're right, it does. I mean I came to Alterity 173 00:10:48,840 --> 00:10:52,800 Speaker 2: over seven years ago and we picked this molecule, we 174 00:10:52,880 --> 00:10:57,200 Speaker 2: picked this development program. We've done a lot of non 175 00:10:57,240 --> 00:11:00,160 Speaker 2: clinical work, a lot of basic science work as well 176 00:11:00,160 --> 00:11:04,719 Speaker 2: as you know, I'm several studies in healthy volunteers to 177 00:11:04,760 --> 00:11:08,080 Speaker 2: get ready for this stage. In these studies themselves, we 178 00:11:08,200 --> 00:11:12,080 Speaker 2: started in twenty twenty two, So you're right, it is. 179 00:11:12,160 --> 00:11:15,800 Speaker 2: It is a long process, but it's one that you know. 180 00:11:15,920 --> 00:11:18,800 Speaker 2: It's the nature of the beast. You just have to 181 00:11:19,640 --> 00:11:22,320 Speaker 2: you do have to be patient, You've got to be diligent, 182 00:11:22,480 --> 00:11:25,280 Speaker 2: and as I like to say, in addition to my 183 00:11:25,440 --> 00:11:28,360 Speaker 2: role as a CEO as a drug developer, I am 184 00:11:28,400 --> 00:11:31,760 Speaker 2: a serial warrior and I think that's one of my 185 00:11:31,840 --> 00:11:36,120 Speaker 2: personality traits. But I think it causes me and all 186 00:11:36,160 --> 00:11:38,960 Speaker 2: of my team members to pay very close attention to 187 00:11:39,040 --> 00:11:43,040 Speaker 2: detail and give our drug every bit of chance to succeed. 188 00:11:43,600 --> 00:11:45,320 Speaker 1: Good luck with it, David, thank you for talking to 189 00:11:45,360 --> 00:11:45,959 Speaker 1: Fear and Greed. 190 00:11:46,480 --> 00:11:47,760 Speaker 2: Great. Thank you for having me. 191 00:11:48,320 --> 00:11:52,600 Speaker 1: That was doctor David Stamler, chief executive of Alterity Therapeutics, 192 00:11:52,800 --> 00:11:55,320 Speaker 1: a great supporter of this podcast. This is the Fear 193 00:11:55,360 --> 00:11:58,280 Speaker 1: and Greed Business Interview. Remember this is general information only. 194 00:11:58,280 --> 00:12:01,280 Speaker 1: You should always seek professional advice before making any investment decisions. 195 00:12:01,559 --> 00:12:03,840 Speaker 1: Join us every morning for the full episode of Fear 196 00:12:03,840 --> 00:12:06,000 Speaker 1: and Greed, daily business news for people who make their 197 00:12:06,000 --> 00:12:09,640 Speaker 1: own decisions. I'm chanelma Enjoy your day.