ACTINOGEN MEDICAL LTD (ACW) - Revolutionizing Mental Health Treatment: CEO Steve Gourlay on Breakthrough Xanamem Drug, Phase 2 Trial Success, and Future Implications

What if controlling a single hormone in your brain could revolutionize the treatment of Alzheimer's and depression? On this episode of ASX Briefs, we're joined by Steve Gourlay, CEO of Actinogen Medical, a trailblazer in biotechnology, to unveil how their groundbreaking drug, Xanamem, could be a game-changer for mental health therapies. Steve takes us through Actinogen's fascinating journey from their 2014 merger with a University of Edinburgh startup to the promising Phase 2 depression trial results, where 167 patients showed significant improvement with minimal side effects.

Steve demystifies the complex science behind Xanamem, explaining how it targets brain cortisol, a hormone infamous for its role in stress and cognitive decline. With a deep dive into the biology of the brain, Steve enlightens us on how selectively reducing cortisol in regions like the hippocampus and frontal cortex can prevent the detrimental effects of chronic stress on nerve cells. This episode is a must-listen for anyone interested in the future of mental health treatment and how innovative therapies are set to change the landscape.

Transcript

Andrew Musgrave Host

00:01

Welcome back to ASX Briefs, and today we're joined by Steve Gourley, the CEO of Actinogen Medical, which is a biotechnology company pioneering novel therapies to address major neurological and neuropsychiatric diseases, with a particular focus on Alzheimer's disease and depression. Steve, thanks for joining me today and welcome to the ASX Briefs podcast. 

Steve Gourlay Guest

00:23

Thank you, Andrew. Thanks for having me.

Andrew Musgrave Host

00:24

Okay, now there's plenty going on at the company, but for those who don't know too much about Actinogen Medical, do you just want to give us a brief overview of who the company is? 

Steve Gourlay Guest

00:33

Sure. So Actinogen is actually a merger with the University of Edinburgh startup called Corticrine. That was merged into Actinogen as a shell in 2014. And since then, it's been doing a series of clinical trials to develop a really potentially revolutionary new therapy for depression and Alzheimer's disease, and so, as is common in drug development, it takes a while. 

00:55

However, we're now in that exciting period of mid to late-stage clinical trials where we've actually got good evidence that the drug is working validated the target, which is reducing cortisol in the brain, and so our next focus is really to continue enrolling our Alzheimer's trial and then move forward with another trial in depression. 

Andrew Musgrave Host

01:16

Okay, and the company has recently shared significant positive results from your XanaCIDD Phase 2a depression trial. So, can you explain the key findings of this study and how these results will help shape the plans moving forward? 

Steve Gourlay Guest

01:29

Now, depression trial was a quite a reasonably sized trial with 167 people who had to have at least mild to moderate depression and a degree of foggy thinking on a test called a coding test. 

01:41

So essentially these are fairly heavily pre-treated patients, most of whom were actually on another antidepressant just to sort of set the scene. And despite that being a very difficult group of patients to treat, we saw clinically and statistically significant improvements over placebo in the Xanamem treated group for depression symptoms that measured in a few different ways. So, this is very exciting because it establishes the drug and the cortisol mechanism as a bona fide antidepressant mechanism and the safety of the molecule is really excellent. So, unlike a lot of antidepressants that have lots of side effects such as sexual dysfunction or feeling blah, we don't have any of that profile as far as we can tell, at least in the first 400 or so patients that we've treated. So, we did also look at cognition and interestingly, the placebo group. Well, Xanamem group did improve in their cognition, but so did the placebo group. So, we essentially defined that well, figured out that cognition really does improve as depression improves. But our drug is primarily an antidepressant and that's really good news because it's an exciting opportunity clinically and commercially. 

Andrew Musgrave Host

02:49

Okay, and Xanamem's mechanism of controlling brain cortisol is central to its potential. So, can you elaborate on how controlling cortisol levels can address cognitive decline in diseases like Alzheimer's and depression? 

Steve Gourlay Guest

03:03

Yeah, so the biology of the brain is very complicated, so I'll try and simplify it as accurately as I can. And cortisol has been associated with depression and known to be associated with the onset and risk for Alzheimer's and its progression for decades and decades and decades. However, nobody's ever had a drug that gets into the brain and selectively controls the tissue production of cortisol in the local areas of the brain where the enzyme that we target is expressed, such as the hippocampus and the frontal cortex, which are essential for memory and the way you can think. And so, really, we have the only molecule that's ever been able to test the hypothesis the cortisol hypothesis, if you like. Does controlling levels of this hormone in the brain, cortisol work? Now, what is cortisol there for? 

03:53

Well, cortisol is needed in the body to maintain normal cellular function. It's part of the stress response it's often called the stress hormone, actually and what it does is, when you're being attacked, for example, and your adrenaline goes up, your cortisol goes up, pumped out by the adrenal glands, and it's really that sort of fight or flight reaction. So, it's quite stressful, if you like, but necessary in order for your muscles and your body to fight the intruder. For example, however, chronic levels of stress in the brain are not good for you. In fact, if you take a pellet of cortisol and do an animal study where you actually look at putting cortisol into tissue, it actually directly causes dieback of nerve cells and the local tissue. So, cortisol is toxic, so essentially toxic chronic stress is bad for you and what we've shown in our depression trial is that indeed, if you bring that cortisol down in the tissue of the brain, you do get improved depression symptoms. 

Andrew Musgrave Host

04:53

Okay, and the XanaMIA Phase 2b Alzheimer's trial is also underway. So, what can you share about the progress and what are some of the key milestones we could expect in the near future? 

Steve Gourlay Guest

05:04

Yes. 

So, this is a very important trial for us because it's designed using the data from our previous analysis which showed in biomarker positive patients in the Phase 2, these are patients with mild Alzheimer's disease diagnosed clinically but not with any biomarker or scanning to confirm the diagnosis. -positive patients in the phase two. 

05:16

But in biomarker-positive patients we saw a really big Xanamem effect to improve this global score called the CDR Thumb of Boxes, which the FDA and other regulators use for approvals in Alzheimer's disease, and indeed, if you extrapolate the results from that previous trial, it would be several times better than the new antibody therapies that have recently been improved in the US Cordylochembi and Kinsunla. So, we've now designed this trial to treat exactly the same patients, patients with mild to moderate Alzheimer's disease but they have to be biomarker positive with a simple blood test, and this blood test is a new sort of revolution in Alzheimer's and it's only been around for the last few years, but it's highly validated. So, by choosing biomarker positive patients who are fairly likely to progress during the nine months of the trial, we can then see whether Xanamem is significantly better than placebo, and hopefully it will be several times better than any known other therapy, as suggested by the previous data. So, it's a very exciting trial. 

06:22

We started in Australia. We've enrolled quite a few patients at this point and we're opening US sites as we speak and expect enrolment to accelerate, with interim results in the middle of next year and final results about a year later. 

Andrew Musgrave Host

06:37

And the company has secured funding through to the mid-2026, which is a strong indicator of your financial health. So, can you discuss how you plan to allocate these resources to maximise the development and commercialisation of Xanamem? 

Steve Gourlay Guest

06:49

Yeah, we're very fortunate to have been supported by our shareholders several times in the last 12 months. Unfortunately, clinical trials as economically as we do them in Australia, with the assistance also of a fairly large R&D tax credit, which is going to be $9 million this year, which is a major contribution to companies, small companies like ourselves, yes, trials cost money. So the new funding is to fully enrol the Alzheimer's trial, to also beef up the quality supervision and statistical supervision of the trial in a way that designs it as a pivotal trial, meaning one that the FDA would use as one of two pivotal trials to approve the drug, and that brings forward the potential year of approval by a year or two and overall it just improves the integrity and credibility of the final results. So, it'll be 220 patients in that trial and the funding sees us through well towards the end of 26 and beyond. 

Andrew Musgrave Host

07:51

Okay, and just to wrap things up, the company has now reached a transformational stage in clinical development. So, what are some of the company's key strategic goals over the next two years? 

Steve Gourlay Guest

08:01

Yeah, probably the best way to answer that question is to answer the partnership question, because I get this a lot and there are two sweet spots in drug development for partnerships. The first is preclinical, when you're in the animal study stage when a big company like an AbbVie or a Merck might want to get their handle on a target and maybe a suite of molecules that could approach that novel target. So that's one in the sweet spot. The next sweet spot comes where we are now and that's mid to late-stage clinical trials, because typically the big pharma partner wants to have a major say in exactly how the phase three is designed, because they want to use those endpoints and the information in those trials for the label and eventually, of course, for the marketing of the drug when it gets approved. And so late phase two, early phase three, which is exactly where we are with both of our programs, is that sweet spot for partnering. 

08:55

Now I don't want to oversell the ease of which you can well, which you can partner. It takes a while, but we do have very good relationships with all of the potential pharma partners who are very interested to see the depression data and understand more about our program. So, we will continue to pursue that actively. But the new funding sets us up to go all the way to the end of the Alzheimer's trial independently and that gives us a strong bargaining position so that we don't have to accept an inferior deal from any of these companies. 

Andrew Musgrave Host

09:25

Okay, Steve. Well, it's been great to get an update on the company. Plenty going on. So, we wish you all the best and we look forward to further updates in the upcoming months. 

Steve Gourlay Guest

09:33

Perfect, thank you. 

Andrew Musgrave Host

09:36

That concludes this episode of ASX Briefs. Don't forget to subscribe and we look forward to catching you on our next episode.