Actinogen Medical Limited (ASX:ACW) CEO and Managing Director, Dr Bill Ketelbey talks about Xanamem, XanaHES trial and potential partnerships.Cheers. Thank you Clive and thank you everyone for joining in. Yes, as Clive says, ASX listed company developing a range of compounds associated with cortisol inhibition. Cortisol inhibition in the brain and raised cortisol is associated with cognitive impairment in various neurological and metabolic diseases. And our lead compound, Xanamem.
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Our lead compound, Xanamem, has been shown to be a very effective compound at inhibiting cortisol production and enhancing cognition. This is a novel mechanism of action. It's a brain penetrant compound, very importantly, the drug has been designed specifically to get into the brain, inhibit the 11β-HSD1 enzyme. This enzyme is associated with the activation of cortisol in every cell in the body. But in the brain, there are particular areas where it's particularly highly concentrated. We've got very good proof of concept data from animals and humans on our drug and a very good safety profile. We've now dosed some 200 patients with our drug. Safety's been good. We've got an excellent pharmacokinetic and pharmacodynamic profile demonstrating that our drug gets into the brain, inhibits the enzyme in the brain, and suppresses cortisol and enhances cognition. So in summary, Xanamem, an oral brain penetrant, selective and infective inhibitor of the 11β-HSD1 enzyme with a strong safety profile.
And with the next slide, thank you, I'll tell you more about why cortisol is such a key target.
Over the years, it's been recognised in numerous conditions associated with raised cortisol. As people age normally, cortisol increases. People with diabetes, schizophrenia, epilepsy, depression, all of them are associated with raised cortisol. All of them are associated with cognitive impairment. And with Alzheimer's disease in particular, it's quite clear now from the evidence that as cortisol rises, it's associated with the development and the progression of Alzheimer's disease. And the hypothesis behind our drug is if we can find a way to suppress that cortisol production, we can find a way to manage cognitive impairment and potentially even Alzheimer's disease.
There are numerous publications across the literature. This slide just reflects some of the data. On the left-hand side, a graphic showing you between normally cognitive people and those with Alzheimer's dementia. A demonstration of cortisol rising and the same paper from a very large study in Australia demonstrating that as people age normally and as cortisol rises, there is an increased risk of developing Alzheimer's disease. In fact, what the study has shown is that 50% of people aged 65 and over have raised cortisol. So the hypothesis behind our drug to inhibit that cortisol in the brain is what underlies the development of Xanamem.
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So the recent data that we have that has particularly excited us is reflected in this slide. On the left-hand side, the XanaHES trial where we dosed an elderly healthy population, 42 subjects at 20 milligrams a day, demonstrated the drug was safe, demonstrated that it inhibited cortisol very effectively, but also very pleasingly showed a good, strong, robust efficacy signal, showed an enhancement in cognition. And this is at 20 milligrams a day.
This data sits alongside the XanADu trial where we used 10 milligrams a day and demonstrated that while we inhibited the cortisol and 10 milligrams a day was safe, we didn't hit the efficacy endpoint, the primary efficacy endpoint we expected. And what these two data sets demonstrate to us is that perhaps in the XanADu trial, the dose was not correct and this is further reflected and further demonstrated and I guess reinforced from our target occupancy study that is very near complete. Now, all of these studies are being collectively analysed.
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Are being collectively analysed and the output is going to define the future studies that we're about to implement.
Just some of the data from the XanaHES trial. On the far left, you can see the column of domains, memory domains and cognition domains that were evaluated. In the middle, the p value demonstrating a clear statistical effect seen in three of the six domains. And on the right-hand side, the treatment effect from that study. Now, for those of you unfamiliar with the p values and treatment effect, what we've shown is a statistical significance for the top three but importantly, a very strong treatment effect demonstrated with our drug in this population. Any treatment effect above a 0.2 is a demonstrable treatment effective, above 0.5 a good treatment effect, and above 0.8 a strong treatment effect. What we're demonstrating here is our drug has an effect at week four, all the way out to week 12. A good strong, consistent treatment effect.
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Demonstrates this very elegantly graphically where you can see by week two, we were already showing a separation of the curves, a demonstration of cognition that was sustained out to the end of treatment at week 12.
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And a study that we were running concurrent to this was a target occupancy study where we took a radiolabelled drug. We gave a radiolabelled drug to a cohort of patients. That drug binds to the enzyme and in the top line of images you can see the enzyme very actively bound. That same patient then was given 20 milligrams of Xanamem daily for seven days. And then the radiolabelled tracer was re-given to the patient and you can see in the lower image quite clearly the Xanamem was binding to all the binding sites with very little ability for the tracer to bind, demonstrating target occupancy, demonstrating that our drug gets into the brain and effectively binds to the enzyme in the brain.
We've done this now across, in fact, 32 patients. The 32nd patient just in fact completed this morning and demonstrating between a 50 and an 85% occupancy in the brain across a dose range between five and 30 milligrams daily. So very effective, efficient demonstration of the occupancy of our drug to the binding sites in the brain. A good demonstration of our drug working exactly as it's been designed.
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So where we are now. We've got good breakthrough results from the XanaHES trial at 20 milligrams a day, demonstrating good cognitive enhancement in healthy elderly patients. Good target occupancy data. Our drug binding to the enzyme in the brain between five and 30 milligrams. Good evidence across 10 and 20 milligrams of cortisol inhibition, exactly as designed for our drug and a good safety profile across the 10 and 20 milligrams.
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So all of this data, as I've said, is being collated and analysed with the intent that the output from this will help with designing and informing the studies going forward.
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And going forward, we're undertaking this comprehensive review and we have already strategically identified a number of studies that we plan to implement with really the flag bearer being mild cognitive impairment in Alzheimer's disease. Our next Alzheimer's disease study going forward. The key opinion leaders and relevant regulatory authorities are being involved and we're speaking to big pharma, providing all the data to them and demonstrating the progress we're making and our plans going forward.
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Demonstrated here where as I said, the lead indication that we plan to initiate is mild cognitive impairment in Alzheimer's disease. We have two other studies under planning in well advanced cognitive impairment in schizophrenia and diabetes. And in fact, a fourth study where we're undertaking the feasibility and it is looking a very strong contender as well. But really, today is about MCI in Alzheimer's disease.
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And that's demonstrated here. Mild cognitive impairment is, as reflected in this slide, the very earliest indication of Alzheimer's disease. The first time somebody presents with cognitive impairment with risk factors demonstrating the potential that they will develop Alzheimer's disease but before they are what demonstrably part of what is defined as mild cognitive impairment, which is the population that we studied in the XanADu trial at 10 milligrams a day.
As you can see on the left-hand side, studied at 20 milligrams was the healthy elderly population in XanaHES and mild cognitive impairment sits very elegantly between these two studies and that's why it is it the obvious next population for us to research. This is the goal of all Alzheimer's research, all pharma companies to identify and develop a drug that treats mild cognitive impairment because these are the patients that'll be most responsive to therapy. As the disease progresses down mild, moderate, and severe, the patients are losing more and more neuronal load and are much more less susceptible or responsive to therapy. So the earlier the disease can be diagnosed and the earlier the disease can be treated, the better. And for us, this is a perfect opportunity to demonstrate that, having shown great efficacy in healthy elderly. The next step is to move one step along into mild cognitive impairment.
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So this is just a reflection of the size of the opportunity. 8% of 65 year olds are affected by this. Huge number of patients in the US. There's no currently available therapy for it. And quite honestly, if you add raised cortisol on top of this population, you're at an even greater risk of developing Alzheimer's disease. So a huge population and an easy population to define to be able to test our hypothesis for suppressing cortisol and enhancing cognition in a mild Alzheimer's disease population.
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Just the size of the opportunity is demonstrated in this slide here. Well over US$10 billion of potential in sales if we can demonstrate efficacy in this population. And this just reflects the large markets around the world. Current therapy provides only limited benefit. There is no benefit in mild cognitive impairment and as such, it's a huge opportunity, huge unmet medical need ready for us to enter and exploit.
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So in summary, the investment summary of what I was presenting to you, Xanamem a differentiated compound. A novel mechanism of action differentiated from all other drugs under development for Alzheimer's disease. A good strong safety profile and a very good robust efficacy signal demonstrated at 20 milligrams daily in the XanaHES trial, endorsing the cortisol hypothesis that underlies the development of our drug.
The next clear obvious direction for us to move into is mild cognitive impairment, a population that sits right alongside the healthy elderly population and a population as yet without any current therapy and a population desperately needing some therapeutic to help in the management of this population and potentially in the slowing down of the development of the progression of the Alzheimer's disease into mild Alzheimer's disease and further.
As I say, mild Alzheimer's disease is not the only indication. We have other indications under development but MCI in Alzheimer's disease is the key one we're taking forward. We've got good evidence from the XanaHES trial, good optimised study parameters around dosing from our target occupancy study. We're speaking to partners and big pharma companies and demonstrating the elegant data that we've produced. They are very interested in what we're doing and very interested in watching our progression going forward into the initiation of the MCI study and the production of the results.
We had hoped to initiate the study in 2020. Quite clearly Covid, as it happened with all biotech companies, has slowed down our plan somewhat but we are working aggressively towards hopefully initiating the study, if not late this year then certainly early next year. A huge opportunity, huge unmet medical need, and a huge opportunity for investors to come on board for the journey with us in this very exciting area of research.
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Just to reflect on any questions or for more information, my contact details are on the slide. Please contact me. I'm sure I can answer any questions you may have. And with that, thank you very much indeed for joining me today and thank you Clive.
