Gavin, and I'll hand it over to him now.
Just as a brief refresher on what our trial is and what it's testing, we are testing a proprietary TPM-enhanced cannabidiol capsule for its ability to manage insomnia. This is the largest CBD insomnia trial anywhere in the world, targeting 519 patients. As of this moment, we've randomized 244 patients for our interim analysis cohort. They're divided across three arms. About a third of patients will receive nightly doses of 75 mg of CBD, another third will receive a higher dose of 150 mg, and another third will receive a placebo. Treatment runs for eight weeks. Through that period, participants record how they're sleeping every night, and we assess their sleep using two clinically validated measures. The Insomnia Severity Index, which is a patient-reported questionnaire which assesses insomnia severity, and sleep efficiency, which measures the percentage of time patients actually spend asleep while in bed.
The trial is fully blinded. Participants don't know which arm they're in, investigators who are running the trial don't know which arm they're in, and I don't know which arm they're in. The only people who will see unblinded data when the time comes are an independent statistician, who will conduct the interim analysis, and our independent Data Monitoring Board, who will review it, and you'll hear a bit about the DMB today. This blinded nature is how we ensure the integrity of the result. Just on the right-hand side, some of the additional context around the indication itself. Huge clinical indication, 10%-30% of the population. CBD itself, despite insomnia being a common indication for the prescription of unregistered CBD products, there are no registered CBD products anywhere in the world for the treatment of insomnia.
There is now an opportunity in Australia with the TGA, where they have incentivized drug development by allowing oral CBD for insomnia to be registered as an over-the-counter medicine. One of those drugs that you don't have to pay to see a GP, pay to get a prescription. Direct access to the entire adult population whenever they need it. This was announced in 2021 by the TGA, to date, there has not been one single product that has been successful, we are really setting ourselves up to be that first product and get the first-mover commercial advantage in Australia, not just with us, but with our partner, Sandoz. This trial has really been designed and conducted initially with this TGA opportunity in mind. The interim analysis in very plain language.
Again, across these 244 patients, we measure whether the CBD capsule is improving sleep against two pre-specified primary endpoints. The interesting or the important thing is each endpoint, we only need one of them to work. This is not one of those trials that's built with needing two. We only need one of these endpoints to work, and it will be a successful trial. The analysis itself will not be conducted by Avecho. As I say, it's conducted by an unblinded statistician who, by definition, has had nothing to do with the trial, nothing to do with the company. They have to be fully independent. They will conduct the analysis and pass the data across to the Data Monitoring Board. They receive it, review it against the objectives of the trial, and then they will deliver a recommendation to the company based on their review.
The DMB will give us one of three recommendations. Two are positive, one's negative. The one that we're shooting for is that the DMB comes back to us and says, "Yes, the trial is working, and you need to continue it to completion with another 519 patients," or however many that is. At that stage, we'll have a confirmed sample size. They will say, "Yes, you need this number of patients." The second is, "Stop the trial for reasons of efficacy." In this scenario, the trial will have worked so well that we are highly statistically significant and can stop the trial successfully after 244 patients. The third outcome, which is the negative one, is to stop the trial for futility. Despite our best efforts, CBD in our product, in our trial, has not proven to be working for insomnia.
In practical terms for the company, this is a binary outcome for the insomnia program. It's not a binary outcome for the company. There's still obviously a lot left in the company and even this product. This will decide whether insomnia is right for this product moving forward. Essentially, either it'll prove that the drug is working or it isn't, and we're going to have that answer in a few weeks, in late June. This is, I guess, the sequence from where we are now to the result. These first three steps are now complete. Recruitment's finished, dosing's finished, database is locked, and the statistical analysis is currently underway. Very stressful/exciting time. The remaining steps are once this statistical analysis is complete, it gets handed across in June to each of the members of this Data Monitoring Board.
They will all review all the data independently by themselves, and then later in June, they will all come together and convene to discuss their thoughts and deliver a consensus recommendation to Avecho. Avecho will not be present at this meeting. As I say, this all happens completely blinded behind closed doors. Once we have this recommendation from the DMB, we'll obviously announce this directly to the market. Again, late June is the target. The DMB itself, it's composed of, as I say, external experts. By definition, they can't be involved with the company. They can't have had any input with the trial. They can't benefit in any way with a recommendation that's positive or negative. All completely independent. On that DMB, we have one sleep expert who's an international key opinion leader in sleep.
His function is obviously to look at the sleep results of the trial. We have an independent safety pharmacologist. His main job is to make sure that the product is safe and there are no side effect profiles that are of concern. To date, we have had not a single serious adverse event, which is amazing. The third one is an independent expert statistician. The three of them, between them, will make the recommendations. That's truthfully standard best practice for a pivotal phase III clinical trial. Now, the trial itself, why this trial is positioned for success. We've talked about it a few times, I guess. We have designed every feature into this study to maximize the chance that it will give a positive outcome. There are three design features that sit above everything else in importance.
I've talked about them all before, but just to reiterate here, two independent primary endpoints. The reason we have two is that the Insomnia Severity Index and sleep efficiency capture different angles of sleep. If CBD works one way, we'll catch it. If it works the other way, we will catch it. Again, the way we've built the trial, we only need one of them to work. I don't care which one it is. As long as one of these works, the trial is a success. We get two independent bites at the cherry. Second is this interim analysis, which is built with an adaptive design feature. Quite often, an interim analysis is just there to tell you whether the trial is working and you continue, or it's not working and you should stop.
Our interim analysis allows us to recalibrate the trial halfway through. Essentially, the statisticians will look at the difference that we see between the treatment and the CBD, sorry, the CBD and placebo for these insomnia measures, and they'll look at the variability, and they'll say, "Based on these observable features, you need to dose 519 patients to complete the trial successfully." Or they can actually tell us to increase the patient numbers. We can adjust the patient numbers we need halfway through the trial to make sure the trial is conclusive and we hit exactly the patient numbers that we need for statistical significance. Very powerful inbuilt cheat code to maximize the chance of success. The last bit, though, is obviously placebo effect.
You've all heard me for many years talk about the risk of the placebo effect and how damaging it is to these trials. Essentially, we know everyone will improve. Everyone on the trial will improve, even when they don't take CBD, because patient-reported outcome trials like insomnia or pain or anxiety always have patients improving on placebo. The art is specifically to design the trial in such a way that you limit the damage of the placebo effect. We have a number of mechanisms in place, and we will share them once the data is all complete, but very comfortable that we are ticking all the boxes to minimize the damage of the placebo effect. There are other things as well. Each and all of these are additional value adds. Maximum allowable dose of 150 mg for this OTC opportunity.
As I say, the largest insomnia trial in the world for increased power, eight weeks of treatment duration. Very tight inclusion criteria, so you've got to score at least 15 or greater on the ISI to be a part of our trial. It's been built with the FDA and the European instructions on insomnia trials. All of these improve the odds further. It's timely to remind you that when the TGA reviewed our clinical trial design, they described it as well thought out and robust, and they had no recommended changes. We are comfortable that we have built this trial appropriately to maximize the chance of success. The three possible outcomes. Important to highlight, this is our base case. The one in the middle is what we are aiming for.
Essentially that the DMB tells us the trial is working, you need to continue the trial with a confirmed number of patients. The base case will be a total of 519. In that scenario, if they tell us that, we know there's a different between the treatment and placebo, we know there's an acceptable variability, and we know that if that variability and difference continues for the second cohort of patients, the trial will be statistically significant and be successful. This is what we have always been shooting for, and it is what is the most likely. Now, this one on the right, as I say, you haven't heard as much about because it's newer. It's an upside. It is essentially early stopping for efficacy.
This is what I mentioned earlier, that the drug/trial are working so well that they're highly statistically significant, and we can stop after 244 patients. Now, this is a newer feature to the trial because Sandoz built it. Sandoz have helped us, their clinical teams, over the last period of time to build this additional feature. As I say, this is an upside. By definition, early stopping for efficacy is statistically unlikely. It's much less likely than this. Obviously, for everyone, either of these two outcomes are enormously positive for the company. On the left is the one that we don't want. That's futility.
That's essentially that the DMB looks at the data and says, "There is no difference between the treatment group and the placebo group." In which scenario we won't dose any more patients, we'll preserve shareholder capital, realistically, we'll look for a new indication. This will be the death of the insomnia program. It won't be the death of the product or the company. You have to understand, CBD is currently being examined for many, many indications at the moment, including pain, arthritis, anxiety, menopause, all of these kind of things. Our product has increased absorption, patent protection, pharmaceutical dosage form, GMP stability. It will add immense value to any of those indications that CBD ultimately gets proven to work for. It just may be that we may prove that sleep is not one of those. That's the framework.
As I said, this is the one we believe is the most likely outcome, and it is the one that we are shooting for. If we achieve that, obviously, the next question that you will all ask is, how do we fund it and how long will it take? We've done very well recently, in the context of we had options exercised, we had R&D tax credits come back. I have got a good amount of cash in the bank to get me to this interim analysis and well past it. It is not enough money to fund an additional 300 patients, should we need them. With a de-risk program, a phase III trial that's working, I will have the luxury of choice. I have zero concerns about where this extra money will come from.
The priority, as was with Sandoz the first time, will be a pharmaceutical licensing deal. This time it'll be for the big, expensive overseas territories. An upfront licensing fee for one or more territories will be used to fund the rest of the trial. This could be Sandoz expanding global coverage, or it could be another company. I have no promises from anyone, but I have a lot of very interested eyes sitting there waiting for the result of this interim analysis. Should those pharmaceutical deals take a bit longer to execute than possible, I always have up my sleeve that I could do a placement as an alternative. I have plenty of time to consummate a pharmaceutical licensing deal rather than do a capital raise.
Essentially, as I say, with a positive trial under my belt, I will have the luxury of choice. The timing. When money is not an object and you have some incentivized large pharmaceutical companies that want to complete trials as fast as possible, you open more sites. We have already identified about 10 additional clinical trial sites that we will open and engage on the trial. The minute we push the button, they'll start running as fast as they can. The modeling that we have done with Sandoz suggests that if we do need another 300 patients, with the sites that we have and some of the existing sites that are already on our trial, recruitment will be over and done within about 12 months.
I hear everyone saying, "It took two years to do 244 patients." With 10 additional sites and all the lessons learnt over the last two years, we're very comfortable that we get this done in 12 months. What happens, everyone, I can hear you all saying, "Oh, a year, another year of trial." It's a year of trial that everyone understands is working. During that time, we will be building, or Sandoz will be building the TGA submission dossier. It's TGA's responsibility to submit to the TGA. We will be completing all the manufacturing scale-up for that submission, and very comfortable that you all get lots of exciting news along that journey of licensing deals for overseas territories. The newer piece to this as well is obviously the moment this works in June, there's potential conversations to have with overseas regulators.
I had emotionally thought that the FDA would probably be one of the last countries to fall just because complicated regulatory environment. Cannabis is illegal over there federally. FDA typically wants two phase III clinical trials. We recently met with our U.S. regulatory firm, so they came out to Australia. Essentially, their new guidance to me is that the FDA has lost, under the Trump administration, a significant percentage of their experienced staff. Trump has legalized cannabis, and Trump has written an executive order for the FDA that they should start approving products on a single phase III trial rather than two.
The guidance from my U.S. regulatory firm is that I am now in this unique window in history, and while the FDA is weak, after a positive result in June, I should run over there as fast as I can and see what it will take to ram this through FDA approval much quicker than really I've been thinking was possible. That's going to be a lot of exciting news for everyone. Assuming success in June, this is really just the bullet point immediate path forward. We've talked about this to death. This is the way the DMB will work. I will know late June, which means you will know late June. H2, we'll see licensing deals. Very comfortable that H2 would see licensing deals with a successful readout in June.
As I say, we've got sufficient capital in the bank already to ensure we have the time to maximize the value of these deals. We also have prospective partners who are incentivized to move fast. We'll bring additional sites online. Dosing will recommence. As I say, we'll engage with overseas regulators, and we'll continue on the manufacturing. Through 2027, the work focus is on just finishing everything, finishing the phase III trial, finishing the manufacturing, finishing the TGA submission, and then letting Sandoz get to this, to the TGA as fast as possible. Really, the interim analysis is the gateway, and beyond it sets a very clear sequence of work that takes the program to TGA submission and approval. Last slide, which I have stolen from my AGM tomorrow. It's a bit out of context.
It might not make as much sense here, but it's essentially the closed-door story that started five years ago. We have been saying, this company's been saying, made a case for a number of years, how amazing this product and this opportunity is. It just seemed to me that at every step, those assertions that we have made have been validated by independent external party. We set out to demonstrate we could build a product with better absorption than the other CBD products on market. The preclinical work that was conducted overseas validated all of those claims. We said that the product was unique, and it was novel, and it was inventive. The USPTO validated all those claims when they granted our patents.
We claimed that our trial design and our submission strategy were the best that we could do and were uniquely suited for this Australian OTC opportunity. The TGA, we met them, they validated it. They told us that it was well thought out and robust, and they had no recommended changes. We've been telling you all for years that with our trial design and our product and the commercial business case, we would find a large pharmaceutical partner. Sandoz, the largest generics pharmaceutical company in the world, validated that last year, signing a 10-year commercial partnership and putting AUD 3 million on the table at risk, which they never do. They're a generics company. We've remained confident the whole time that this story was strong, and if we set the right expectations and continued to deliver, the market would eventually listen.
Our market cap has increased four times in the last 12 months. We think that's just the start. We've now got institutional investors on the register. Euroz Hartleys have initiated independent coverage. The market is now validating our story, and we expect this to amplify beyond a nice announcement in June. Every assertion we have made about this program has now been independently validated, and there is just one left, and that is that our product works for the indication of insomnia, which we chose. That validation is going to arrive in less than five weeks, so the clock is ticking. Look, with that, thank you for your time. Matt, I'll pass back to you for any questions.
Yeah, thanks, Paul. If anyone has a question they'd like to submit, please do so by typing it in on the Q&A function within Zoom, and I'll jump into those now. I'll start with the ones that are, I guess, directly relevant to today's presentation. First one I've got is, post the interim readout under the current trial design, can you open up trial sites in other jurisdictions to potentially allow for approval in those other jurisdictions? Would this then help licensing deals in those other jurisdictions?
Yes, yes, and yes. Yeah, we can. There's a number of things that we can potentially do with a second cohort of patients. The decisions on what we do with the second cohort of patients will very much, to that question, be sort of a result of the parties that end up partnering on the product.
Thank you. The next question I have is, has Avecho had any pre-submission meetings with the TGA to ensure all requirements are met?
We have met with the TGA. TGA generally doesn't do meeting. I mean, they're not the FDA. They don't do your pre-INDs. They're not overly helpful. The difference here is that the TGA and the Australian government are desperate for one of these products to succeed. I mean, you've probably all heard me talk about it a lot. The reason why there's this Australian OTC opportunity is because of how uncomfortable the Australian government and the TGA are with medicinal cannabis. They've incentivized pharmaceutical drug development by saying, "If you prove this works, if you get it registered with the TGA," they would allow it to be registered as an over-the-counter medicine.
The reason they've done that is because the minute a product is registered with the TGA, it becomes illegal to prescribe a similar product through the Special Access Scheme and the routes that medicinal cannabis is using. They're trying to drag unregistered products kicking and screaming onto the registered medicines list. The government and the TGA are desperate for one of us to succeed. A bunch of companies ran for this opportunity. They all failed, because they were medicinal cannabis companies that have never done drug development before. Now that we are the last one standing, TGA asked us to come in. We met, went in in 2024. We ran them through everything, all the data we had to date, preclinical, clinical, CMC, manufacturing, phase III protocol, submission strategy. As I say, their eventual opinion was well thought out and robust. No recommended changes.
Thank you. The next question is, what is the price per dose expected to be?
Price per dose is to be determined. Sandoz will obviously be the company at the end of the day that determines pricing. It has to obviously compete commercially in an OTC space. There are only two OTC sleep medications at the moment that this will be competing with. One is RESTAVIT, which is antihistamine, which is only available for short-term use, and the other is melatonin. In Australia at the moment, melatonin is just low dose. It can technically only be dispensed to people over 55 years of age. The nice thing about melatonin is that it's a Sandoz product. Sandoz will just be positioning this product versus that. I guess you can rest assured that Sandoz are the world's largest pharmaceutical generics company, and their mission statement is to make medicines affordable for everyone. This will be priced competitively.
We just don't know what that price will end up being yet. There's no way Sandoz commercializes something that can't be sold.
Thank you. Two-part question here. Do you have any objective measurements or is it all self-reported? How does this stack up versus melatonin?
This is all subjective measures. Essentially when we built the trial, we built it using the FDA and the European guidance documents for insomnia. The FDA specifically mandates, historically, two separate individual phase III clinical trials. One has to be fully subjective, which is our trial. It has to be patient-reported outcomes. The second trial is objective. The gold standard for FDA objective trials are polysomnography. That's where you go into the sleep clinic and you wear all the electrodes. It's not actually even representative of your normal sleep. When we went to the TGA, we actually did have some objective measurements on our trial. We had some of these new fancy wearables.
The TGA just looked at us and said, "Look, you're welcome to do the objective data if you want, but we are going to ignore all the data that comes from it." At the moment in time, there are no wearables that are validated for an FDA or TGA submission package. None of them are quite there yet. The use of a wearable on our trial cost AUD 1 million. Yeah, we took it off, given that it had never been validated for TGA or FDA submission and it cost AUD 1 million.
Thank you. The next question is, have U.S. pharma firms also shown interest in partnering?
I've spoken to firms in all corners of the world as of this stage. Everyone, for the most part, acknowledges the value of what the product could be. There's interest in a range of different countries. Now I just have to wait and pass through this interim analysis, and then it'll be a much more exciting pressing conversation.
Thank you. Someone's also asked about accessing a copy of the research that you mentioned. I'll put that in the chat here, but I can also say that's in the Investor Center on the website and on Avecho's social media for anyone who's looking for that. Next question I've got is, "Can you please explain the further preclinical validation point on slide page 17?
Sure. We ended up developing the product initially across four countries. We started in Melbourne, obviously started in our labs, and then went over to Monash Institute of Pharmaceutical Sciences, who in their labs showed that our TPM, our technology, would increase CBD solubility in the stomach. We went over to Denmark, where there's some experts over there, and they optimized our formulations further and showed that not only they reproduced that result and showed that CBD would have increased gastric solubility and absorption when combined with TPM. We optimized that product, and eventually we did our final sort of preclinical work over in the U.K. Which is not in this deck, but in the world at the moment, there is only one FDA-approved CBD product. It's a product called EPIDIOLEX for rare childhood epilepsy, and it's the only one.
It did all its preclinical work at a lab in the U.K. from a company called Labcorp. We gave Labcorp our formulations and our TPM, and they did all the same tests that had been done on EPIDIOLEX, and they proved that our product had a four times increase in absorption compared to the only FDA-approved CBD product on the market. All of that work was done independent of us, on three separate occasions. three separate independent groups confirmed that our TPM would increase the absorption and solubility of CBD.
Thank you. The next question is there anything else which can be modified under the malleable interim analysis design other than patient numbers for the balance of phase III?
No, not a major design feature. Essentially, the more changes that you do, or not even just changes, the more things you examine and the more things you change at an interim analysis costs you alpha. Alpha is basically the statistical currency that you've got to spend at the end to prove something is statistically significant. We only have repowering, but we can potentially One of the things, to one of the earlier questions, that we are examining is whether we did take a subset of our remaining 300 patients and put a wearable on them just for markets that might want some comfort around an objective measurement.
Thank you. Next question is, did the other peer companies which had failed insomnia trials in Australia meet with the TGA? If they did the TGA have any changes to the trial design?
I have no idea. None of them have announced or reported any TGA interactions or the conversations that they had. I cannot imagine a scenario where the TGA would've told them that their trial designs were good, because none of their trial designs were good.
Thank you. Can you also give some more color on the epilepsy trial where sleepiness from CBD consumption was found to be a side effect of the drug?
Yeah. As I say, there's just this one FDA-approved CBD product called EPIDIOLEX. It's for rare childhood epilepsy. They obviously did randomized placebo-controlled phase III trials to prove that CBD would work for sleep. Also when you do your big randomized placebo-controlled trials, you obviously inherit a whole range of side effects that have to go onto your product label. We are doing exactly the same thing. The most common side effect of CBD that they found on their trial was sleepiness. The doses of EPIDIOLEX were making people sleepy. They have already proven in phase III clinical trials that CBD will work to affect your sleep. Have to say straight up in the outset, the dose of EPIDIOLEX is higher than us, our dose.
We are not trying to actually look to make people sleepy either, because if you're looking to make people sleepy, then you inherit potentially labeled warnings around next day impairment, and that's actually going to be a key commercial feature of the product. Most of the sleeping medications currently on market have what's called a black box warning. Their label insert will say, "Do not drive, do not operate heavy machinery," which is actually a big-ticket item, especially in the U.S. and Europe, around insurance and patient reimbursement. If we don't make people sleepy, then we don't inherit that warning, which is a key commercial feature.
Thank you. A couple more questions still. Is Avecho concerned about the TGA consultation about the medicinal cannabis market?
Oh, that is the greatest thing in the world. No, not concerned at all. I'm a cheerleader on the sideline. Essentially, what is most likely is that when we work in June, when we get a good result in June, we will become the weapon that the TGA uses against medicinal cannabis. You have to understand that medicinal cannabis flies in direct opposition for what the TGA is actually there for. TGA is there to ensure the Australian population have medicines that are proven to work, proven to be safe, proven to be manufactured appropriately, and medicinal cannabis is doing none of those things. This is why the TGA's incentivizing everyone to try and do drug development. I will be the TGA's best friend.
Yeah, I'm very comfortable with the TGA making it as hard as possible for medicinal cannabis because it won't affect me at all, and it will drive more patients to this product.
Last one I've got is, has Avecho considered or does it plan to consider using its CBD for other indications such as anxiety beyond, sorry, beyond insomnia?
Very definitely. As you heard me say, CBD itself, it looks like quite a useful molecule across a whole range of potential future indications. I didn't mention in this deck, but our primary indications are around insomnia, but we have secondary indications around anxiety. We're already looking at anxiety. We know patients have had some positive results with osteoarthritis, symptoms of IBS, IBD. Another one I'm really interested in, because insomnia plus anxiety is essentially menopause. Huge opportunity in menopause. There's opportunities everywhere for this product. Once we get over this first hurdle, there's a number of things. With that in mind, the thing that we talk about a lot is that Sandoz looked at this product and went, "We want first right of refusal for the rest of the world." Like, okay.
They also have first right of refusal on additional indications. Sandoz like the idea of additional indications. Yeah, that's definitely on our to-do list.
Thanks, Paul. I'll hand it back to you just to provide a closing comment.
Oh, look, as I say, it's a great story. I know it's a great story. You know it's a great story. It's been many years in the waiting now but the result is so close that we can touch it. Everything has gone correct so far because we've designed appropriately, we've built the product appropriately. We have a huge market opportunity. We have the best commercial partner we could've hoped for. We have a clear TGA regulatory pathway with a product that has patent protection out till 2043. Huge exciting time. I don't imagine I'm an AUD 50 million company much longer if this result works in June, and we will be a very different investment opportunity for everyone. Again, thank you for your time and, yeah, watch in June.
Thanks, Paul, and thanks to everyone for joining today. If you've got any questions, obviously there's details on the screen there. Thanks again.
Thank you.