Today, we again have CEO Dr. Paul Gavin. I will hand it over to him now.
Thank you, Matt. Good morning, everyone. Thank you for joining today's webinar. My name is Dr. Paul Gavin. I am the CEO of Avecho Biotechnology. I do intend to try and keep this brief, as I know the market opens shortly, but look, t oday, Avecho is announcing the results of our interim analysis for our pivotal phase III clinical trial, which has been testing a proprietary cannabidiol capsule for its ability to manage insomnia. The results are positive, which is obviously huge news for us, with the independent Data Monitoring Board unanimously recommending that we complete the trial to the originally planned 519 patients. This provides confidence that the product is working, which is very exciting both for the company, our partner, and our shareholders.
Today, I will just walk you through what the interim analysis was, what it could and couldn't tell us, and what that means for the company moving forward. This is a very brief refresher on what our phase III trial is and what it is testing, and just so you have a better understanding of the implications. We have been testing a proprietary TPM-enhanced cannabidiol capsule for its ability to manage insomnia. This is the largest randomized placebo-controlled CBD insomnia trial anywhere in the world, targeting 519 patients. This product is being developed for pharmaceutical registration. We have randomized 244 patients for the interim analysis cohort. These are divided loosely across three groups. About 1/3 receive 75 mg of CBD, about 1/3 receive 150 mg of CBD, and about 1/3 receive a placebo. The treatment period runs for eight weeks.
Through that period, participants record how they are sleeping every night, and we assess their sleep using two clinically validated measures. The Insomnia Severity Index, which is a patient-reported assessment of insomnia severity, and Subjective Sleep Efficiency, which is just essentially the percentage of time you have spent asleep in bed. The trial is fully blinded. Participants don't know which arm they are in, investigators running the trial don't know, and Avecho doesn't know either. There are only five people that have seen the unblinded data, and these are all the people associated with the independent Data Monitoring Board, which I will talk about shortly. On the right, just some additional context on the indication itself. Insomnia is actually a huge clinical indication. It is 10%-30% of the population have sleep problems.
Despite being a relatively common indication for the prescription of unregistered cannabidiol products, there are currently no approved cannabidiol products anywhere in the world for the ongoing treatment of insomnia. TGA has a Schedule 3 pathway, which permits over-the-counter pharmacy sales of this product if you're lucky enough to get it approved with the TGA, but n o one has been successful so far. Avecho has set itself up to be the first to get a successful registration and get the very lucrative first commercial mover advantage. Very simply, this is what the interim analysis was. Across 244 patients, we measure whether the CBD capsule is improving sleep against these two pre-specified primary endpoints.
We only need one of the primary endpoints to work, and it doesn't matter which one of them to us, and we won't even know until the end of the trial which one is working. The analysis itself was conducted independently of Avecho by an unblinded statistician. That data was reviewed by a monitoring board, the Data Monitoring Board. This Data Monitoring Board has one international sleep expert, one expert pharmacologist to monitor safety, and one expert statistician. It's those guys that review whether the product's working and then report a recommendation to us based on their review. The DMB could deliver one of three findings. First, which was positive, which was continue the trial, dose another cohort of patients to completion. The second was positive, which was stopping the trial early for efficacy.
The last was the negative outcome, which was stop the trial for reasons of futility. In practical terms for the company, this was a binary event for our insomnia program. Either the drug was proven to be working in the interim analysis, or it wasn't. Our trial had a range of features designed to maximize the chance of success, and I'm just going to highlight these three. The first is these two independent primary endpoints, the Insomnia Severity Index and Sleep Efficiency. The reason we have two is that both of these capture a slightly different angle of sleep. If CBD was going to work one way, we would catch it. If it was going to work the other way, we would catch it as well. Only need one of them to work, don't care which one.
It was essentially we built it to have two independent bites at the cherry. The second piece is this interim analysis. It has an adaptive design feature. A traditional interim analysis tells you whether the trial is working and whether you should continue or stop. Ours also had the ability to recalibrate the trial. If the drug was working, but we determined it needed more than 519 patients, we could increase the patient numbers to meet the new requirement. We could adjust it midway through the trial. Thirdly is the placebo effect. We all knew the placebo effect was going to be the killer of the trial. It's a terrible thing to try and overcome in insomnia trials. Our protocol has multiple mechanisms incorporated to limit the damage of the placebo effect.
We were really comfortable that with all of these design aspects in place, the trial was very rigorously designed in order to really definitively prove whether CBD is doing anything. A bit more detail on these three possible outcomes, and t hese are important to understand because they shape what we can take away from the interim analysis itself. On the left is stopping for futility. This was the outcome that none of us wanted, and this was essentially if the DMB saw that there was no improvement in insomnia scores from treatment with our CBD capsule compared to placebo. If placebo and CBD were the same, they would recommend futility, and we'd stop the trial. The middle one, the base case, is what we were shooting for, and t hat's that we continue the trial with confirmed patient numbers.
In this outcome, the DMB is confirming that there is a difference between a treatment effect between CBD and placebo, and they also confirm the patient numbers required to have a high probability of statistical significance at the end of the trial. Importantly about this aspect is that we had the ability to increase patient numbers, but we did not have the ability to decrease patient numbers. If the drug didn't quite work as well as we hoped, we could include more patients to get statistically significant results, but i f it worked better than we hoped, we didn't have the ability to reduce the patients by more than 519. 519 is the default number. On the right is early stopping for efficacy. This was a new criteria or outcome that Sandoz helped us build. It's a statistical stretch goal.
It's obviously less likely, but there was a scenario that if the trial worked, the product worked unbelievably well, we could stop the trial early for our success. This was the upside, not an expectation. We were very clearly shooting for the middle case. That is essentially what we got. The DMB unanimously recommended that we continue the trial to dose the completed original target of 519 patients. What does this tell us? In meeting the pre-specified criteria for efficacy, we know we have a treatment effect for the TPM CBD capsule versus placebo for at least one of the primary endpoints. I don't know which one it is, I'm still blinded, but we know CBD is working to improve insomnia in this trial so far. Huge sigh of relief for everyone.
The second piece is we know the variability in the data is in line with our assumptions that we originally used to build the trial. If you have huge variability between patients, it's obviously very difficult to show statistical significance. In recommending this outcome, they have confirmed that the variability is in line with our assumptions. What this means is that if the second cohort of patients behaves like the first cohort of patients and we complete the trial to 519 patients, the trial is very well-positioned to meet its primary endpoint and achieve statistical significance. Huge de-risking event for us.
The very interesting piece, if you look deep into what this means, is that by not recommending that we dose additional patients, the DMB have confirmed that our expectations or our assumptions that we made for this product performance are at worst in line with our expectations, or possibly much better because we didn't have the ability to reduce patients. Where that is great news for us is that when we modeled the trial, our expectations was that this product would behave at a similar magnitude to commercial insomnia drugs. By virtue of telling us to go to 519 patients, we are being told that to date, to date, the magnitude of effect is in line with commercial insomnia medicines, which is obviously a huge outcome.
The safety piece, obviously, safety is also a key concern of the DMB, and we did not see a single serious adverse event across the entirety of our program. We weren't expecting to because CBD is a relatively benign molecule. Very, very heartwarming to hear that no serious adverse events, and the safety profile of the capsule is very good across the 244 patients. Where this is very interesting is now when you think about this in the insomnia context, because insomnia drugs worldwide are known to have a raft of quite unwanted side effects. So, d ependence, tolerance, withdrawal, next day impairment is one of the major ones, so you can't drive or operate heavy machinery the next day. Overdose toxicity. Insomnia drugs, medications have historically been one of the first things people use to try and commit suicide.
You cannot kill yourself with CBD, so there's no overdose risk there. Complex sleep behaviors, risk in older adults. The takeaway here is that the product safety profile is very competitive with the improved insomnia drugs. Really, when you roll in the efficacy and the safety signal that come out of this DMB recommendation, it changes how we think about everything. We've been thinking for years now or wondering, our central question has been whether our product works. The interim analysis has changed that and how we approach it. From here on in, the planning for the business is that the assumption that it does work. This really shifts our focus towards commercialization and how this product gets positioned against the medicines people are currently relying on for their sleep.
As you heard, many existing prescription medicines carry well-documented limitations, next day impairment and the risk of overdose being the big ones, and these are concerns that cannabidiol's safety profile does not share. That is huge when it comes to product positioning. The insomnia market is large and growing. There are a number of products vying for this market. Avecho has now a safety gap that we can very, very explicitly exploit. We also have an open OTC pathway in Australia encouraging products like this to get registered with the TGA, which is a huge commercial advantage. If we are successful, we'll have the first mover for the local market. That could be worth hundreds of millions a year. We are in a spectacular position after this interim analysis.
A treatment that can improve sleep without safety burden has a clear place in the market, and it will be central to our ongoing licensing discussions. For those of you that are new to the story, we managed to license the commercial rights to Australia for this product last year to Sandoz, which was a huge coup for us. Sandoz are the perfect partner, and so far, they have proven in every way to meet those expectations. We are working very closely with them. We love them. We are going to do very well together, taking this product into Australia. The first deal is always the hardest, and n ow that it is done, we have the commercial validation from a large multinational pharmaceutical company. Now, we also have positive interim analysis data from a pivotal phase III clinical trial.
We really do expect the licensing discussions now to ramp up. Australia is a first step. It is commercially lucrative, but it still remains one of the smaller global pharmaceutical markets. It is still a very important benchmark, as you can extrapolate the terms that we got for the Australian market over to the overseas deals. We are currently in discussions for various territories around the world with many interested parties who have just been sitting back now waiting to see the interim analysis results. I will be very happy to call them on Monday and tell them that the product signal is good, and we can start talking. That is all the exciting bit. Back to, I guess, the job at hand. Now that we have to dose an additional sort of around 300 patients, how do we fund it? How long does it take?
The priority to fund the trial will be through pharmaceutical licensing deals. As I say, there are a number of people at the table. This is how we got the trial, the product to where we are now, where Sandoz put in money to get to the interim analysis. We have pro forma AUD 6.2 million already in the bank. I am not in need of capital immediately. I do not intend to immediately run out and do a capital raise. I have time to execute on these deals, and get things funded that way. How will we accelerate? We are realistically ready to start dosing again in the coming months.
There is some red tape that we have to tick up after the interim, then we can start dosing with the existing sites that are on our trial, and then the intention is to open 10 additional sites once we get the additional money through the door. With those 10 additional sites open, we are very comfortable that we can smash through these remaining patients in about 12 months. We have learned a lot of lessons about the recruitment rate and how to get these patients, and with 10 additional sites, very comfortable that 300 gets eaten up very, very quickly. What runs in parallel? It will be a very exciting time in parallel. TGA dossier, we will start working on that. We will obviously be doing manufacturing and getting all that ready. The big thing will be licensing deals.
We would be very comfortable to expect multiple licensing deals, which obviously everyone gets excited about, for different territories. Really, the new piece is engagement with overseas regulators. So, the FDA. I will run over to the FDA in the back half of this year, and have a chat because, in the past, probably kind of thought that the FDA would be one of the later regulatory jurisdictions to tackle, but a t the moment, they have a President Trump. Most half of the FDA have gone, so they're less experienced. He's signed an executive order to legalize cannabis. He's also signed an executive order that the FDA should approve products on a single phase III rather than two phase IIIs.
My U.S. regulatory firm has advised me I need to get in front of them as quick as physically possible because there may be a scenario where we can ram this product through the FDA much quicker than we had ordinarily been anticipating. This is just the immediate path forward. This is the next sort of 12- 18 months. The back half of this year, we would expect to pursue multiple licensing deals, which will help fund accelerating the trial. As I say, we've got sufficient capital in the bank already to maximize the value of these deals. We don't need to be pushed into anything. We'll bring on additional sites, we'll engage with the overseas regulators, and manufacturing scale continues. Around those licensing deals and all this kind of stuff, there'll be a lot of very exciting news for the shareholders and investors.
Through 2027, we'll pursue further licensing deals. The work here focuses on completing the phase III clinical trial, which is obviously the jewel in the crown in any inflection point for a biotech, phase III study completion. Manufacturing, TGA dossier compilation and we'll look to try and submit that, as soon as we can. Then, we'll be developing the product in other territories. Additional countries overseas may require additional work for their territories, so there'll be news and outcomes around additional work happening overseas. Look, the interim analysis was a clear go, no go point for the company. Beyond it sits a very clear sequence of work, that takes the program to TGA submission, approval, commercialization, multiple licensing deals for additional territories, and further development in more lucrative territories. Many of you will likely buy in today and sell out next week.
Those of you that buy in for the bigger picture should see a sequence of incredibly valuable inflection points coming over the next one to two years, and we will not be a AUD 50 million market cap. Just quickly, I stole this slide from last month's AGM, i t might be a bit out of context here, but really, it's a bit of back slapping for us. For years, we've made the case for a very specific thesis, and at every step, those assertions have been validated by an external body. We set out to demonstrate that we could build a product with better absorption than other CBD products, and the independently generated preclinical data overseas validated that. We made the case that our product was unique, novel and inventive, and the United States Patent Office validated that.
The European Patent Office has allowed it, and now, Japan's allowed it as well. We claimed that our trial design and submission strategy was the right approach for the unique Australian OTC opportunity, and the TGA validated that, telling us that our trial was well thought out and robust and they had no recommended changes. We told the market that the data we generated, the trial, the commercial case, would be of interest to a major pharmaceutical partner. We licensed Sandoz, the largest generics pharmaceutical company in the world. Put money on the table at risk before data was even available from the phase III trial. We remained confident that this story was strong, and if we set the right expectations and continued to deliver, the market would listen. Our market cap's gone up four times in 12 months. Institutional investors are now on the register.
Euroz Hartleys have initiated independent research coverage. The market is now validating story, and we expect that to amplify further after today's announcement. Every assertion that we have made about this program has been independently validated. There was only one prediction left, and that was essentially that our product has any signal for efficacy in the indication that we chose. Although the study is not yet complete, final outcomes obviously can't be determined until then, w e are more convinced than ever after this positive interim analysis that our CBD capsule works as a treatment for insomnia. Last slide, if it ever turns over, I've got the spinning wheel of death, essentially, I guess the next piece to the story is biotech sentiment is really low right now. There's been a sequence of unwanted outcomes that nobody's wanted. Investors are risk averse. They're hesitant to invest.
The sector has been needing a win. Our interim analysis is a big win, significantly de-risking our product, our phase III clinical trial, and our company. The investment thesis for us is now clear. We've got a positive interim analysis in a pivotal phase III clinical trial for insomnia. This does not come around every day. It significantly de-risks the remaining phase III trial. While the trial still needs completion, we're moving forward with the assumption that the product works for insomnia. We have a very clear near-term regulatory pathway with the TGA, offering a unique over-the-counter CBD opportunity, which is unique in the world and lucrative. The commercial opportunity in Australia is large. 9.5 million Australians have sleep problems. The addressable market will be above $120 million per annum. The opportunity for the rest of the world is even bigger.
Sandoz has already licensed the Australian rights, putting money on the table, $3 million up front. Largest pharmaceutical generics company in the world has backed this product. We have discussions for additional territories across multiple regions. We expect those to proceed to closure now the product is and the trial have been de-risked, and we have money in the bank. Again, I do not need, I do not have any plans to immediately raise capital. I have time to do deals. Those of you that are going to sit back and wait and think that you can come in on a capital raise, it's not happening. You're going to have to come in and buy on market if you want a piece of this. Really, the last line, I just wanted to emphasize, someone mentioned it to me yesterday, and it stuck in my head.
We've been thinking for a long time about if this will work, and now we know. Now, we have to start thinking about just how big this could be, because both the product and the company could be huge. With that, I thank you for your time. Matt, I'll pass it back for any questions.
Thanks, Paul. Yes, just as a reminder to everyone, if you have a question you'd like to submit, use the Q&A function within Zoom, and we'll jump to those now. Paul, first off, can you give us an idea of how long the new client testing, as someone's put it here, or the new cohort will take to set up and the process, et cetera?
The setup will be in two phases. We can pretty rapidly jump into dosing of patients through our existing clinical trial network. Potentially, we're dosing in a couple of months. As I said, there's some red tape that we have to tick off with ethics before then. We'll open the remaining 10 sites once we've consummated some deals, which we hope will be in the next short period of time as well. Overall, we're modeling that we finish the phase III trial by the end of next year. The trial, we're probably thinking costs about AUD 15 million, the remaining part of the trial, which is still very, very cheap for a global phase III clinical trial. As a reminder, we got AUD 5 million upfront just for the commercial rights to Australia.
A couple of these deals in the overseas territories pay for the rest of the study.
Thank you. Someone's asked a simple one about what was Sandoz's response on the results.
Look, obviously everyone's excited. I mean, the thing that I'm eternally grateful to Sandoz for is they're a generics company, and generics companies don't typically invest at risk in products under development. But they did because they could see the commercial opportunity, and we've been in bed with them for a year. We talk to them every week, project committees, updating them on manufacturing and clinical timelines. Everyone's invested, and yeah, no, they were very pleased.
The next question is, were you told what the study is now statistically powered for, percentage wise?
No. We remain blinded, so there's only so much that the DMB can tell us. All they can tell us is that we need to complete the trial to 519. As I said, by definition of the criteria, that means our product is working, at worst, as well as we powered it to be or at better, more than that. But yeah, we don't have any further information within that gap as to what it should be.
Next question, in this study, what is the magnitude of the effect Avecho is trying to measure or the magnitude of the effect that would be clinically relevant?
Clinical significance and statistical significance are different. We were using similar reductions in the Insomnia Severity Index and some of these other metrics that lemborexant in the ISI SUNRISE 2 trial did. That was a couple of points reduction in ISI. I think they had about a seven-point reduction from baseline.
Thank you. The next question is, can Sandoz agree to a license deal with you for another territory?
Sandoz has first right of refusal to the rest of the world. Yeah, look, we'll be discussing, obviously, additional territories with Sandoz, but also additional, d on't get me wrong, 100% there'll be countries that are of no interest to Sandoz, and there'll be countries that are potentially of keen interest. The product adds value to all the jurisdictions around the world, and really, we'll partner with the best partner for any specific geography.
While we're still on Sandoz, someone's asked, does this event see any further milestone funds come in?
No, it doesn't. The milestone payments triggered by our agreement don't take effect with an interim analysis.
Next question is someone just asked around patent protection, if you just want to give a summary on that.
Yeah. Patent protection is perfect. You cannot get patent protection specifically on cannabidiol because it is of botanical origin, but w hat you can protect is a unique formulation. Because our formulation incorporates our own TPM technology, we built a very bespoke Swiss watch, which is our TPM combined with cannabidiol, with a couple of other ingredients to increase the absorption. That patent protecting that product was granted in the U.S. recently, so that's got protection out till 2043 in the U.S. It's been allowed in Europe, so over the back end of this year, we'll start going through a grant through the individual European countries, and it's recently been allowed in Japan. Patent protection for the product out to about 2043.
Next question is, will you look outside Australia for additional participants?
This is a very good question, and this is something that we're looking at. This depends on partners. There are specific geographies that will happily accept a TGA submission, and be okay with that. There are other territories for a regulatory submission that would ideally like their own citizens to be on the trial. Part of the conversation we're having with a couple of prospective partners is you license country X, and we'll open some clinical trial sites in your country so that we can get some of your citizens onto this phase III to make it more acceptable for a regulatory submission. It's definitely something we're considering. It'll depend on who's partnered for where.
Next question is it possible we can get to market in the U.S. prior to the next trial results?
Prior to the next trial results, no, we'll have to finish this phase III trial, if that's the question, before we can get it registered as a pharmaceutical anywhere. The possibility with the U.S., which is new, is that maybe we can get it registered with the FDA off this single phase III trial. I was a bit concerned when I heard this, that we weren't dosing any Americans, and so whether the FDA would like it. Our U.S. regulatory firm have told us the Australian population is demographically similar enough that the FDA will accept Australians, so they weren't concerned about that. That'll be one of the questions we ask the FDA. Is there any additional work that the FDA requires in addition to this phase III trial, that they would need to see before a regulatory submission there?
Will the placebo run-in be as effective for the second cohort, given there has been some disclosure on this being part of the trial?
I'm not really concerned about placebo run-in affecting the second cohort. It's not documented by me anywhere. Anyone, look, truthfully, the people that come onto our trial are in the older demographic. Avecho is not even advertised in all the clinical trial material. You have to look pretty close when you're inquiring about the trial to work out Avecho's involved, and then you'd have to do some due diligence and trawl through a whole bunch of webinars. Given the age demographic of most of the people on the insomnia trial, I'm not concerned that a significant percentage of those are doing sufficient due diligence to work out about the placebo effect.
The question is, just to confirm, the final phase III clinical trial likely reads out at the start of calendar 2028. Is that correct?
We're trying to run it as fast as we can. At the moment, we're modeling that we finish the trial the back end of next year. That's what we're targeting. Back end of next year, whether it slips into the year after, we won't know until we start. I should say, like, with 10 additional sites, we only need a couple of them to perform well, and we will eat into these 300 patients very, very, very rapidly. Even as an example, of the 244 that we have now, over 100 were dosed by a trial site in Sydney that only came on in July. They did 100 patients between July and February, one site. If we get 10 new sites, and we're continuing that existing site, we get 10 new sites and they pull their weight, 300 will disappear quick.
Couple more to go. If Sandoz has first right of refusal and someone comes in with a proposal for better economics in a region, do you still have to give it to Sandoz?
Oh look, the way the first right of refusal will be is I'll have to negotiate some terms with company X. Once we're happy, we would ordinarily accept those terms, I have to present that to Sandoz. Then it's up to Sandoz to decide whether they want to match those terms and take the product for that territory or pass.
I believe you touched on this. What is patent protection for China? Someone has asked.
China, it's not granted yet. It's going through China. It's going through a whole bunch of countries. As you can probably tell by when I said patent life out to 2043, it was only submitted a couple of years ago, so it's new. It's going through prosecution in all the major territories now.
All right. That's all the questions. Thanks to everyone for your interest and attendance. We've had a bit over 200 people online, so clearly a lot of interest. Paul, I'll just hand it back to you to provide a closing comment.
Oh look, I don't know what else to say, really. You work a very, very, very long time for a phase III trial. We've set the whole thing up so well. We've got the best partner. There's this commercial opportunity in Australia with the TGA that's unreal. We've got this product with increased absorption and patent protection. It was all set up for this one unknown, which was, is there any signal that this product works for insomnia? We have it now. So now, finishing the trial is more procedural for me than anything else. The company, the product, everything is significantly de-risked, and t his is a hugely, hugely exciting time for the company. I'll be running around doing a victory lap for the next few months.
Thanks, Paul and thanks to everyone for joining, and we'll look forward to bringing you more.
No worries. Thank you.