IRLAB Therapeutics AB (publ) (IRLABA) Earnings Call Transcript & Summary

Pharmaceutical Company IRLAB, transforming life for people with Parkinson's and other CNS disorders have closed its book for the third quarter in 2022. We will now be giving the presentation of the company and reported quarter, followed by a Q&A session. Viewers can also ask their questions in the live chat. Participating from the company is CEO Richard Godfrey, Nicholas Waters, who is Executive Vice President of R&D; and CFO, Viktor Siewertz. So with no further ado over to you Richard, the stage is yours.

Thank you, [ Mattias ] and good morning. Welcome to our Q3 presentation from IRLAB. Firstly, may I draw your attention to our disclaimer and our forward looking statements made in this presentation. So the purpose of today's agenda is to give an update on the quarter and our business operations, to provide an overview of IRLAB and also to run through updates on our R&D and financials. But specifically what we'd like to do in this presentation is give a thorough review of our clinical programs and offer some guidance on the anticipated top line data from mesdopetam trial which we anticipate at the end of this year. So during the quarter, my first operational quarter as CEO, we really did make very solid progress on our clinical, pre-clinical and research projects. In July we announced that we expanded mesdopetam Phase II trial to 154 patients. And in September we confirmed that recruitment was complete. So we have a high level of confidence that there should be top line data available at the end of this year. At the same time our partner Ipsen initiated 3 clinical pharmacokinetic studies which will provide data to support later stage clinical development. We continued with our ambition to raise our profile and we're very visible at multiple events during the quarter. And there was an increase in our share capital related to the acquisition of the know-how for one of our research projects. Our finances remain in good order. We had a modest sales of SEK 16 million related to our ongoing business relationship with Ipsen. Our operating costs in the quarter were SEK 40 million, in line with previous quarters and we closed the quarter with a very strong balance sheet, SEK 292 million. So our balance is -- our finances are in good shape. We slightly increase the number of -- in our organization as well by adding someone to our R&D group. So, in a snapshot what is IRLAB? IRLAB is a clinical stage biopharmaceutical company. Based on really deep and profound understanding of Parkinson's disease out of the University of Gothenburg and the research by Nobel laureate Professor Arvid Carlsson. Today, our activities are very focused on developing novel first-in-class treatment for patients with Parkinson's disease. Our technology, our products and the business case with our products is truly validated by the license that Ipsen has taken for our lead program mesdopetam. We remain in control of for unencumbered assets that we continue to develop through clinical development, each one with blockbuster potential. And our organization remains very well positioned, very experienced team, strong balance sheet and listed on that Stockholm Exchange. So for those who are not familiar with Parkinson's disease, here's a quick recap. It's a chronic and progressive neurodegenerative disease with no cure. It's characterized by these cardinal symptoms, rigidity specifically in the morning, postural instability, bradykinesia and tremor, and it's all caused by a loss of brain cells that produce a chemical, a neurotransmitter called dopamine that has a pivotal role in controlling how the brain regulates movement. And you can see on the right here how the little dots are dopamine and how they facilitate communication between the neurons or the brain cells. Dopamine is also lost from other parts of the brain that you can see in this sketch, in blue and green and gray, and indeed also from other parts of the body. But we're fairly focused on enhancing the symptoms that otherwise patients would suffer from. We've included this slide for those who are not that familiar with the disease, and I do not intend to go through it line by line. But what we can really understand is, why it happens? Why it's important? The patients that are usually affected by it, the fact that it's driven by environmental factors and some genetic factors. But really, what I'm focusing on is the fact that the current standard of care, a drug called levodopa is quite effective, but not without limitations. And indeed, there is no treatment available for one of the most troublesome symptoms of Parkinson's disease and that's postural instability and falls where we think we have a solution with pirepemat. The trouble with Parkinson's disease and the standard-of-care levodopa is, whilst it works very well in the early stages, as illustrated by the black box in the chart here, what we can see is after maybe 3, 4, 5 years, this actually becomes quite intolerated and we have this breakthrough dyskinesia, which becomes quite a problem for the patients. And indeed, as the disease progressive becomes more and more of a problem. This is the found -- sorry. Parkinson's disease remains a disease with growing incidence, maybe 6 million people in 2015, maybe 9 million people today, an estimated to be 12, 13 million people by 2040. A few years ago the BMJ, the British Medical Journal, published the top 10 priorities for treating and caring for patients with Parkinson's disease. And what we can see on the right here, they include things like number one, impaired balance and increased falls frequency, cognitive decline, motor complications, the levodopa-induced dyskinesias and non-motor symptoms such as psychosis and anxiety. And what we can see on the right here are the therapeutic attempts that IRLAB is having to address these treatment priorities for these patients. This is the foundation for our pipeline. We're developing a portfolio of therapeutics to treat patients with Parkinson's during their disease journey. We know in the beginning patients are greeted with bradykinesia, rigidity and tremor. We're seeking in our research program to develop a one-a-day program to address this. After 5 years or so, as I just mentioned, bradykinesia breaks through levodopa-induced dyskinesias and psychosis. And mesdopetam program is aimed at addressing that. A few years later patients start to suffer with cognitive decline and apathy and our research programs 942, 757 are designed to address that. And possibly one of the biggest problems is postural instability, loss of balance, increased fall frequency and pirepemat is designed to address that. So we really are developing a suite or a portfolio of therapeutics to really help the Parkinson's patient during that disease journey. And all of this is possible because of our unique and proprietary research engine ISP. This uses advanced systems biology, phenotypic screening, and machine learning to inform our chemists on how to design, develop the optimal drugs that are going to address these symptoms with molecules of the best biological fit. This truly does allow us to deliver first-in-class molecules with very strong patent protection. And that what we're seeing is increased probability of success going through the stages of clinical development. And with that introduction, I'd like to hand over to Nicholas to give you an R&D update, specifically on our clinical programs. Thank you, Nicholas.

Thank you, Richard for that introduction. And I will now go through some information which we've shown before on mesdopetam. And mesdopetam is a drug designed to treat dyskinesia. As Richard pointed out, this was one of -- is one of the biggest problems in the treatment algorithm for Parkinson's disease today. And as pointed out earlier, levodopa is the mainstay treatment for all -- most Parkinson's patients across the globe today. 40% of all patients entrap into the state of dyskinesia and that occurs around 4 to 6 years after the introduction of levodopa, according to the literature. The number of patients are quite large. We see more than 1 million patients across the different regions on the globe which have this problem on a daily basis. And the patient population we are targeting in our clinical development of mesdopetam, which we are pursuing in partnership with Ipsen, are patients who have what's called good ON-time, that is when levodopa works well, during the day. About 6 hours of that day. And then 6 hours of what is called bad ON -- bad ON-time, which is ON-time with dyskinesia, which of course hampers quality of life a lot. And the objective for our mesdopetam program is to reduce the bad ON-time as much as possible for these patients, by converting bad ON-time to good ON-time. The molecule discovered using our ISP technology is designed to treat dyskinesias. It does so by inhibiting a dopamine receptor called dopamine D3, discovered in the 90s actually. This is a molecular receptor which acts erratically in response to levodopa after chronic treatment in animals, but also in humans, of course. And mesdopetam has the ability to inhibit the excess dopamine produced by levodopa in the wrong places of the brain, and doing so reduces dyskinesia. And we have shown in pre-clinical studies that mesdopetam has a clear and highly efficient antidyskinetic effect, but also a non-psychotic property at the same doses. And in specific assays we also see cognitive improvement which could be associated with D3 antagonist effects of mesdopetam. We have pursued a clinical development program to get to the final product with mesdopetam. Starting with Phase I studies, singular ascending and multiple ascending doses in healthy volunteers. Couple years back, we discovered there that the drug is tolerable, has good PK properties and a safety profile which is acceptable. We went on to do a small Phase Ib study in Parkinson's patients in Scandinavia. We also there could conclude that mesdopetam can be safely administered to patients with Parkinson's disease, and advanced stages of Parkinson's disease. These are very severe patients that we're looking at in this Phase Ib study. We also got a signals of efficacy on the scales that were used in that study showing an antidyskinetic effect while leaving normal levodopa -- the wanted effects of levodopa working. So there we had some kind of guidance towards a larger Phase IIa study which we conducted a couple of years back. A larger study, which we mainly pursued in the U.K., double-blind placebo controlled study, where we looked at a number of different doses and the effect of levodopa. We also conclude from that study that the molecule is tolerable in this population, a good safety or safety profile and we also saw very clear efficacy on the dyskinesias, and especially improving daily good ON. We could see somewhere between 2 and 3 hours of improvement in good ON, which is -- has not been seen in any study before. We are now conducting a Phase IIb study which Richard alluded to. We will conclude that study during the winter and we'll have top line data at the turn of the year. This study is powered -- sufficiently power to detect effects which are clinically relevant in this patient population. For the further development into Phase III and eventually marketing, Ipsen has all the rights and, of course, all the decision making to do around this program. Looking back at the data from the Phase IIa study, once again we could clearly see a reciprocal improvement in good ON, on the expense of bad ON across the different doses in the study. So going from 2.5 milligrams to 7.5 milligrams, a clear increase in good ON at the expense of reduced bad ON, which is the one that effect. Higher doses does not increase the efficacy which is not surprising given the literature around the D3 receptor and bell shaped dose response curves in a number of assays. So what we've done in the Phase IIa is basically define the dose range that we're using in the Phase IIb conducting right now. And we have also built on the safety and adverse event profile database. And what we've learned is that the side effect profile of mesdopetam is basically on par with placebo as far as the Phase IIa study goes, illustrated in the table at the bottom here. So the current study is a ongoing study, is a 4 arm study, placebo and 3 different doses, fixed doses of mesdopetam. We are looking at a 3 months treatment period, which is 2 months longer than previous trials. And there is a 1 week follow-up after cessation of treatment. And we are looking at the primary endpoint as good ON-time through reduction of bad ON-time. Some guidance on the expected outcomes of this trial. Of course, there is a long list of endpoints that we are analyzing post database lock and analysis. However, all that cannot be collected in in one chunk, so what we expect to be able to produce as early as possible with the information around the top line results is, the primary endpoint of course changing daily hours of good ON without troublesome dyskinesia. That is the primary endpoint. We will discuss the significance of this effect. They are statistically significant and also the clinical relevance of this effect. And the full account of the study will be presented at medical congresses during the Spring of '23. To give some background to clinical relevance we have put together as a table here, just illustrating what recently approved drugs in this space have been able to produce. Most drugs that are developed for Parkinson's disease are targeting good ON. Good ON is the endpoint for any improvement in the treatment of Parkinson's disease. And as you can see in this table, there are a number of compounds here which have been approved based on around 1.5 hours of improvement in a good ON. The thing here is that, all these drugs they collect the improvement in good ON from reducing Off time. And as you can see in the graph, Off time comprises around 4% in this specific -- in our specific population that we are targeting and that's less than the 6 hours of bad ON which these patients suffer from. So with mesdopetam, we intend to change bad ON-time to good ON-time as said before. While all the other drugs approved to-date, except for amantadine, I'll come to that, reduce Off time. Even as little as 0.7 hours have been approved in the recent filing. And there are a number of formulations of levodopa. And levodopa in the pipeline right now there are 2 programs where they were submitted NDAs, improving ON-time with about 0.5 hour or up to 2 hours -- 1.7 hours roughly. The improvement in good ON that these drugs and treatment strategies have is -- comes also with problems and that is increased -- in most cases, an increased incidence of dyskinesia, which we are trying to treat with mesdopetam. So in this context mesdopetam sticks out quite a lot with converting bad ON-time to good ON-time, instead of converting Off to good ON-time. Amantadine, a drug which has been used since the early 60s as a treatment for Parkinson's disease, is also -- also has antidyskinetic properties. It combines effects on Off, reduced Off-time about, 1 hour with reduced peak levodopa dose dyskinesia by around 1.5 hours. So, in summary if one looks at the documentation published around 2, 2.5 hours of improvement. So there you have the background data which illustrates what is clinically relevant and also acceptable to regulators. Talking about amantadine, of course, we've done comparisons and in pre-clinical assays, we can see that mesdopetam actually has a better effect than amantadine on dyskinesia. And also a very clear dose dependent effect while the effect of amantadine, at least in animal models, is quite abrupt at high doses. And as Richard pointed out, we also have this program out licensed where we are working together with Ipsen to develop this compound to a final product. And we have completed one of the largest deals in Swedish biotech history around this asset. Moving on to pirepemat, it's a drug which is -- as Richard pointed out, it's designed to improve balance and reduce falls in Parkinson's disease. We are currently running a international placebo controlled Phase IIb trial and this is a wholly owned asset. Reducing falls is one of the greatest medical needs in Parkinson's disease. Roughly 45% of all individuals diagnosed with Parkinson's fall on a regular basis. That's a couple of times a month. And then the reason for falling can be many, of course, but in principle it correlates very well to the cognitive decline occurring in the later stages of Parkinson's disease. So the cognitive decline leads to impaired balance and falls which leads to injuries and costs. And the consequences of falls in this population are quite severe often with fractures and hospitalization. Hospitalizations are quite costly, also both for the individual who has fallen, but also for society. In the U.S. a cost -- a fall injury costs around $30,000 to treat. And this the market for or the patient population, I should say, eligible for a treatment to improve balance is quite large, larger than the dyskinesia population worldwide. The mechanism underlying pirepemat effect on cognitive function, but also on -- as a consequence on falls and balance lies in the frontal cortex. And pirepemat was designed to specifically activate pathways and neuronal activity in the frontal cortex which are hampered in Parkinson's disease, relating to norepinephrine and dopamine transmission, but also a acetylcholine transmission. Pirepemat has a radio specific effect in these regions which is unique. Hence, the WHO-INN a couple of years back proposed the name pirepemat which indicates that pirepemat belongs to a new CNS class, just like mesdopetam. So pirepemat combines antagonism if we go to the target perspective, combined antagonism at 5HT7 receptors and alpha-2 receptors. And we believe that this is a necessary combination to get to this very specific pharmacology relating to cortical strengthening. It's been well tolerated in clinical studies and those ranges has been defined for later-stage clinical trials. Looking at the regulatory aspects. We have an ongoing study right now which we have designed together with regulatory agencies, scientific advisers and regulatory experts. This is a totally new regulatory path. There is no other compound or product on the market which have paved the way. So we have to work together with the agencies to actually design the way forward to a potential registration of this product. So with the EU, we have received approval to run the study and all the ethical approvals. So the study is ongoing in EU. The FDA advised us to conduct additional DMPK studies and in vitro mechanism studies prior to an IND. And we have initiated and soon completed all those studies necessary. We expect to have those finalized during this quarter. The potential is, of course, very high with this program, looking at the cost -- the societal costs and the potential effect of the compound, combined makes that we have a quite interesting proposition for patients and for society and payers. This is also a program where we have conducted, of course, Phase I studies, single ascending and multiple ascending doses. We discovered that we had a sufficiently good PK property to move forward. We discovered also that it's tolerable. We have a safety profile which is acceptable for further development. We did a Phase I study in elderly comparing the new formulation of the compound, a tablet combination, to previous data on the capsule we used early on. Discovered that half-life in elderly is slightly longer. We have a higher exposure in elderly than in young people. Important information when it comes to designing the first strength of the tablets, but also the dosing for the forthcoming larger patient trials. We also found that we have a sufficient tolerability. We have a safety profile which is acceptable. We saw a few patients with elevated liver enzymes in the Phase I studies which occurred after treatment has been finalized. Then we've run a Phase IIa study which I alluded to before, where we saw quite -- where we see a quite -- I haven't alluded to that, sorry, which -- where we see a quite interesting profile in terms of efficacy. It appears to be safe and well tolerated in the intended patient population. And the -- we also saw here a number of individuals with liver enzyme elevations after cessation of treatment. That's after the treatment period. And the interpretation here is that we have a rebound effect with pirepemat following abrupt termination of the treatment, so likely dependent on excess sensitivity to norepinephrine in the peripheral systems. We have a Phase IIb study ongoing where we are looking at a number of endpoints. It's a double-blind placebo controlled trial with 165 patients. And we are recruiting in France, Germany, Poland, Spain and Sweden at present and we are looking at expanding into further countries and sites across the globe. A recap of some of the results from the Phase IIa data which are quite compelling to us. First of all, pirepemat not intended to treat symptoms of -- the core symptoms of Parkinson's disease, the tremor, rigidity and bradykinesia which Richard talked about. But the postural dysfunction. And we saw a clear effect on postural function. And this is -- these are symptoms which cannot be reached by any known treatment of Parkinson's disease including levodopa. So we saw an increase in -- improvement in balance. We saw a coupled to that, of course, a reduction in falls in patients who are defined as fallers in this trial. And these effects are thought to be derived from activation of cortical function. And in support of that, we also see a reduction in the apathy scores in the neuropsychiatric inventory that was used in the trial. We're looking at apathy. We also saw that in the UPDRS scale, I should mention. So we have both the motor function and the neuropsychiatric effects, combining our belief -- combined gives us a strong belief that we have this cortical effect in these patients. The ongoing study is to evaluate falls frequency as compared to placebo over 3 months. The secondary endpoints, of course, coupled to the falls in such a sense that we measure cognitive function, we also look at Parkinson's disease symptoms which is necessary in a trial like this, and of course, specific tests for postural dysfunction and then also classical CGI. So we can expect quite a lot of valuable information coming out from this trial. The trial is designed as a placebo-controlled trial. We have 2 different doses of pirepemat, 300 milligrams and 600 milligrams daily. We have a dose escalation introduced into this protocol differentiating it from the previous protocols and a dose de-escalation at the end of the trial and this is to mitigate some of the aspects of rebound effects that we've seen in the previous trials. There are also other aspects of inclusion, exclusion criteria, I should say, addressing the rebound effect in this trial. So moving rapidly into the preclinical and discovery or research projects, 942, where we are now looking at improving cognitive function and brain health in PD, but in -- also in neurology in a broader sense. And then 757 clinical candidate there too to treat apathy specifically. And then we have the P003 program. We are currently in lead optimization stage there and we are looking at a once-daily treatment for Parkinson's without the troublesome complications that we've talked about a little bit today. So 942, the status there is that we are moving towards Phase I studies in '23. We are currently in IND-enabling studies as it's called in the U.S. That means tox safety studies, regulatory and developing the CMC for Phase I next year. Similarly IRL757 is moving along towards Phase I next year. So these 2 programs are basically running parallel right now towards first-in-human studies. And the P003 program where we are looking at a once-daily treatment for Parkinson's disease. It's there to exchange the levodopa, that's our goal here. That's a long way there, but we'll start with moving towards a once-daily treatment which is the -- perhaps one of the most important aspects of PD, that is that levodopa has to be taken up to 6, 8 times a day, creates problems for the patients and therefore a once-daily treatment is necessary, we think. And we are nominating a CD this year. We are close to selecting our first compound in this program. And the objective here with the P003 program is to have a full efficacy, long-acting Parkinson's treatment. I will stop there and hand over to Viktor to go through the financial highlights of the quarter. Thank you very much.

Thank you, Nicholas. Some finances then. First of all, the geopolitical events and the global economies with the increased inflation and interest rates and so on, is affecting us as well. We are not immune. We do see some cost increases from our suppliers, not to a very high degree and nothing that is alarming, but we do see them. You could also see in our cost development, if you look at our P&L, it seems like we have a lot less cost this quarter than we had the last quarter. But in the middle graph on this slide, you can see that most of that has to do with the operations or the things that we have been doing for Ipsen as part of our handover of the mesdopetam program. Our own costs, so to speak, are still at about SEK 40 million per quarter and has been quite stable as you can see for the last 3 quarters. Going forward, we will increase our investments in the pre-clinical programs, the 757 and 942 programs and also the P003 program as well. However, we do have a strong cash position with almost SEK 300 million in the bank at the moment. To the right you can see that our employee or our headcount has plateaued the last 3 or 4 quarters at about 30 people. And we are hiring more people as we're currently, but mostly substitutions for people retiring. However, we look forward to recruiting and adding competencies to our company going forward as well. So a little more details on the figures. You can see that net sales are SEK 16 million, a bit more. SEK 13 million of those emanates from the upfront payment we received from Ipsen. It was about SEK 240 million and we took roughly SEK 25 million of those, set those aside to cover the cost for completing the Phase IIb study with mesdopetam and we are matching those SEK 55 million with the cost we have going forward. So this quarter we have taken back you can say, SEK 13 million of this SEK 55 million. And when the quarter ended, it was about SEK 9 million left in that reserve, which likely will be used during Q4. And after that if there are any more costs relating to the Phase IIb program, we will take that over the P&L as normally. The other SEK 3 million are other services that we have performed for Ipsen relating to the handover and -- of the program. You could also see in this table that we have increased the number of shares a little bit during the quarter and that has to do, as Richard said in the beginning of this presentation, it has to do with the acquisition of know-how relating to the P003 program that we announced this spring. So going to our analysts, we are still covered by Redeye, ABG and Edison and I think that they will -- or I know that they will have some questions to us in the end of this presentation. And with that I hand over back to Richard.

Thank you, Nicholas. Thank you, Viktor. Very nice presentations. I'll just carry on to close out the presentation now. It's been a busy quarter with other objectives, primarily to increase our visibility and company outreach, very busy with media coverage and presentations and you can see a summary here of where we've been in the last few months and the next quarter, and indeed the early part of next year looks very, very busy as well. So you're going to see an increasing presence of IRLAB at scientific, clinical and indeed shareholder and investor meetings and presentations. So just to recap, we have a very rich pipeline, including a portfolio of new agents to treat patients with Parkinson's disease. Mesdopetam coming to the end of Phase IIb has been licensed to Ipsen to address levodopa-induced dyskinesia. Our unencumbered assets pirepemat, 942, 757 and our research program, 003 continue very, very well in their development program with pirepemat leading the way in a Phase IIb study and looking forward to taking 942 and 757 into the clinic next year. We have a lot going on in our R&D function and therefore, we anticipate a very strong news flow in the coming year, 1.5 year, 2 years. So we have a table here of where we can anticipate some milestones in the fourth quarter of this year, first half of next year and indeed second half of next year. And indeed, multiple events that we've already committed to where you'll have visibility of IRLAB and receive business updates. So in summary, the outlook. Well, as I've said before and on joining IRLAB I can confirm, we have a very, very solid foundation for a biotech company. Our programs are developing mostly in the clinic and our research engine is very productive. Our business development has really confirmed that the work that we're doing, the assets that we're creating are truly robust and a great commercial potential illustrated with the Ipsen transaction. Building for the future, we can look forward to the data from mesdopetam and anticipate that Ipsen may well take that into Phase III and further development. We, of course, will continue with Pirepemat and the development of assets. And we remain in complete strategic control of these unencumbered assets to either develop them ourselves or indeed to partner for them. And we can even start thinking now about potential commercialization and I understand that Ipsen is quite excited about the potential for the commercialization of mesdopetam. So to summarize, IRLAB, pioneering biology, particularly in Parkinson's disease based on ISP technology. Focused strategy, developing assets for treating patients along their journey with partners disease. Robust validation, we have 4 shots on gold, each one with the potential to be in a blockbuster and a very, very robust organization and strong balance sheet to deliver on our R&D promises. And maybe with that, I should stop, and we can open for some questions.

Thank you so much, Richard. This is the first quarter that you were reporting where you have been operational as CEO as a IRLAB.

Yes.

What was that like?

Well, it's great to be here. It's a real privilege to have so much activity and so much good news to report and it's really excited to look forward to the next few months and indeed for next year.

Like you said, your balance sheet is in good shape. But when can we except sales to be more stable on a higher levels?

Well, I mean, as I was -- as a biotech company, we issue a few, but hopefully very large value invoices. So we can anticipate that there could well be some milestone payments due in the future. We're not in full control of that. But the most important thing is to develop the value within our assets rather than looking to realize that straight away.

Yes. And on the cost side you have multiple studies -- clinical studies going on over time. So are they more stable at the same level around SEK 400 million?

Yes, I understand. I think as Viktor alluded to, our R&D pipeline is rich, it is expensive. We're in a very good position at the moment. We have high value inflection points on the horizon. So I think we're in good shape. But certainly cost will increase as clinical activity increases.

What's your focus on this ongoing fourth quarter?

Yes. My focus, of course, is maintaining and growing our visibility. So we've got excellent programs with great potential and we need to sell them with a very large audience. So both in the industry context, in the clinical scientific context as well as in the shareholder and investor community. So I'm out and about very, very busy sharing the news flow, the activities, the updates and the anticipated milestones. I think that's really my priority as well as helping Nicholas, Viktor and the Board with strategic direction.

Okay. And with that I would like to hand over to analysts covering IRLAB. And first out is Soo Romanoff, Managing Director of Healthcare at Edison.

Mesdopetam wrapping up, could you provide guidance on what a good top line result would look like and what are the key things to look for since this is such a complex area?

I can take a first attempt and maybe Nicholas can add into that. We think that a clinical relevant result would be an increase in good ON by 1 hour. And of course, we anticipate and hope for much more than that. And again, I reiterate that the good ON that we're targeting is at the expense of the bad ON which sets us in quite a different league. So not only the patients experienced more quality time during the day, but they're actually experiencing less poor quality time during the day. So 1 hour will be a good result. We're hoping that we could achieve a lot more than that, but that would be a clinically significant outcome.

I think there's a lot of movement here with the closing of mesdopetam and all the pre-clinical activity. Can you give us an idea of the anticipated expenses? I think this is an extrapolation of the first question and what Viktor kind of went through. And maybe anticipated patient counts for the new trials.

Well, we haven't actually offered any guidance on that. But I think to recap what your question was asking is, what would be the dynamics of the Phase I studies in 757, 942. Well, one of the purposes of giving quite a comprehensive clinical update this morning is to show that the well-trodden path that IRLAB is now taken in developing our first-in-class assets. Remember, these are first in class. No one has ever done this before. We need to work closely with the regulators and ensuring safety and tolerability is the first objective and then looking for clinical signals. So whilst we haven't yet defined or indeed communicated the scale and scope of our Phase I studies, we should anticipate that there being a similar pattern. So single ascending dose studies and then multiple ascending dose studies in healthy volunteers and then toggling into patient populations. So relatively small and relatively low cost Phase I studies are on the slate for next year.