Hi, and welcome back. My name is Gonzalo Artiach, Pharma Biotech Equity Analyst here at ABG. The next company presenting today is IRLAB. With us, we have the pleasure of having here today the CEO of the company, Gunnar Olsson. Gunnar, the stage is yours. Thank you, and good afternoon. It's a pleasure for me to give you an update from IRLAB. So what is IRLAB? Well, IRLAB is a Swedish biotech, and we have a focus on developing better medicines for patients in Parkinson's, as a way of hopefully transforming the lives of the patients. Why are we doing this? Well, there are some 11 million people with Parkinson's today, and it's a very rapid increase, so we anticipate it doubling in the next 15 to 20 years. Parkinson's is a serious and lifelong progressive disease, and many of the symptoms and complications during the disease journey, there are no or very limited treatments available. So it's a very large unmet medical need, and with a large unmet medical need, of course, then there is a great commercial potential. How do we do this? Well, we're building on cutting-edge understanding of the disease. The reason being that our key scientists are the same scientists that were around Professor Arvid Carlsson, who received the Nobel Prize for all his studies in Parkinson's. We have developed a unique discovery platform to identify new CDs. These platforms gives very high degree of novelty, gives us a good way of getting good IP position, and it has a higher probability of success compared to industry standard. That, of course, will reduce the cost for us. So with this platform, we have generated this portfolio of five compounds spanning from the preclinical to phase III readiness. Lead compound being mesdopetam, where we are now preparing for an end-of-phase II meeting with the FDA to define the phase III program for treatment of levodopa dyskinesias. This compound can also be used in psychosis, although the leads, the levodopa-induced dyskinesias, is really where we have focus today. Our second compound, pirepemat, also a novel treatment. We're here aiming to reduce the risk of falls. For individuals with Parkinson's, falls is the most bothersome symptom that they describe, and today there is no available therapy. Here we are running a phase II-B study in Europe, where we anticipate top-line results end of first half next year. This could also be used in dementia, but we have the falls indication now as the lead indication. And then we have the IRL757 to treat apathy, of course, in Parkinson's, but also broader in other neurodegenerative diseases like Alzheimer's. Cognitive impairment, that is the IRL942 compound, again, Parkinson's, as well as broader in the neurodegenerative area, where, of course, Alzheimer's is there. This compound will be phase I-ready first half next year. And last, IRL1117, a new treatment for the cardinal symptoms of Parkinson's, the tremor, the bradykinesia, and the rigidity. And we believe that with this profile, something that is at least as good as levodopa, but without the complications we see during chronic levodopa, this has the potential to completely replace levodopa in the long run. Talking about Parkinson's, you see at the middle of this cartoon, time point 0, and that's where the diagnosis of Parkinson's is made. After that, you see the steady progression of new symptoms, motor symptoms, as well as psychiatric symptoms. It is clear that not just one treatment will take away all these symptoms. You need to focus on different things with different molecules. What about the IRLAB portfolio? If we start with mesdopetam, you see here the shaded gray areas. That's where we will see mesdopetam play. For pirepemat, we have these areas where we will play, and for IRL757, IRL942, IRL1117. Altogether, you see that we will be able to treat the great majority of symptoms and complication in the Parkinson's patient. Of course, through different combination of therapies. Some words about our compounds. Mesdopetam, our lead, it is a completely new way of treating levodopa-induced dyskinesia by blocking the D3 receptors in the brain. And as I mentioned, it also has a potential in psychosis in Parkinson's. We have very good animal data describing that.... We have just finalized our dose-finding phase II-B study, and here are the top-line results. You see two, two different boxes here. The left one, that is analysis according to intention to treat, the FAS population, full analysis set. And to the right, you see the per protocol analysis, where we have analyzed according to the dose that the patient actually took, and that they took at least 80% of prescribed medication. What you see here is a very clear dose-dependent efficacy with regard to antidyskinetic effect. You see that by the effect on good ON-time, as well as the effect on UDysRS. But in addition to this, we also see a dose-dependent effect on the good, sorry, on the OFF-time, and that is actually an antiparkinsonian effect. So we have here a very unique combination of effects: antidyskinetic effect, antiparkinsonian effect, combined with a safety and tolerability profile that is on par with placebo. We've never seen anything like this before in the Parkinson's space. In addition, of course, this study helped us to define the dose for phase III, 7.5 milligrams twice daily. Of course, when you have data like this, you wonder, can we get this approved to get to the market? And we've looked into the approval of the only product that is available in the United States to treat LIDs, levodopa-induced dyskinesia, amantadine ER. And you see in this table that we have listed the endpoints that we understand is the endpoints that the FDA will go for when you submit the new file. When we look then on the numbers to the left, that is the intention to treat population, you see that we actually hit primary endpoint as well as all the three safety endpoints. Meaning that if we can repeat this in our next pivotal trial, then we have a product. To the right, you see the per protocol analysis, and then we see that we actually tick all the different boxes with regard to the endpoints. So we are excited, and this is really what drives us to now approach the FDA in an end- of- phase II meeting, where we anticipate that it will happen early next year. Some words about PD-LIDs, this indication on the market. We know that roughly 25%-40% will develop LIDs of the population. However, less than 50% are today treated for their LIDs, and that is because the only available therapy has such a bad safety and tolerability profile. So there is a large undertreatment. So there is a large additional population that a new, well-tolerated, and effective drug could gain. And then just to talk about the differentiation opposite this amantadine that is available. In this table, you see the two right-hand columns, that is a copy from the label text for amantadine ER in the United States. And then you see left on that, that is our phase II-B data. And if you start by looking at the two placebo groups, you can see that the placebo groups are very similar. Then we go to the mesdopetam group, and you see that mesdopetam and placebo is almost exactly the same. Whereas when we look at the amantadine, you see very serious psychiatric side effects at very high, high frequencies, psychosis in more than 20%. So it is a very high degree of differentiation here. So this is why we in the company are so excited about this as a great opportunity. We have a well-differentiated drug based on dyskinetic effect, antiparkinsonian effect, super safety, and tolerability profile. We have identified the dose for phase III, and we have a very strong IP position with patent protection into the early 2040s. And then on top of this, many potential life cycle indications to expand the market, both within LIDs, so going from treatment of LIDs to prevention of LIDs. We have good animal data supporting that, and that would mean that you would have the combination treatment of levodopa and mesdopetam. On top of that, the psychosis in Parkinson's, as I mentioned, as well as tardive dyskinesia, the type of dyskinesia you see during chronic neuroleptic therapy. Leaving mesdopetam, and then looking at our second compound in clinical testing. That is pirepemat, where we are aiming to reduce the risk of falls in Parkinson's patients. It's a completely new mechanism, this as well. We have now an ongoing phase II-B study running in Europe. Among patients with Parkinson's, almost one in two falls recurrently. When you fall, you may get an injury, and if you get an injury, it's a very expensive thing. It's estimated in the United States that it takes some $30,000 per fall injury. Very importantly, today, there is no treatment available for this type of therapy. Our status, that is, we are now running the phase II-B study since last year. All our centers are up and running, and we anticipate to be able to have the top-line results end of first half next year. And as you see, we count on an addressable patient population in the order of 2.5 million patients. Just very quickly, the data that we generated in our phase II-A study. You see to the left that we have no effect on the cardinal symptoms, but we have a profound effect on what, what we call the postural dysfunction, and that is that you, you have problem with balance. And in the mid and right, you see that we have a substantial effect on reducing the, the problem with balance, and that translate into halving of the risk of falling in this study. On top of that, we have a very significant effect on reducing apathy, and very, very interesting, you see that that translates over to caregiver distress. So not just the patient feels better, also the environment around the patient notice that there is an improvement. We have also the three preclinical projects. The IRL757, that is the one to go for apathy, addressable population in the range of 2 million-7 million, and we are now working in late preclinical development so that we anticipate this to be phase-ready before year-end this year. The IRL942 for treatment of cognitive dysfunction, addressable population in the order of 6 million, and we anticipate to have this phase I ready, first half next year. IRL1117, our, what we say, next generation Parkinson's treatment, where we believe we have the, the, the potential to replace levodopa. We anticipate that this will be phase-ready by end of next year. So if we then look at the company, what is the key priorities for us to really create value? Of course, in the clinical setting, it is to get the end- of- phase II meeting, and it is to complete the study with pirepemat, so that we get the top-line results. For the preclinical projects, we need to make sure that they are ready to go into clinical testing. On the finances side, in order to drive all our projects, of course, we are having a very intensive period with lots of business development activities across the portfolio, but with a focus on mesdopetam and the IRL757 and IRL942. In parallel, we continue with all the discussions with different players in the capital markets. When we look to the next 18-month period, we have multiple possibilities for high-value creation. Mesdopetam, as I said, it is the end- of-p hase II meeting with the FDA to define phase III. It is business development to finance the phase III activity. Pirepemat, it is the readout with top-line results of phase II-B, and following that, initiate business development activities in order to finance phase III. With the preclinical project IRL757, IRL942, of course, get them to be phase I-ready and continue development collaboration discussions that are presently ongoing. For IRL1117, it is to start to get it phase I-ready, so that we can start it for phase I. It is a very exciting period for us at IRLAB over the next 18 months, and I hope you agree. So IRLAB, pioneering biology, we have the ISP platform to generate highly novel, candidate drugs with a high probability of success. Focused strategy based on the expert, areas that we have been working with for very many years. We have validated our business model. We have identified new candidate drugs, taken them up to clinical proof of concept, and made deals. We have a broad, and I would say, world-leading portfolio in Parkinson's at the moment, and it is an organization that is positioned for success. So with that, thank you, and over to Q&As. ... Gunnar, thank you very much for such a nice presentation, and now we have some time for questions. I would like to start asking you about your mesdopetam program. You are preparing now the end- of- phase II meeting with the FDA, but I was wondering if you could give us some words on a potential phase III program in terms of how many patients are you or would you need to treat in order to move forward, and in terms of endpoints also? Yep, it's a very good question. Here, I want to start by saying that this is very different from Alzheimer's. And why do I say this? Well, if we talk about sample size of a trial, if we were to get a label with only this kinetic effect, we're talking about a phase III study of 150 patients. Now, we believe that it's strategically better to get a label with antidyskinetic effect and antiparkinsonian effect, then we need to increase so that we end up on 200 patients. So a two-arm study, 100 patients in each, and compare that to Alzheimer's, that we know that you need in the order of 2,000-3,000 patients. Also, the study duration is very different. In this indication, we anticipate a double-blind period of three months, and for the Alzheimer's situation, then we are talking about roughly three years. Interesting. And in Europe, for a potential filing also in Europe, would it be the same requirements that the FDA ask for? We anticipate that, but it is a different situation in the United States and Europe from a regular point of view, because it's only the FDA that has had an approval for a product with that label. And that is actually the reason why we have selected to go to the FDA first. So that we have the discussion with the authority that has the precedence, and then, of course, we will also move into the European Regulatory Authority. I don't foresee that there will be a different position in the European, but as I said, we have made the decision to go first the FDA and then secondly, into the EMA. Thank you. A question on the pirepemat program. Yep, yeah ... in the pirepemat program. What, when you have discussions with key opinion leaders and specialists, apart from demonstrating the statistical difference between the arms, what are the magnitude of effect that clinicians would be happy to see in your trial to be happy with the data? I think that because this is such a big problem, any type of reduction would be beneficial. Now, based on the phase II-A data, it's a small study, but we had a halving of the risk of falling. That is seen as a dramatic, dramatical step forward. Yeah. Okay. And one of the effects that you just presented from pirepemat is also a decrease, potential decrease in apathy. Could you give us some, some color on why are you pursuing a new asset now in preclinical stage IRL757, instead of going for with pirepemat, where you already have seen some, some apathy? When we have seen pirepemat, and we've seen different type of effects coming out of that, we have actually then tried to develop improvements in two different molecules. One, the IRL757, we have had the aim to really drive the effect on apathy as far as we've come. And then the other aspect, that is that we also actually see some effect on pirepemat, on different signs of dementia. And then we have said, "Can we find a molecule that has an even more profound effect on dementia?" And that became the IRL942 molecule. So we believe that pirepemat will have its main place in prevention of falls. And then IRL757 will be the one to really treat apathy, not just in Parkinson's, but broader. And the same with IRL942. It will be our compound for dementia, not just Parkinson's, but much broader. Mm-hmm. Great. And a more broad question, regarding PD-LIDs and PD-Falls. I mean, from what you describe, and it is a real problem, in Parkinson's patients. But one of the things that on the space is that there is not much competition, there is not much... There are not many players in that space trying to develop new therapies for this. Could you give us some words on why is it the case, and is it because it's very hard to treat, it's not very well understood biologically? I mean, a little bit on that. Of course, there could be very many different explanations, but if you ask me and what I believe and what I make as a judgment, then I think it, it's a very difficult area. It's difficult because so many have tried, and this has led industry to have a lot of focus on different ways of administering levodopa. So pumps, different formulations, different combinations. What we have had as an advantage, that is this very deep knowledge and understanding of the disease through the Arvid Carlsson Research Group coming into the company or actually starting the company. And that, together with a very, very special platform for identifying new CDs. We are not doing the target-based screening as one example, a very important example. We are doing phenotypic screening by use of systems biology, and that means that the type of molecules that we find would never be found in companies utilizing the target-based screening. So this gives us an advantage. It also gives us, as I mentioned before, tremendous novelty, which means a very strong IP position. And this is why we have, for all the compounds today, IP protection well into the 2040s. And especially with mesdopetam, that you are on the threshold to go into phase III, and you still have a patent protection that is just below 20 years. It's a very unique and special situation, but it's very good because with all the life cycle management possibilities, you actually have time to do those additional indications to really explore the market as long as you have your patent protection. Very interesting. Gunnar, I think we have to leave it here and because of time reasons, but thank you very much for being with us today here and for your nice presentation. Thank you for inviting me.