IRLAB Therapeutics AB (publ)

We will get a presentation by the company followed by a Q&A with equity analysts and viewers can ask their questions in the live chat. To present today we have iLab CEO Gunnar Olsson, Executive Vice President R&D Niklas Waters and CFO Viktor Sivic. Hello, it's great to see you again.

Thank you. Thank you, and good morning, and welcome to the IRLAB quarterly update. Could we add the slides? Next slide, please. Next. The agenda for today, that is that I will give you an update of the news in the period, and this will be followed by Nicholas Waters, who will give an R&D update. Victor Sives will then give an update on the financials, and I will come back with some concluding words before we enter the Q&A session. Last year, the fourth quarter was a great quarter, but even so, I think that the start of this year has been exceptionally positive. Next slide. We've had some very great key achievements, and I have the key highlights on this slide. Yesterday, we signed the collaboration with MSRD and Utsuka, which funds the 7,500 projects through clinical proof of concept. And that means that now we have this particular project fully financed through proof of concept. Earlier this year, we had a successful end-of-phase 2 meeting with the FDA for mesdopetan, and that means that we now have the phase 3 study program confirmed. We've had and generated new insights from the phase 2b study with PIRCMAT, and that has led to regulatory approvals to reduce sompesize with retained statistical power to detect treatment effect. And the fourth, we just had the regulatory approval to start phase one with 757. And we anticipate that the study will start during this month. Next, please. So going from these high-level highlights to some more details. Starting with 757, that is now fully financed through proof of concept. We will run the initial phase one study based on the grant that we received from the Michael J. Fox Foundation. And then the MSRD agreement will fund all the rest up to and including a clinical proof of concept. For the initial phase one study, we have the zero contracted. And we have now the regulatory approval and we anticipate that this study will start before end of the month. Next please. So the development collaboration with MSR D Otsuka. What is it about? Well, the scope that is really to take 757 through clinical proof of concept and this in two populations. It is both in Parkinson's and Alzheimer's disease, two populations where apathy is very frequent and a very large unmet medical need. And we have now secured the financing to do all this next. So what will the different parties do? On EarLab, we will receive upfront payment and activity-based milestone payments We will execute the development activities. We will also retain the full ownership of the product and all the IP. And on the MSRD side, they will, in addition to paying the upfront and milestone payments, they will fund all the development activities under the terms of the contract. MSRD may extend the collaboration beyond proof of concept, but that is subject to new negotiations and new deals. And in the event that MSRD would not extend the collaboration, well, then they will receive low single-digit royalty on future sales. Next. So what does this mean for IRLAB? It is very important, and there are very multiple positive aspects of this. The first one is, of course, that this brings near-term cash flow to us. Up from the milestones, eight and a half million US dollars, three million US dollars upfront, and the rest in activity-based milestones. It secures the full financing of the development activities, as I said, in two populations. with apathy, Parkinson's and Alzheimer's disease. And this also gives us the opportunity that when we have generated this data, I would really stress this clinical data, that's when we can then go out and seek licensing for commercialization of the product. And of course it could be Otsuka, or I should say MSRD Otsuka, but it could also be another party. But the value of the project is of course much larger when we've generated the clinical data. This also provides additional external validation of the R&D innovativity as well as the quality. It is also a validation of our partnering and business development activities. With this signed deal, our assessment is that this deal provides conditions to run the bus business without additional capital injection past a potential licensing deal with Ms. Dobton and past the top-line data in the Phase 2b study with PIRTMAT. We have not communicated the total value of this steel, but just to give you a benchmark, the industry average, you estimate the cost to take a compound from phase one initiation up to proof of concept to be in the range of about 25 million US dollars. Next, please. If we then continue with mesclopetal, we're continuing driving this forward. In our lead indication, levodopa induced dyskinesia, we had a successful end of phase two meeting with the FDA. So we have now an alignment on phase three program. And also importantly, we have an alignment on the path forward to NDA filing for market approval. Parallel to all these regulatory activities, we have continued with very high intensity of business development activities. In the second indication for Mesopotam, the psychosis in Parkinson's disease, we have made progress. We had a scientific article in neurotherapeutics reporting the antipsychotic effect of mestopetone in a preclinical model and this of course further validation of mestopetone as a product. I should though state that of course our key focus now that is to drive the initial indication levodopa induced dyskinesia but it's very good to know that there are also other opportunities when you have taken the first indication all the way through. Next, please. Here at MADD, I call this a regulatory update because it has had some regulatory implications. As you know, we are running the REACT-PD, our dose finding study, phase 2b study, in patients with Parkinson's and frequent fall. And the aim is to reduce the risk of fall. We have done blinded analysis of the data, and that shows that we, following initiation of all recruiting centers, we have a very stabilized patient recruitment rate. We have also observed high and stable fall rates at baseline, actually more than what we anticipated. And this has implications. Next, please. The implications is that we have a high probability to detect treatment effects even with a lower sample size. And we have now reassessed the sample size, and that has been approved by the regulatory authorities so that we can run the study with a lower sample size. Secondly, by using now the data-driven estimates, we can get much more accurate study timelines. And based on that, we see that we anticipate completion of patient recruitment during the third quarter this year. Next. We have also our two preclinical projects. And here we continue with CMC work to develop the API and the we are, as you see here, estimating these projects to be ready for phase one, end of the year or early next year, because we need to find time slots for toxicology studies in the CROs. Next, please. During this period, we've also had participation and we've given presentations at scientific meetings and financial conferences. We attended the ADPD meeting in Lisbon, where we presented two posters, one describing the REACT-PD, the PUREPMAT study in detail, And the second poster that was to give the preclinical in vivo characterization of 1117. And this is the first time that we have revealed data on this compound. We also participated in the BIAS Lund meeting where we presented different statistical methodologies to improve study designs. and also how to use statistical methods to monitor studies as they are ongoing. At financial conferences, we presented here in Gothenburg at the Life Science Day. We took part in a fireside chat with ABG, and we participated in Red Eye Investor Forum. So all in all, a period with Lots of very important progress, which we are, of course, very pleased to see. Now I think it's time to leave over to Nicolas to take us through an R&D update. Please, Nicolas.

Thank you, Gunnar. I will try to follow on that smashing news flow that you actually give. Can we have the next slide, please? And I will just continue with stressing some of the very important and quite substantial developments that we've had during the first quarter this year. I'm going to talk about this, but I would like to continue discussing the clear path to NDA that we have chiseled out together with the FDA. And that's a really important milestone. Further regulatory validation has been provided also. Through the approvals of the refinement of the study protocol for PIR-PMAT, Gunnar discussed a little bit around the aspects of why we did this. But the important thing here is that we have been given the nod from all of the regulatory bodies around Europe that actually has seen the strategy that we want to put forward. That means that we can now reduce the size of the study with about 25% with retained statistical power. And that's really, really important. And also, as Gunnar mentioned, we have learned a lot about these patients and their condition of life during the progression of the study. And then Last but by no means least in this list of regulatory successes, we have now gotten approval for our third programme to enter into clinical trials. And I think this causes a little pause here, because three clinical programmes in a small company in Sweden is quite unique. And remember that these are drugs that where we have developed the hypothesis, we have developed or discovered the molecules themselves. We have created the description, the pharmacological description of the program. So we've taken them through IND enabling studies and got into phase one or approvals for phase one for all of these. And of course, we are in phase three, we messed up with on phase two B with group mod. So at this stage, with EarLab, we have zero attrition. And that's quite remarkable. Next slide, please. And so we go on. This is a slide we've shown a number of times where we look at the symptomatology of Parkinson's, where we have looked at different parts of the symptomatology and found openings for novel treatments. Next slide. Mestopatome covering dyskinesia, but potentially also psychosis, where we are building a case. Next. We're looking at the falls, the balance problems, but even swallowing as a potential improvement here. Next, please. And now also IRL 757 addressing the very important aspect or a very complicating aspect of neurological disorder, and that's apathy. And there are no treatments out there for apathy today. Covering that as well. Next, please. Now, the next challenge for us is now to bring 942. And next slide, please. Next, click there. And 1117 also into clinical trials. And we are moving along those paths. Next, please. A few words on mesto-hepatome next. This is a first-in-class molecule with a novel mechanism. From a patient, a treating physician, and from a marketing potential, novel mechanisms are really important. This is a drug which inhibits dopamine D3 receptors, and that leads to a reduction of the involuntary movements induced by levodopa. We have a very strong patent portfolio around this asset, stretching, potentially stretching exclusivity based on patent into the 40s. Next, please. Going back to the same topic again, but I think that it's important to stress this, that we have confirmed alignment between the agency, the FDA, and EarLab on how the Phase 3 program is going to be designed. And this goes both to the efficacy trials, but also to the study that is determining the safety of the study, where we have a one-year safety follow-up for the patients entering into this trial. And also a number of additional aspects relating to CMC, etc. We are in alignment with all these aspects of the program. So the roadmap to NDA is clear to us. In the wake of the discussions with the FDA, we have also now initiated a process to get into discussions with European regulatory agencies before we press the button, the start button for the phase three, to see if they have any additional requirements that they want to see for a drug treating dyskinesia. And we should all remember that there is no approved drug for dyskinesia in Europe yet. So in Europe, this program is the most advanced that we know of. And then we have the possibility actually to start the trial program later on this year or at the very end of the year. That's a clear possibility. Next, please. I wanted to show you this. This is, of course, very deep scientific data, but it illustrates the potential for masto-hepatomas and antipsychotic. If one just looks at the graphs there that are introduced into the slide, at the very, well, from my perspective, left side, you see a red band of aberrant signaling captured from the brain. This is electrophysiological captures. And then there is a treatment, the next panel represents a treatment which has been used as an antipsychotic in PD, that's clozapine, which reduces that aberration. And then you see the effect of two doses of mestopotam following that, which basically takes away the aberrant signaling, but also restores what is so necessary, and that is complexity in the signaling between brain regions. And this is a very good example of a very advanced way of studying psychosis in the model of Parkinson's, where mestavputan excels in terms of efficacy. Next, please. And this was published recently, I should say. Piripamat, next, please. Going back to the false indication again, And this is one of the biggest problems in Parkinson's disease, the falling. It's introduced at the mid to late stages in most patients. About half of all patients fall recurrently. The quality of life limiting aspects of falling is not fully appreciated. There's lots of literature describing the complications, but also the cost of the falls. And for a fall that enters into a hospital in the US, the cost estimate is around $30,000. And that was a couple of years back. So it's probably much higher today. If one can reduce the risk of falling just a tiny bit, 25 to 50 percent, then that would be a very significant improvement. We have an ongoing study, as most of you know, across Europe. We expect to finalize recruitment in this trial during Q3. That's our prediction right now. And that's based on our discussions with the regulatory authorities, which we've been into before this presentation. Next, please. Piripimat, just like Mr. Opeton, represents a totally novel class of CNS-active compounds. And this is not us saying that, that's the WHO INN saying that. And that's also a very important aspect of the commercialization of a product. To have a new class is, of course, a huge advantage. This is a drug which acts through inhibition of at least two targets in the brain, alpha-2 receptors and 5H7 receptors. And also here, we have built a very strong patent portfolio or estate around it, stretching exclusivity potentially into the 40s as well. Next, please. Updates in Q1, and Gunnar discussed this a little bit, but we have looked at blinded baseline data to understand better how these patients behave. We have higher fall rates. We see stable baseline. That's interesting that the patients tend to fall on a steady pace during at least one month, the run-in period on our study. And we saw that withdrawal rates were slightly lower than we anticipated, which all these things together means that we can actually reduce the sample size. So we've discussed that with the authorities. We also discussed how to handle this type of data statistically. It's not trivial, I should mention. It's not trivial at all. And they have accepted our way of looking at the data. And that's really, really important. Next. 757, we talked a lot about that today. So we go to next slide. Apathy as such is a huge problem in neurological disorders you can see a panel here with different frequencies but about 20 to 70 percent of all patients with parkinson or alzheimer actually experienced apathy and this is a condition that not only affects the patient but also the surroundings the surrounding in terms of the the caregivers There are some hypotheses around the origins of this, and we have focused on one of them, and that is the connectivity between cortical areas and lower brain areas. 757 has a unique profile in this respect, restoring connectivity between cortical and subcortical regions, which could be a way to treat apathy. Next. So the main progress in this period has been, of course, the completion of the preclinical package, the IND enabling studies. We have received the funding from Michael J. Fox Foundation. We are now initiating the phase one program together with the CRO in Uppsala, our colleagues at CTC. And we are now also, since yesterday, in a collaboration with the MSRD Yotsuka, which actually is really, really important. This supports the program all the way through proof of concept, not only in Parkinson, which is our main goal, but also in Alzheimer's disease. So we'll get readouts from at least two indications through this collaboration. And the collaboration will be a true collaboration where we are working together with developing the product, we're developing the protocols for the studies together, and we will execute the studies. And we will be the sponsor for these studies, but of course, MSRD and ZUKA will have an important role in the program, just as MJFF has a very important role in the phase one SADMAD studies that we're conducting now. Next. The preclinical programs, since we now have moved 757 into clinical phase, we have two preclinical programs, 942 and 1117. Next, please. 942 is focused on cognitive dysfunction in neurological disorders. This is a huge market. There are still programs. unmet needs in this space. The current treatments, they work, but they could work better. And we think that 942 is that solution. 1117 is a totally new strategy to treat Parkinson's symptoms, the hallmark symptoms of Parkinson's. Also, a huge population around 6 million people around the world could be addressed. Next. So if one looks at some statistics on the occurrence of cognitive dysfunction, 12% in all people actually over 65 experience cognitive decline. And this is, of course, much, much higher in neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Today, there are a couple of possibilities to treat this condition, but we think there is room for better and novel treatments. working through different mechanisms or new mechanisms next please progress in this program has been ongoing we are developing the synthesis of the api necessary for the talk studies we are developing a drug product for coming phase one style studies right now and we expect to be able to start if we get the time slot at the CRO, one-month talk studies during this year, which means that we could be phase one ready at the end of the year or early next year. Next, please. Going over to 11.17, which is the last in the presentation, but by no means the least. This is a really, really interesting program, at least from our perspective, who have been involved in PD research for so many years, where we now have discovered a way to actually activate motor function over long periods of time without complications. So this also has the potential to be the first drug in a new class, which could actually compete with levodopa as a mainstay treatment for Parkinson's. Next, please. We are right now building a very comprehensive preclinical efficacy, tolerability and DMPK package before we go into doc studies. And what we've seen so far is that we have, after single doses, long exposure of drug, but also long effect of drug over 24 hours after one single dose, improving motor function. This without giving any of the complications that one see in parallel groups treated with levodopa. And in animals already treated with levodopa, if you switch to 11.17, the complications goes away and you still retain the motor function activation. So this is going to be a really, really comprehensive package. We are right now working on the development of the API, the synthesis of the product, and IPR, of course, filed a couple of years back and stretches into the 40s. with exclusivity next please and this is now victor's arena i will hand over to victor thank you nicholas uh finance report uh you can go to the next slide please