2023, IRLAB Capital Markets Day. On behalf of the company, I would like to extend our thanks to the local audience who have made our way here, and also to our online audience watching right now. My name is Mats Thorén, and on behalf of the company, I will be helping moderate today's proceedings. During the course of approximately two hours, we will hear from the company's management teams regarding the company's projects, the huge medical need for these projects, and what the market looks like. We also have the pleasure of having Professor Karl Kieburtz here. Professor Kieburtz is a professor from the University of Rochester School of Medicine, and he will be, together with the representatives from the company, talking about the treatment of dyskinesias. Looking forward to that.
At the end, we will have a panel discussion, which I'm looking forward to, and there will be a Q&A session. If we have time, I will take questions from our local audience, right here after each presentations, but most of the questions will probably come in a separate Q&A session at the very end of today's session. And in the Q&A session, our online audience, you will have the opportunity to put questions to any of the speakers today, and you should see a box just underneath the presentation on your screen, where you can send in those questions, and they will pop out right here. And, depending on whether we have already touched upon them or not, we will bring them up, to the extent we can in the final Q&A session.
So with that, let's get started, and I'll give the floor to the company's CEO. Please go ahead, Gunnar Olsson.
Thank you very much. Good afternoon, everyone. It is a great pleasure for me to give you an update on IRLAB and to introduce you to all the activities that we are involved in. So IRLAB, what is it? Well, it is a Swedish biotech company, and we are aiming to improve lives of patients and individuals with Parkinson's disease, and we're doing it by developing better novel therapies. And why are we doing this? Well, it's about 11 million people having Parkinson's disease, and it is rapidly increasing. In the next 15-20 years, we anticipate a doubling of the number of patients. Parkinson's is a serious and lifelong disease with many complications and difficult symptoms. And today, there is a lack of effective treatments for many of these complications and symptoms, and that means it's a huge unmet medical need.
With unmet medical need, there is, of course, a fantastic commercial potential as well. How are we doing this? Well, we are starting with cutting-edge expertise in the field, emanating from the research team around Professor Arvid Carlsson, the Nobel laureate that received the Nobel Prize for all his science in Parkinson's disease. We have created a discovery platform, the ISP. And this platform, building on phenotypic screening with systems biology and a lot of computer power, machine learning and things, we get a higher likelihood of success compared to in the industry standard. This, of course, reduce the costs of what we're doing.
Our strategy, that is that we are addressing all stages of Parkinson's disease and other CNS diseases when symptoms are the same as in some of the Parkinson's disease symptomatology and the type of complications. We are discovering all our novel CDs with our ISP, and that gives us true innovation. It gives us, as I mentioned, higher success rate compared to industry standard, and it gives us a very strong IP position. We're developing our candidate drugs from discovery up to proof of concept, and then we're seeking partnering to take the product all the way through. Here is our pipeline. Our lead molecule is the mesdopetam, with the lead indication, treatment of levodopa dyskinesia.
We have completed the Phase IIb study, and we are now moving towards an end of Phase II meeting with the FDA as a way of defining the Phase III program. In this area, dyskinesias, there are very few treatment options, meaning that there is a massive undertreatment, and that will, of course, in turn, result in a major commercial potential. Our second compound is pirepemat, that we now are running a Phase IIb study to evaluate the pirepemat effect on reducing the risk of falls, one of the absolutely key symptoms in Parkinson individuals. For this very complicated symptom, there is no treatment today, meaning that, again, here we have a very good commercial potential. 757, we are developing this compound for apathy. Apathy, of course, in Parkinson, but also in other neurodegenerative diseases where apathy is a common symptom.
IRL942, it is a compound that we are developing to improve cognitive dysfunction. Again, we will see that this has a place in Parkinson's, but also wider in other neurodegenerative diseases where dementia and cognitive dysfunction is symptoms. And last but not least, we have IRL1117. This is a completely new type of treatment for the hallmark symptoms of Parkinson's. And this has all the good things about levodopa, but it is devoid of all the negative consequences of long-term levodopa therapy. So a compound with this type of characteristics has the potential to really replace levodopa in the long run. So again, a molecule with a significant commercial potential. I will now talk a little bit about the disease and then try to see how does our products fit into the disease development.
This cartoon, you see the development of the disease or development of the Parkinson's. At the middle of the cartoon, you see the time point zero, and that is when the diagnosis is set based on the tremor, the bradykinesia, and the rigidity. After that point, you see the progressive nature with adding on psychiatric as well as motor symptoms, and you see a great number of different symptoms and complications that may occur. And I can tell you that there is no hope that one single treatment should take care of all these different symptoms. Instead, you need to think about what type of medication can relieve a certain type of symptoms. So with that, we can then see where do the IRLAB compounds sit. And if we start with mesdopetam, you see here the gray, gray shaded areas.
That is where mesdopetam will have its place. For pirepemat, it is these areas. For IRL757, yet another part, and for IRL942, and for IRL1117. And if we now take all this together, you see that with the portfolio that we have, we can actually treat the great majority of symptoms and complications that a patient may develop during the course of the disease. And that is, not through one single treatment, it is really by combining the different, therapies. And of course, this gives a very good possibility to individualize the therapy. But for us as a company, it is also important it gives a very huge commercial potential.
So with this, I think it's now time to invite our CMO, Chief Medical Officer, Joakim Tedroff, to take us through a little bit more, what is it that is important for the patient, and what does that give as a steer for us developing new drugs? So please, Joakim.
Thank you, Gunnar. Well, thank you, Gunnar, and thanks for having me. I'm going to talk briefly about what it is having Parkinson's, how it evolves, and what are the medical needs out there. And so just a few words on Parkinson's disease. It's a brain disease, the second most common neurodegenerative disorder after Alzheimer's disease. And its hallmark degenerative feature is the loss of dopamine and neurotransmitter that is important for our mobility, our movements. And it also controls emotions, thoughts, movements, and other things. Age is the most important factor for neurodegenerative disorders, just like Alzheimer's disease. There are environmental and genetic factors involved in the pathophysiology of Parkinson's, but for most patients, we don't really know what is causing their Parkinson's disease.
It is chronic and progressive, meaning that it gets worse over time, and it is lifelong. There's no cure and there's no way to stop it worsening over time. And patients are typically diagnosed early sixties and by the time after 10 years, they have a marked disability usually. And due to that, the population globally is getting older, the burden associated with Parkinson's disease is increasing considerably. You can see this was a few years ago, it was a publication talking about Parkinson's disease as a new pandemic. And in this article, the authors argue that Parkinson's disease is spreading like a pandemic. It is now also the fastest growing neurodegenerative disorder.
On the right panel, you can see people dying in PD in the US with Parkinson's disease has steadily increased per 100,000. In 1990, it was 3.2 people per 100,000. Now, in 2017, 8.4 people. So it has increased dramatically, and it's continuing to increase, showing that number of people with Parkinson's disease is increasing. So what's happening? Well, it's a very complex neurodegenerative disorder, not just affecting dopamine, but also other neurotransmitter systems like noradrenaline and acetylcholine. You can stage the various processes according to a so-called Braak staging, where the disease starts in the midbrain, where the dopamine cells are. Actually, already in stage three, you can diagnose the disorder, but it has been going on for quite a few years before you can diagnose this.
Then eventually, it also emerges into the cerebral cortex, causing balance problems and dementia. After 15 years, about 80% of patients have signs of dementia. This is what it looks like in a cartoon. Yeah, usually it starts with unilateral symptoms like bradykinesia, rigidity, and tremor, spreads to the other side. And at stage 3, this is an old staging called the Hoehn and Yahr. It was published in 1969 before L-DOPA was available. At stage 3, there is also postural dysfunction, that is balance problems, and stage 5 is confined to wheelchair. That's a journey that most patients go through in their Parkinson's disease.
You can see here at about 50% of patients globally have stage three or higher, that they have postural dysfunction, and 50% is below that. This is a publication just illustrating the quality of life of having Parkinson's disease. On the y-axis, it's the adjusted PDQ-39, which is a quality of life scale. The higher the number, the worse is the quality of life. And on the x-axis is the scale I just alluded to, the Hoehn and Yahr scale. And you can see that once postural instability occurs, then the quality of life gets very much worse, and it. So there's a significant shift in quality of life once this happens. And as you can see, also, as the patient progressing, the quality of life gets worse.
This is the symptoms that Gunnar alluded to. This is same cartoon. And with the spreading neurodegeneration affecting many other neuronal systems than just dopamine, you get different types of symptoms emerging, and many of them are not treatable today. And really, there hasn't been much of development in Parkinson's disease since I started as a physician, just a few new medications. And just a few words on what the patients with Parkinson's undergo. Well, they are diagnosed usually in their sixties, and then they receive therapy. Most patients receive therapy, and it's levodopa based. You can add other types of medications called dopamine agonists or enzyme inhibitors, such as MAO-B inhibitors. But most people, almost all patients, receive L-DOPA treatment, and that works very well. It's a fantastic drug.
It's safe, it's efficacious, but it works well only for a few years until the neurodegenerative process catches up, and patients develop dyskinesias, complications of therapy, hallucinations, wearing off, ON-OFF fluctuations, and eventually also symptoms that are not amenable by L-DOPA treatment. So L-DOPA has its limitations. It has a short half-life. It, it's only a small percentage that reaches the brain. It causes early wearing off. Its effect is very short, when the patient has come to a certain degree of disability, and patients develop motor fluctuations and dyskinesia, and that's very difficult to treat adequately. You have to fractionate the dose, you have to give pumps or do surgery like DBS, deep brain stimulation surgery. But it's a gold standard treatment. We've had it since the early 1970s.
It's effective, it's safe and tolerable, and it causes improvement in quality of life, at least short term... So when we ask the patients, the caregivers, the care professionals, "What do you want to see? What's the biggest problem in day-to-day life for patients with PD? What do you want to treat?" Well, priority one in one study is falls. Parkinson's disease is the number one falling disease. Patients with Parkinson's fall twice as often as otherwise healthy age-matched controls. Stress, treatment of stress and anxiety is also a priority. It's very patients get worse when they are stressed. They're usually very anxious. That may wax and wane with L-DOPA concentrations.
Priority number three was dyskinesia, because dyskinesia is involuntary movements caused by the treatment they desperately need, and once you have these dyskinesia, it's very little room to maneuver. If you increase the dose, which the patient generally needs, you get more violent dyskinesia. So you keep the patient on the lower dosing and more disability. So if there were treatment for dyskinesia, you could use L-DOPA more freely. And as I said, there's no treatment for falls. L-DOPA doesn't work for that. FDA has also done an initiative where they listen to the voice of the patient, gather patients, caregiver, other stakeholders, and in this survey, patients and caregivers asked for better symptoms for the core motor symptoms, treatment for impaired balance and coordination and cognitive impairment.
And impaired balance and coordination we regard as major challenge for the patient. So bear this in mind when we talk about pirepemat. So this was a short crash course on the burden of Parkinson's disease, and I will leave the word to the next speaker, which is Peter Wallich, who will talk about market opportunities in Parkinson's and CNS.
Thanks very much. I'm going to talk about the opportunities in Parkinson's and CNS, build off the last two presentations, and try to describe the fit for IRLAB in this area. It's a growing large market. We've talked about the 10.9 million prevalent cases. It's the second most common neurodegenerative disorder after Alzheimer's. Forecast to grow to 12.4 in 2027, and as we described earlier, the aging population is driving a need for treatment. It is set for a market expansion. Approvals of new pipeline drugs and improved diagnosis leads us towards a market expansion. Reimbursement issues, of course, in a market with a lot of generics is a barrier to uptake. New formulations and repurposing of levodopa usually move those products to second or third-line treatment.
But differentiated niche treatments can command high prices. So treatment of Parkinson's is heterogeneous. We saw the last two presentations that it's a highly personalized approach. It's complex. Several concomitant medications are used, especially in advanced cases. And whilst new treatments come out, often they bear the burden of additional adverse events or drug-to-drug interactions. And so in early Parkinson's, you can see on my, on your left-hand side, we try to avoid levodopa treatment if the motor functions are of low impact. But if they're impacting quality of life, the patient goes on to levodopa. As the disease progresses, we get the increased use of adjunctive treatment, and that's for to manage those new symptoms, motor or non-motor symptoms.
Eventually, the patient's gonna end up with more invasive treatment, deep brain stimulation, or Duodopa stomach pump. So it's a complicated area to treat. It's not a one-drug-fits-all type situation. But it is a dynamic and evolving market. Many brands, as mentioned by Joakim, levodopa, standard care, so that we have an increasing genericization in the market. Treatment of late-stage Parkinson's really offers a great opportunity due to the emergence of those motor and non-motor symptoms. Excitingly, there's a high level of pipeline activity in this area, but there is a slow progress. Transition to phase, from phase two to phase three, a lot of agents don't make it, and that underlines the complexity of research in these areas. Repurposed drugs and reformulations dominate the pipeline at the moment.
With the emergence of some late-stage readouts and NDA approvals in the next couple of years, we could really see a great impact to the, to the market. As Joakim mentioned, he's been working in Parkinson's for a long time, but there have not been a lot of new treatments coming out over that period. But of course, we must remember there's a need to balance the benefit and tolerability. We don't want to have new drugs with additional side effects causing problems. So today I'm gonna talk about the Parkinson's disease pipeline target areas for target areas, and I'm gonna look at from a perspective of the patient population we can address, and clinical utility, so effect, adverse events, and novelty.
And so what I've done is looked at disease-modifying and symptom treatment, but split it out a bit to make it easier. So on the very dark gray side, on my left, on the left-hand side of the screen, the new formulations, the levodopa formulations, they have a potential to treat a lot of patients, but they'll probably be treating less patients due to pricing pressures or second and third-line treatment. The subcutaneous infusions, levodopa or apomorphine, very interesting, exciting things coming out. Potential for patients in the later stages, and concerns at the moment with the adverse events are quite a reasonably high discontinuation in levodopa infusion trials due to skin issues. Deep brain stimulation, there's work looking at closed loop areas.
The orange circle, very exciting place, alternative to levodopa, optimizing levodopa. A lot of products in mainly the early stage there. Then we have the big curve, motor and non-motor symptoms. It's a big curve because depending on the treatment, the stage of treatment, the indication, it changes the patient's, patient size, target size. And then at the top, we have the two disease-modifying or slowing progression. So I've split them out, gut-brain mechanisms, looking at the microbiome, and then, the, the alpha-synuclein or gene or cell therapy areas. They're exciting areas. There's a couple of products in late Phase III stage at the moment, but you can equate those two areas as, equate it back to where Alzheimer's was 15, 20 years ago. So it's early-stage research.
Now, with IRLAB, we're focusing on differentiated medicines in niche segments with the greatest unmet needs. And so here you can see the two areas we're playing with. And so the products we have in development in dark green, the alternative to levodopa, and motor and non-motor symptoms, and in the light green, potential for IRLAB products to play in the disease-modifying, slowing progression side. And so here you can see our portfolio. It's a fantastic portfolio. We have mesdopetam for dyskinesia, pirepemat for falls, IRL757 for apathy, IRL942 for cognitive function, and mesdopetam for psychosis. Now, some of those, if we're looking at prevention, could play in the slowing progression area. And then on the alternative to levodopa, we have IRL1117 for antiparkinson's.
It's really fantastic and exciting to be able to talk in such a presentation and describe a portfolio where you have actually two products in mid to late stage. It's not very often you get that. Here we have mesdopetam, Phase III ready. It, dyskinesia, as Joakim mentioned, recognizes a key unmet need. We've, it's mesdopetam in the Phase II has been proven to have anti-dyskinetic effect and anti-parkinsonism. It has a good safety tolerability profile comparable to placebo. When we've talked before about new drugs with not wanting to have other adverse events, this is a great position to be in when we have a comparable to placebo compound. Low potential for drug interactions and contraindications.
Exciting. There's a low number of competitors in this space, and we have a strong potential to be the first in market with the indication ex US. And in essence, this could be the next new product for dyskinesia once it gets through it starts and finishes Phase III. And then the other exciting drug we have, pirepemat Phase IIb ongoing. Falls, as we've talked about, represents a major unmet need, high cost and high injury impact to patients and society. Again, a low number of competitors in the pipeline, so that's also very exciting. The studies so far demonstrate good tolerability and a good safety profile, and here we have the strong potential to be first in market with this indication. So it's very exciting stuff. So that's a very strong portfolio. What about the commercial opportunity?
So here I'm gonna talk about the number of patients that are available to us. And if we start with Parkinson's, you can see in the eight major markets, 7.2 million Parkinson's disease patients diagnosed, and then we apply the number of patients being treated, and so you have different percentages depending on the country, and so you come down to a level of 5.7 million. And then if we look at mesdopetam, pirepemat, IRL757, IRL942, and you look at the different prevalences of those disease, the of those diseases, you can then see we come down to numbers in of millions of patients who can benefit from these treatments.
You just have to do some multiplications with the current pricing of new novel drugs in this space to get a feel of the potential forecast for these products. And then when it comes to IRL1117, of course, this being a potential replacement for levodopa, could actually be a drug for all patients with Parkinson's. So it's an extremely exciting potential we're talking about. If we're looking at Alzheimer's disease, I'm looking here at the 10 major markets, in Parkinson's, I was looking at the 8 major markets. We have 11.2 million patients with Alzheimer's disease. Again, looking at the prevalences for apathy and improvement of cognitive dysfunction, you can get to the numbers of between 3 and 6 million patients, depending on the indication. So again, fantastic opportunities.
But not only that, we have further opportunities in the with lifecycle development and also pipeline in the pill opportunities. So for mesdopetam with the lead indication of dyskinesia, we can have prevention of dyskinesia and also psychosis in Parkinson's, and we can also have tardive dyskinesia as a pipeline in the pill opportunity. When we're looking at pirepemat with the lead indication of reducing the risk of falls, we can look at life cycle opportunities of prevention of balance disturbance and neuropsychiatric symptoms. And then if we look at 757 's potential initial treatment of apathy, we can be looking in the future at prevention of apathy - but also frontotemporal dementia. So each of these products have a great potential by themselves in their lead indications, but a fantastic opportunity with life cycle and pipeline pill opportunities.
So at IRLAB, we're, we're looking at offering differentiated new chemical entities. We're addressing high areas of unmet need. We have early to mid-late stage products in, in development. And to remind you, we have two fantastic products in mid to late-stage development. Our target is Parkinson's disease, CNS, and when these products go out to market, the expectation would be that they're targeting specialists in Parkinson's disease, Parkinson's disease and neurologists. The approach for partnering is to focus on these two areas: mid to large size pharma or specialty pharma, looking for markets with unmet needs. And our business development activities is, is definitely showing that the awareness of IRLAB and its development pipeline is increasing, which is a good thing.
We have continuous, ongoing, and frequent dialogue with potential partners, and we're looking at partnering, partnering opportunities across the entire portfolio. But the near-term focus is, of course, mesdopetam, which is Phase III, Phase III ready, and 757 and 942. So thank you very much, and I'm handing over to Nicholas.
Thank you, Peter. Exciting information you share with us on the potential of the drugs that we're developing. I will talk a few words about the results from the complete study with mesdopetam in Parkinson patients suffering from LIDs. I will share this section of the presentation with Professor Karl Kieburtz as well, who will focus a lot on the strategies towards the regulators and with a special focus on the FDA today. So what is mesdopetam? This is a first-in-class compound with a novel mechanism. We've been talking about that for a couple of years.
This is a drug which primarily inhibits a receptor called dopamine D3 receptor, and this is a receptor that behaves ill in the Parkinson's situation, where it actually turns up in places where it shouldn't be and is coupled and/or associated with the development of dyskinesia. So we have developed a D3 antagonist to treat dyskinesia. Then a very important aspect of the co- which ties in with the commercial strategies here is the patent portfolio or the patent estate that we have developed around mesdopetam. And today, we expect that we can defend exclusivity based on patent protection into the 2040s. And that is a unique situation that we have. We're moving into- towards Phase III now, with almost 20+ years ahead of us with patent protection.
The lead indication, as has been alluded to by previous speakers, is levodopa-induced dyskinesia, and you've all understood that there are, of course, other opportunities. I also want to take you through the background to where we are right now and showing what we've generated over the past few years. Now, we're looking at a quite large body of evidence, clinical evidence, supporting mesdopetam as a novel treatment for dyskinesia in Parkinson's. We started out with the standard Phase I studies in healthy volunteers, single-ascending dosing, multiple-ascending doses. We could conclude that we had a safe and tolerable compound in our hands, and this is going back to 2016 and 2017. And we also could learn that we could give this repeatedly with predictable pharmacokinetic properties.
So this is one of the key issues or key elements of this program. With mesdopetam, we have an extremely predictable pharmacokinetic profile. Then we went into a small Phase Ib study in Parkinson patients here in the Stockholm-Uppsala region. Very skilled clinicians in the region supported the study, collected a number of patients, and we explored a number of doses and to look at safety and tolerability, pharmacokinetics in the intended patient population, that is the Parkinson population. It could have been different from healthy volunteers. It turned out it wasn't. The same kind of properties in Parkinson patients as in healthy volunteers. And in this study, we also collected information on movement, effects on movement, and we could see that we have a quite strong effect on dyskinesias in this trial.
We used the Unified Dyskinesia Rating Scale, the UDysRS scale, which is the scale preferred by the FDA in that study. Then we moved to a larger, Phase II study, where we looked at an expanded population. We kept on looking at safety, tolerability, expanded on the pharmacokinetics in that study, but also collected additional information on the scales that we want to use in the pivotal trials, but also learning a lot about the scales and how they behave in the clinical testing situation. We could conclude that we had a clear and apparent antidyskinetic effect of the drug in those studies as well. So Phase Ia/b, Phase IIa, indicate that we have a safe, tolerable drug with good pharmacokinetic properties, with antidyskinetic profile. Thus, we went in to do a proper dose response study.
We had in these two first clinical trials, we have iterated the doses a little bit to be sure that we don't miss the area, the dose range that we want to study more carefully. So in Phase IIb, we designed a study with four arms, where we had placebo, 2.5, 5 and 7.5 milligrams BID. So three doses and placebo. And this study read out in January this year. We communicated results from the study. Once again, safe, tolerable. We have expanded the safety database now quite to a quite large population of patients from different regions of the globe: US, Europe, Asia.
In parallel with the Phase Ia behind Phase IIb, I need to mention that we did a number of Phase I studies in collaboration with Ipsen. Necessary studies, which regulators require, that you do before you enter into Phase III or pivotal trials. Drug-drug interaction, we're looking at how does other drugs affect the effect and the pharmacokinetics of mesdopetam and vice versa. Then we look at the human mass balance study, which is a complex study where we use radioactive material to study the distribution of the drug in extreme detail in the body and the excretion from the body. This is also necessary studies to do. And then we did a study looking at the PK in different genetic populations.
Here was a study in Asian populations versus American population. Caucasian American population, I should say. We found no differences. So all these Phase I studies panned out with fantastic data in support of the use of this drug in further studies. Also, what the Phase I studies do, they actually expand the number of patients. They allow us to expand the number of patients we can include in the forthcoming studies. We've had restrictions before, which we now can lift in terms of recruitment. The study also gave us a clear and significant effect on very important aspects of anti-dyskinetic effects. Does this work, this pointer? Yeah. So, I will focus on the full analysis population.
We've discussed this data in recent presentations, but I will look at the full analysis population, which is what is commonly referred to as the ITT, the intent to treat population. Here we saw it on the primary endpoint; we didn't see a much effect, but a clear dose-dependent effect of the drug. On the other hand, on the regulatory preferred scale, the Unified Dyskinesia Rating Scale, we have significant effects, nominally significant effect across the doses. These are effects that are large. They are actually larger than has been published for other treatments in the field, or one other treatment in the field, I should say. If one looks at the specifics of some subscales of the Unified Dyskinesia Rating Scale, this is the objective, so-called objective score.
This is a score that the physician rates when he has his patient in front of him. So that's the objective score. And we have a clear signal, 6.8 points from baseline, and I think 4.2 versus placebo. And this is larger than has been published for, for instance, for amantadine extended release. So a really nice effect we see here. And in addition to this, we see this: a clear and sustained dose response on OFF time. And this is an extremely important aspect of the pharmacology or the effects of mesdopetam. Combining antidyskinetic effects with improvement or reduction in OFF time is a very important property of the compound. It's both antidyskinetic and antiparkinsonian.
If you look at the patients that actually followed the protocol fully, this is the PP population or the protocol-compliant population. We, of course, get larger effect sizes, and still the dose response is retained. We have, of course, a larger effect, and this is probably more closely to the maximum or true effect of the compound in the population. So with this, we can compare the results that we have here in front of us with the Phase IIb study, and compare that to what the FDA said before. FDA is the only regulatory body on this earth that have approved a drug for dyskinesia before. So this is. We are coming in with a second attempt here.
If you go back and look at what was used as arguments for approval in the file for amantadine extended release. First of all, the Unified Dyskinesia Rating Scale, and then a subset from that scale, which we published on the poster that we had at MDS in Copenhagen, which can be found on our website. So we can go back and look at that. That's also significant in our study, almost significant in our study. And then we have some safety endpoints, and the important with this is, these endpoints here, the OFF time, the MDS-UPDRS, is that they should not worsen. There shouldn't be a worsening. They can be improved, that's fine, but they shouldn't worsen. And we actually achieved those goals.
And when you look at B ad ON time , that is on time with troublesome dyskinesia, that is reduced also. So that. And then as a secondary, optional endpoint, they used Good ON time, and we also have an improvement there. But if you look at the, that's the ITT population. So, already in the ITT population, we actually achieve what is necessary in this Phase IIb study, what we believe is necessary. And then if you look at the per-protocol population, we actually tick in on all these requirements and actually spill over with an improvement on OFF time here as well. So this is the reason why we have such a firm belief in the project as such and in the compound.
With that short, brief summary of the data, I would like to invite Karl Kieburtz, Professor of Neurology, who is now working together with us in devising the regulatory strategy for mesdopetam. And you're gonna talk a little bit about regulatory aspects of developing Parkinson's drugs and especially mesdopetam. Thank you.
Mostly indeed. Thank you. Nice to see everyone. I'd like to talk about planning for Phase III, especially from an FDA regulatory perspective, and just talk about these studies or these types of meetings that happen in FDA drug development, so-called Type B meetings. They happen at three important stages in drug development. One, when you're about to go into humans for the first time, that would be a pre-IND meeting. Two, when you're about to go into pivotal studies, that is you've done your Phase II and your learning studies, but you're about to do the definitive studies to demonstrate benefit, you have an end-of-Phase II meeting. And then lastly, a pre-NDA meeting when you are about to ask for regulatory approval. These meetings are increasingly important at the FDA.
It used to be you were able to get in-person meetings, but these Type B meetings are now almost the only meetings where you get live interaction with in-person meetings with the FDA. So these are really important because you have a chance to present your case and get their feedback. Most other meetings now are so-called written response only, where you put in a briefing book and you get back written comments but don't have any chance for live interchange. This End of Phase II meeting, which we planned, is really critical because it is the opportunity to get consensus with the regulators about what you need to do next on all parts of the clinical development. So that's the clinical studies, non-clinical toxicology, chemistry, manufacturing and control issues, and clinical pharmacology.
You need to have this meeting to align with the agency about what you've created so far and what you need yet to create to have a package which is approvable. IRLAB is really in a very strong position about what they have in terms of clinical data, as you've just heard Nicholas describe. The end of Phase II meeting gives you an opportunity to present those data and talk about what happens next, what's the design of a planned pivotal study, as well as if one pivotal study might be enough for approval. Talk more about that in a moment. Once you've had an end of Phase II meeting, you also have the opportunity to ask for what's called a Special Protocol Assessment, which is also referred to as a SPA.
After end of Phase II, you can do one of these, which is to submit your planned pivotal study for review. A SPA connotes the following: If you get agreement on the protocol, that means if the study is conducted as described in the protocol and generates positive results, the FDA will consider that substantial evidence of efficacy. So if you achieve agreement and you conduct that study and you have positive results, the FDA has pre-specified that they will accept that result as evidence of efficacy. This is something you can do after an end of Phase II meeting.
Having a clear consensus after the end of Phase II meeting about that design, potentially with a SPA, decreases the likelihood you will either have trouble at the time of NDA submission, which generates a so-called RTF, Refuse to File response when you submit, and they say, "No, you can't file it." Or once you've filed a Complete Response Letter, which is, "This is not sufficient." A Refuse to File is without review. It just means on its face, it does not meet criteria for an NDA, and the CRL is the response you get when, with review, it's found to be deficient. These are things you definitely want to avoid but have happened increasingly frequently, especially in the Office of Neuroscience. So having this end of Phase II meeting, potentially with a SPA, allows you to avoid the likelihood of those disagreements.
This end of Phase II meeting cannot be requested until you're prepared to submit your package, because the way the timeline works, from the time your meeting request is accepted to the time you have to submit your full documentation, all the data you've created so far, all formatted into questions for the FDA, you it is too short a time frame between meeting acceptance and time to submit the package. So you can only really submit the meeting request once you have your meeting package prepared, which is a lot to do. What about a pivotal study in PD LID or in dyskinesias? Unlike many CNS trials, a pivotal trial in PD LID is intended to demonstrate clinical benefit. So lots of CNS trials are about not making people better, but making them worse more slowly.
These are the things we've seen mostly in Alzheimer's disease, for example, with anti-amyloid treatments. People do not immediately get better, you just change the slope of their decline. Those studies need about an order of magnitude more people, and you need enough time for people to decline. So those studies often are 18 months to 2 years in duration. Unlike that, treatments that in Parkinson's disease that are designed to drive improvement in advanced patients need only be 12-13 weeks in duration. So these are relatively short studies with not that many patients. Despite the shorter trial duration, the indication for treatment is not somehow time-limited. So opicapone, a recently approved COMT inhibitor, had 12-14 week studies, but the duration of treatment is indefinite. So even though they're short trials, the duration of indication is quite long.
So a pivotal trial to demonstrate improvement in dyskinesias as well as in off time is under 100 patients per arm. So this, of course, is part of what we'll be discussing with the FDA at an end of Phase II meeting. Another key thing is what's the dosage? And our lab has really generated enough information to be clear about the dosage. People with Parkinson's disease have been at higher dosages than this, and also we've seen the data with lower dosages, and this appears to be a reasonable dose to bring forward into pivotal studies. FDA has already told us, and there's regulatory precedence for the UDysRS to be the primary outcome measure, this Unified Dyskinesia Rating Scale, and the specific elements of it that they wanna see, and the precedents around this for extended release amantadine.
So the details about these things, the entry criteria, the outcome measures, study duration, and the analytic approaches would be the context, part of the context at the end of Phase II, and definitely part of a SPA, if we pursue that. What's the evidentiary standard for approval of drugs at the FDA? Well, since 1962, there's a so-called Kefauver-Harris Amendment, was when the FDA changed its stance on drugs needed substantial evidence of efficacy, and typically, that means two pivotal studies. However, there's a strong movement in the FDA Office of Neuroscience, which where Parkinson's disease finds itself, to look at alternate pathways, and there's two main alternate pathways for approval. One is accelerated approval. This is approval of drugs based on biomarkers, not clinical outcomes.
We've seen this recently with aducanumab and subsequently with lecanemab for Alzheimer's disease based on the biomarker of PET imaging for amyloid accumulation. Also, tofersen is approved based on neurofilament light and hereditary ALS. That kind of approach is not appropriate here. There is no biomarker measurable regarding dyskinesia, so accelerated approval is not possible. But there is another pathway about a single study with confirmatory evidence, and the FDA just released a guidance on this approach. But this is the kind of approach that led to the approval of Relyvrio, Amylyx's drug for ALS. Recently not approved in Europe, but approved in the FDA on this basis of single study with confirmatory evidence. The nature of confirmatory evidence has been hotly debated over time.
People weren't really sure how to approach drug approval this way, but this recent guidance in September from the FDA lays out exactly what can constitute confirmatory evidence, and it goes so broad as to even possibly include non-clinical data from relevant animal models. But certainly, the data that have been generated from the Phase IIb study on UDysRS could be considered that kind of confirmatory evidence. You could not consider that study a pivotal study, in my view, because it was not predesignated as the primary outcome measure, the diaries were. But in the primary analysis population, UDysRS was statistically significant at the 7.5, so that could potentially be used as confirmatory evidence with a single additional pivotal study.
We'll ask about this at end of Phase II, and if additional pivotal study is required, that could be duplicative to what we've just described or potentially take another design. But we also will need to talk about a long-term safety study to generate sufficient patient numbers of exposures, which have ICH guidelines about how many patients have to have exposures. Typically, 100 patients followed at the maximum dosage for at least a year. So that's a lot of regulatory talk, speak, which I think is really important in the next step for IRLAB. But I think it's also worth taking a moment to think about what's the clinical utility here. And I would just like to underscore the idea that there's a drug that treats dyskinesias and improves Parkinsonian disability is exceedingly rare. We obviously only have one approved drug.
It's sometimes hard to realize that in clinical practice, one is in this yin and yang of giving enough drug to treat someone, levodopa and dopaminergic drugs, but balancing that against the side effects, dyskinesias and other complications being part of that. And we're constantly trying to balance how much drug can we give without driving people into too much complication. But here's a drug that does both. It is able to decrease dyskinesias and make people better. Most of all the drugs we have for improving insufficient treatment worsen dyskinesias. So to actually have a drug which does both things would be extremely unusual. Obviously, we only have one other case, and on top of that, this is a drug that is exceedingly well-behaved.
Nicholas and Gunnar already alluded to that it is well-behaved in terms of its pharmacokinetic profile: predictable, stable, reproducible, and its safety profile is excellent and doesn't compound on top of any of the safety profiles with other dopaminergic drugs. So it has a strong efficacy profile, as well as a good safety profile. So a safe and well-tolerated drug, which has the efficacy potential, similar to what we've seen in the other approved compound, would be really highly sought by clinicians, patients, and families. So I think there's a real therapeutic potential here, which we haven't seen in quite some time in Parkinson's disease. So I think that's it on that, but stay put. I'm just gonna hand over.
Thank you so much. We've done very well, which I'm happy for, and we actually have time for a question or two for the local audience here. Could we have a mic to the gentleman right there, please?
Hi, Gonzalo Artiach from ABG. One question regarding the data that you have generated in the Phase IIb. If I am not wrong, the positive results that you see now, for example, in Good ON time in patient diaries, it's with when you adjust the population for 16 hours awake and 8 asleep. Is this something that the FDA could consider for a future secondary endpoint in the analysis of a Phase III? Or... Yes, a little bit on this adjustment of the data.
Yeah. So the FDA, analysis of diary data, has two major rules. The first one is that, in a diary, you complete for 24 hours, 30-minute periods across that 24 hours. So for every 24-hour period, you have to have 48 entries on a daily diary, that 44 of those entries be completed. So you can only have 4 missing 30-minute. So any diary with less than 44 entries is considered missing. So that's one they require. And the second thing they require is standardization to a 16-hour day. So this analysis is the FDA-required analysis for standardization to a 16-hour day. So that's-
Thank you very much.
Yep.
I have another question down here. Rutger.
This is a question rather regarding the pharmacokinetic profile. I think you intend to dose mesdopetam once or twice daily. But could one expect a better outcome of Good ON and OFF time with a slow-release formulation that gives a very, very even dosage during the day?
Yeah. I'll say it is 7.5 milligrams given twice a day, so twice during the day, which leads to consistent D3 antagonism. Could you get a more consistent antagonism receptor profile with an extended release? I-
I can make a try. It's a common feature that sustained release formulations may have better clinical utility. We are not sure that is the case here. But of course, that's something one should consider for lifetime or lifecycle management, et cetera. But it's not, it's not a thing that we have in the pipeline right now, although we've been looking at it. Now we know that twice daily for these patients is quite manageable. Even more than that, actually, it's manageable for Parkinson patients. So from the practice for the patients, it really doesn't make the difference. The question is whether it should be give a better efficacy or not, and that is not easy to answer. You'll have to make a trial.
... and then just a question on the end of phase two FDA meeting. We haven't heard anything from the company lately. You haven't put together this book yet, I believe, so we don't know when that meeting can be expected.
We're working on the book now. With IRLAB and myself, my company, Clintrex, as well as with PPD, who's a group, used to be called the Weinberg Group. We've worked with them with a lot of other regulatory submissions. Part of that is having all the data in hand, which requires some of the data previously held by Ipsen to be in IRLAB's hands and for us to digest it and put it into that format. Our intention is to have that request in this quarter and potentially that meeting shortly thereafter. There's a lag, and as you get closer to the end of the calendar year, the FDA sometimes pushes when they have their in-person meetings, but that's job number one. I see Nicholas pointing at me and Gunnar also, but that's the plan, as rapidly as possible.
Mm.
Just one additional information on this topic. When we struck the deal with Ipsen to get the full securement and access to mesdopetam, we also agreed that the transfer of data from Ipsen should be completed by end of this month. So, so first, of course, as Karl pointed out, we need to get access of all the data, then we bring together things in the briefing pack, and as soon as we have it at the stage where we know that we could submit it in a very short time period, that's the time when there will be a contact with the FDA.
I think we have a very good handle on the phase 2b data, but there's some phase 1 data. We have to be able to present and speak to all of that at the end of phase 2, so that we are very clear on what is the incremental data needed at NDA. And if we can't present those data convincingly, they won't agree to what the next incremental step is. So I think it's very important to have all that data in hand and present it properly in that book. Otherwise, we run this risk later of having misalignment of expectations.
So, to summarize, we're working on it. We will, of course, inform when we have something to inform, but our ambition is to have this as soon as possible. And, one thing that has been left out of the discussion today is that FDA, when they give us a time for an End of Phase II meeting, that's 60 days after they have, they have, announced that we get the time slot. So there's a two-month period where they review the data as well. So it's our work, plus their two months, that that's necessary here.
Hi, Fredrik Thor from Redeye. You mentioned this movement for this second approach. It's not accelerated approval. Could you elaborate a bit on how big indications could it be used for? Is it... I mean, ALS is much smaller, of course. How applicable is it for a large indication, let's say, Parkinson's?
I would say, like accelerated approval, if the feeling is that two pivotal studies could be done without a stretch, then they would prefer that approach. But I would say, remember dyskinesias, especially in the setting of the Gocovri approval, was done under orphan designation. They're no longer designating dyskinesias as an orphan condition, but it's right at the edge. So this is not perceived as a large indication, and it's understood this is a complicated and underserved population. So I think ALS is an example of where it's a more natural fit because of its rarity, but this is also close to a rare condition. So if it was general treatment of Parkinson's disease, I think it might be harder 'cause it's widely perceived that you can do those. But let me just argue against what I just said.
The accelerated approval was done in Alzheimer's disease, which is a very common condition. So there is no requirement that these alternative pathways be only in rare conditions. You just have to argue why you think the evidence is compelling as it stands. By statute, one study plus confirmatory evidence is a viable pathway, so it doesn't need special conditions to be utilized. It just has to be that confirmatory evidence is compelling enough to stand for the second pivotal study, and this recent guidance has made it quite open what that might be.
To have evidence. The one pivotal trial plus the evidence you already have, what kind of? If you look at the phase two B trial, what would be enough good data from a phase two B trial to be able to use it?
To me, the UDysRS is the primary outcome we're gonna use in phase threvrie, UDysRS. In that study, in the primary population, the ITT population was statistically significant. The only glitch is that it was not pre-specified as the primary outcome. So in my view, that makes it very strong as fitting this confirmatory evidence description.
Thank you.
Yep.
Okay, I'd like to shoot the question on my own. Looking at the data from the Phase IIb trial, it's fairly evident when you compare the ITT population to the per-protocol population, not only does the absolute effect go up, the placebo effect went down a lot. So what I was thinking about is, okay, so could it be that the patients who are not able to follow the treatment per protocol are perhaps not as, you know, diligent or able to recollect in their diary taking or something like that? Or, you know, why do you think this effect was there? Because it, it... I have another question-
Ye- yeah
-later.
I think it may be useful-
Yeah
... to look at that as we say that, because-
Yeah, you see-
This-
this placebo compared to
Here
-there. Yeah.
Yeah. I would argue that this is getting more bigger than that is getting smaller.
Mm-hmm.
I think that's because you're actually seeing the diaries from people who are taking the dosage of interest.
Yeah.
I think it's more driven by this getting taller than this getting smaller. But indeed, in a per-protocol population, you have people who are able to adhere to the protocol requirements. These diaries, although it sounds quite straightforward, is not so straightforward.
I know.
So, getting it done properly, I think that's why you're actually seeing some of this evening out, because 2.5 appears to be at the cusp of being an ineffective dose. You're seeing more parallel between placebo and 2.5 here. So I think this is right sizing, and this is probably going up. You don't see, I would just say, you don't see such a huge magnitude change in the objective score.
That's also my comment.
Because this is physician-directed as opposed to diary. Has less to do with ability to comply with the requirements. It. They're using their skills. So it's a little... It does enhance a bit more, again, I think, because these are people who are actually getting the 7.5, but you have less of this being able to complete the task-
Mm
... issue embedded, which is just how diaries work. It's-
Yeah, and especially here, I mean, the placebo effect goes away even more when it's not sort of diary related. So that comes to my follow-up question. I mean, this is—I mean, we know diaries are tricky. There's a debate in the industry going on. There's companies like Roche out there, you know, pitching and selling their own solutions and so on, and there might be other things happening I don't know about.
Do you feel that there are any sort of new tools out there that you could, you know, incorporate into the Phase III design to be able to minimize sort of this challenge of getting any, you know, even if it's a secondary endpoint, you know, diary-based measurements correct, and that you can capture the actual data in the best way, that you, you know, can improve the design in Phase III over Phase IIb?
I think the short answer is no. I think there's lots of interesting things being developed. I can talk a little bit about them, but I don't think any of them are actionable yet. That is, the FDA doesn't know quite what to make of them. I think we will have a requirement, well, we've already heard from them in Type C meeting, that this is the primary they want.
Yep.
They want to very much know about this. From their perspective, though, that it's that that bar isn't going the other direction. They wanna make sure that you're not achieving this by making people have more off time. We're now on the path to saying we want to get, like, extended-release amantadine has-
Mm
... a description of this and this. So I think we're gonna need diaries and UDysRS. Are there other measures being developed? I'm not so sure about the Roche app, frankly. I mean, I've spent a lot of my career helping develop iPhone-based remote assessments, but I think there are emerging remote assessments, including radio frequency transmitting in the home, where you can actually see how much time are people asleep, how do they move in their native state, in their own home, how much time are they sitting, how much time are they standing? I think these kind of things are gonna take the place of these rather cumbersome, every half-an-hour diaries eventually to say, just how well are people doing in the native state then coupled with an objective?
I think that will be the pairing in the long run, but those measures are not quite there yet, I wouldn't say.
Because it seems to be both capturing the data is one thing, but also making sure that you can increase compliance as much as, you know, possible in the setting.
Yes. Well, I, I think frequent touch points also helps people, especially here, regarding compliance, where people are on multiple medications. Using remote assessments to encourage people to stay on their medications, address their problems, will increasingly be the case. I think these kind of objective, quantitative measures will still require in-person visits, but we're expanding a lot of trial methodology to include more remote assessments, which is partly about hand-holding and encouragement. Fortunately, these studies are not that long, 12 weeks, but I think anything that helps with compliance and integrity of the data will help.
... Okay. Thank you so much. Very interesting, and we'll be circling back to these questions, potentially, and we'll see Professor Kieburtz again in the panel discussion in just a little bit. But before that, we're gonna welcome, Joakim Tedroff, the company's Chief Medical Officer, back to speak a little bit about pirepemat.
Thanks. Thanks very much, Torfgård. Well, so I'm gonna talk a few words about pirepemat, our Phase IIb project running at the present, and which has a very interesting and new indication, falls. As I told you earlier, Parkinson's disease is the number one falling disease and has no treatment to reduce falls, which is... falls is associated with a lot of poor quality of life and fear of falling and reduction for the patient in various ways. There's been quite a lot published around falls in Parkinson's disease, the prevalence, and it is reported that about 70% of all patients with Parkinson's have at least one fall a year, and 45% fall recurrently, that is more than once a year. And actually, falling is associated with a poor life expectancy.
The median survival in patients that have recurrent falls is only six years. Now, why do patients with Parkinson's disease fall? Well, also elderly people fall, and, you know, falls and fractures, many orthopedic surgeons do a lot of surgery due to falls in elderly. And patients with Alzheimer's fall more as well. Patients who have cognitive impairment generally tend to fall more, and the same for Parkinson's disease. I mean, the underlying background for a fall can be very complex. There are many players around balance and maintaining posture. But one thing that stands out for Parkinson's disease is that patients with Parkinson's disease, they have poor ability to harbor cognitive loading.
That means if they have many things going on at the same time, many, many inputs, they generally tend to lose their balance. So there's a theory called Posture Second, that if you have cognitive overloading, the body loses its ability to stand, and the patient falls. So if you look at patients with Parkinson's who fall, about half fall when they walk and half fall when they stand still. And usually, it happens in situations where there are complex environmental factors around it. So needless to say, a fall is associated with a lot of morbidity. Patients may fracture themselves, injure themselves in various ways.
If a patient with Parkinson's is hospitalized, this hospitalization takes much more time, almost double the amount of time, as opposed to an age-matched person who hasn't Parkinson's disease, because it's more tricky to do surgery, rehabilitation is longer, et cetera, et cetera. So falling is a great problem, and there's really nothing, not much we can do about this. So how did we come about, you know, treating falls with a pill? It, it's a bit counterintuitive. Usually, you have physiotherapy, you have sticks and rollers and all that sort of things. But, as I alluded to, falls are associated with poor cognitive performance and poor ability to load cognitive demands. And what we've done... And, and pirepemat is a drug that affects cortical functions, the parts of the brain where cognition, executive function, et cetera, is harbored.
And what we've done with pirepemat so far, we've done a SAD and MAD, single ascending dosing, multiple ascending dosing, sort of Phase I. And we've done a Phase IIa study, which we published in Movement Disorders in patients with Parkinson's disease with dementia, and where we added this drug, pirepemat, on top of otherwise stable antiparkinsonian medication. And we've started a Phase IIb study, where we have found the doses to be used from the Phase IIa study, and those doses are employed in the current Phase IIb study. And we are measuring falls frequency, postural dysfunction, balance, cognitive functions, and also general mobility. And just a few words on what we discovered in Phase IIa.
It was primarily a study aimed at studying the tolerability and finding a dose that was reasonable, reasonably tolerated and had plasma concentrations that were in an effective range. But when we mined the data for efficacy, we could see that pirepemat did very little to the key symptoms of Parkinson's disease: tremor, rigidity, and bradykinesia. Those are the items that levodopa works very well. But rather on postural dysfunction, the axial motor symptoms, which are not treatable with L-DOPA, in patients that fell, we saw a 50% reduction in the rating scale in the question relating to falling. Patients fell less. And you didn't see much of a difference in patients treated with placebo. And also, I think one piece of evidence that pirepemat actually-...
did affect those systems that we wanted it to affect, was that we saw a statistically significant improvement in executive dysfunction. We administered a computerized test where patients were asked to stack colored balls in certain positions, in certain and it, it's a very complex test where the patient have to think about how many moves you have to make to stack these colored balls in a certain-- in certain positions. And, in patients with treated with pirepemat, they did this faster, and they did also did more accurate predictions. And so the latency to correct was faster, and that was statistically significant. And that shows that pirepemat actually works by improving cortical function, which is very important in order to maintain posture. So what we have started is the REACT- PD study.
It's a study, 12-week treatment, three doses, placebo, 300 milligrams daily or 600 milligrams daily. And this medication is taken three times daily on top of otherwise stable medication. We are assessing, we are making clinical assessment at regular intervals. Patients and caregivers are filling in diaries every day, where there has been a fall, where there has been, injuries, et cetera. And if there hasn't been a fall, they are obliged to fill in a diary anyway, so they don't forget. And then we harvest these diaries at every visit to the clinic. We started the study in Q1 2022, and we had activated all clinical centers by now. We have 38 centers in France, Poland, Spain, Sweden, Germany, and Netherlands.
Completion of patient recruitment has been aimed to end of 2023, and top-line results by next year. So 6 countries are recruiting for this study. I say it's a study which is not only measuring falls. As I said, we measure balance, we measure cognitive functions, and also safety assessment. So it's a quite challenging study for both the clinicians and the patients. The patients that are recruited are obliged to have a certain degree of cognitive impairment, and also at least 2 falls per month, which is high-frequency fallers. Okay, thank you. I'll leave the word to Nicholas for the next talk.
Yeah. We'll go on with a few more words on the preclinical programs. We talked about the most mature programs, the Phase III ready mesdopetam, the ongoing study with pirepemat in Phase IIb. And a few words on the preclinical assets that we are developing. Both Gunnar and Peter talked a little bit about these assets as well, so I won't dwell too much on them. So these two... these three programs, so if I talk about 757 and 942 first, these are two assets where we are building on the knowledge we have generated to some extent on mesdopetam, but perhaps even more so on pirepemat, where we see opportunities in neuropsychiatric aspects of Parkinson's disease or neurodegenerative disorders in general.
So these two assets have been now brought through the preclinical development towards Phase I. And with 757, we expect to have the data package ready for Phase I by the end of this year. For 942, we are planning to do the regulatory tox studies during the spring next year, and have it ready for Phase I during the year. When it comes to 1117, we are currently developing the large-scale synthesis methods for this very, very interesting opportunity to be able to go into the regulatory pre-IND studies that is necessary. We expect to be able to complete those studies during next year. Peter talked about the opportunity here, and these have large patient populations.
One should remember that, for instance, apathy is prevalent in all neurodegenerative disorders. Between 20%-80% of all patients have this problem, and there is no treatment. So there is a big interest around those, those type of assets, and we have an ongoing discussion right now with MSD Otsuka, to see if we can work together on development, the further development of 757 and 942 . In addition to that, we have also been discussing with different types of supportive organizations, among them Michael J. Fox Foundation, who also expressed a quite significant interest in 757 and 942 during the AD/PD meeting in Gothenburg last spring. We've talked about the properties of these molecules.
We haven't said a peep, except Gunnar, about the discovery methodology that we use. And we've talked about the utility of our discovery engine many times before. But the fact that we have such a broad and such a wide pipeline within Parkinson's disease is a consequence of our discovery engine, the ISP, the Integrative Screening Process. Which uses an advanced systems biology approach in the discovery and in the design of the molecules, combined with mathematical modeling such as machine learning, et cetera. The really important thing with this, besides the fact that we are quite different in our approach to discovery of molecules, is that we find first-in-class compounds.
As you may recall, both mesdopetam and pirepemat have been named as they have because they are first-in-class molecules acknowledged by WHO INN. We also get strong IPR, and for all the assets we have shown today, we have patent protection into the 2040s in our hands. We also see, based on statistics going back in time, we also see that the probability of successful phase transitions is slightly higher or actually much higher than industry standard. And this is a slide we've used sometimes, showing that the likelihood of moving from discovery or preclinical to Phase I is 50% with our assets, and then 35 in terms of the standard, industry standard. And moving from Phase I to Phase II, we also have a higher likelihood of transition than the industry standard.
Summing this up actually makes a quite large difference, which should be able to be translated into money, actually, at the end of the day, in terms of saved money and gained money. So, with that, I think it's time for the panel discussion.
Yes, and I will soon ask all of you to approach the stage. But if we do that right away, we're gonna block the screen. And I know, Gunnar, we discussed beforehand, and I had asked the focus of the panel discussion will be on business development and some further discussion on regulatory pathways and issues, and so on. And I asked the company to in order to guide us in business development a little bit, to see if you can come up with, you know, comparable deals that you could use as case studies to better describe what you're aiming at. And in order for everybody to be able to see that slide, I think we'll just start off with that, and then we'll ask you up.
I, I should also state that I didn't notice it when I would given my presentation, but I seem to have skipped over slide nine. And in that slide was one important information connecting to this part of the meeting, and that is, during the year, what have we delivered? You have seen all the progress in the-
Bring it, bring it up.
If you have slide nine.
You have it.
I have to.
Okay.
I'll bring it up.
Excuse me for this. I didn't notice it. There.
The end from.
Oh.
Oh. Well, there you go.
There.
Great.
During the year, we have seen strengthening and growth of the portfolio, and with mesdopetam, we have talked about the Phase IIb results, and that we're now preparing to go to an end of Phase II meeting to discuss Phase III program. We've also talked about that we secured the ownership and all the rights to mesdopetam. Pirepemat, running the study, having had the first DSMB review of the data collected so far, and they state to us, "Just continue, run according to plan." IRL1117, a molecule that we selected early in January, and we've talked about that. And then for IRL757, IRL942, we are now in late preclinical development, making sure that they should be ready to go into Phase I.
But then, as I've stated here, that now with this change in the portfolio, we actually claim that we are a world leading position in Parkinson's disease with our project. And then the last bullet here, that is important for the panel discussion, that is that this year has meant a marked increase in our business development activities. And as you've seen from the presentation so far, we have the focus on mesdopetam, a partnership to move into a Phase III program. And then, we have mentioned about the Otsuka or MSRD, a company within the Otsuka family, having evaluated or evaluating our IRL757 and IRL942. And this is really-
Good to have as a baseline when we go into the panel discussion and talk about partnering. Now I need to go very rapidly to the end again. Sorry for this. Here. So I just wanted to give you a flavor of deals that has been made in the area of CNS. And I want to give this because all deals are unique, and that means that you can't predict that a new deal will look exactly like this. So here we have a deal where Biogen made a deal with Alectos. And here you see that this is a preclinical development project. You see up there, the total deal value, $722 million. And then we flip down to the upfront. How can I make this point?
The red button.
Is there a red one?
Yes.
No?
No.
I just wanted you to look at that. Here you see what is very often the case when you're dealing with early deals, that you have a high price tag by dollars, but you have small upfront. So it's what we would call a back-loaded deal. If we then go to the next one, that is when Takeda made a deal with Ovid. Here we have a deal value of north of $800 million. We see that this is a Phase II trial that has been demonstrating proof of concept. This is for a certain type of epilepsy. But here you see a completely different picture when it comes to the upfront, $196 million. So this is a little bit more what we would call front-loaded deal. The third one being Jazz doing a deal with Cavion.
Here you see the total deal value of $312 million. It is demonstrated proof of concept in a Phase II setting, and $52 million upfront. And this, of course, this is perceived as a smaller indication. The movement disorder here, that is tremor, essential tremor, and therefore, the deal value landed at a different place. And then the fourth example, that is when Supernus bought Adamas to get GOCOVRI, the extended release of amantadine. You see the deal value for $50 million. It is a marketed product with $71 million each year, and the upfront, $400. So extremely front-loaded. Most of the money comes at the signature. And this is, of course, something that is always negotiated between the two parties making the deal.
But I wanted to show you this because you can't say that this is the standard deal that is going to happen. It is really so that every deal is a little bit unique, depending on what indication, how much risk has been taken out of the project, i.e., how much of positive data do you have with the compound? I stop here, but I thought it could give a little bit food for thought when we go into the discussion.
Thanks a lot. And now I think if we can, we're gonna turn off that. Thank you. And we'll invite the entire management team and Professor Kieburtz up here. And just to kick off, actually, I remember Professor Kieburtz, of last year, when you presented online, you said that you were using amantadine already 30 years ago when you were training to be a neurologist. And you know, connecting this to the last example that Gunnar shown, the Supernus deal, in which they paid $400 million for GOCOVRI, which up until now, isn't actually selling all that much. It's a formulation of amantadine. But if you were to look at purely the sales of GOCOVRI up until now, you wouldn't be extremely impressed.
My question is really, for every patient out there taking GOCOVRI now, how many would you, just in a ballpark figure, believe are being prescribed amantadine just, you know, off-label or grandfathered or, or whatever, to, to just get a feel of the total potential of the market?
Can I modify the question?
Absolutely, go ahead.
I think just to hark back to 30 years ago, we were just talking yesterday. When you start amantadine, which only comes in 100 mg capsules, you start with syrup, which is 50 mg per 5 mL and half a... That's a teaspoon. Half a teaspoon once a day... and you go to half a teaspoon twice a day, a teaspoon. You gradually work up so that you can actually give 100 mg. About half the people don't make that. And an anti-dyskinetic dose is generally above 200 mg. So the number of people who are on amantadine are probably lower than the number of people who are tried on amantadine and don't make it. And then there's a group of people who you never even start on it because they already have pre-existing skin problems, pre-existing cognitive problems, and you know...
Because amantadine is a relatively dangerous drug. I would tetrabenazine, they, they have this two-edged sword. They can, they can work extremely well in the right people, and they can harm everyone. So you have to be very careful as to how you use it. So I would say the potential population of—Well, the population that's on amantadine versus GOCOVRI is probably more. There's more people taking amantadine because many people who are familiar with amantadine don't see why they should be paying, or Osmolex, which is the other extended-release version, which is cheaper, at least in the U.S., than GOCOVRI. So I would guess there's more people on amantadine formulations other than GOCOVRI. And I would say the actual addressable market, total addressable market of dyskinesias is probably single-digit multiples of the number of people who are on GOCOVRI.
Is that five times, six times? Probably not 10 times, but it's, there's a much larger population addressable than who are receiving GOCOVRI, and even more than those who are receiving amantadine in any form. Does that give you-
Absolutely. I mean, I thought that was, you know, important to discuss just in order to, to sort of give a feel for the size of the market. And even in the early stages of trying to penetrate the off-label use with GOCOVRI, I mean, obviously, somebody thought it was worth $400 million. So-
Yeah
... so it's big. And I see Gunnar here, you know, wanting to jump in, I think.
Yeah, yeah, just looking at statistics, it's the same roughly in U.S. and Europe. We know that any dose of amantadine, and most would probably have two low doses to have the antidyskinetic efficacy, but roughly less than just south of 50% are being prescribed amantadine. And that means that the population is actually not just that you would switch amantadine to our best optimal. It's also to be able to treat those plus 50% that today are not tolerating amantadine.
Absolutely.
Then I can build on that. Sorry. If you have a drug that's antidyskinetic, antiparkinsonism, but tolerability comparable to placebo, this could be a very strong motivation for doctors, patients, patient groups in Parkinson's, which are very strong, to be talking a lot about it and wanting it.
Mm-hmm. Absolutely. And we discussed a little bit. You had the question on the briefing package for the end of Phase II meeting. And, I mean, in a large company, there would literally be dozens of people, excuse me, working for many months on that type of package. I know you're very busy with it. But that kind of package, I mean, obviously, cannot only be shown to the FDA. It can be shown to potential partners as well. And again, going back to last year's presentation, now, this time by the Ipsen representative, they stated very clearly that they were quite impressed by the package and the preparations you had done. I think the phrase you used was, "It was basically a turnkey project." And now, compared to last year, you have the Phase IIb data.
You have a number of additional Phase I studies. I'm sure you've done some extra CMC or Ipsen did some extra CMC work, and so on, which means that on one hand, the package is even bigger. On the other, you did not hit the primary endpoint in the Phase IIb. And you may be looking at another primary endpoint in the Phase III and have yet to do the end of Phase IIb meeting. So in terms of how is these two points being discussed when you talk to companies in the industry right now? You have a heck of a package, but you also have the extra challenge of convincing them that you're gonna have a successful Phase III trial.
Actually, as soon as we went public with us securing the ownership of the compound, we started to get phone calls from companies asking if they could talk to us. We have continued with those discussions, and they are ongoing, with many companies being very interested. Of course, one of the first questions that comes is: Why did Ipsen not go with this? And, I've said it before, and I repeat myself, that we haven't got a clear response from Ipsen on that. But when we look at what happened in their portfolio... It is my own interpretation that this was a portfolio decision within that company because they had three products that had very good outcomes in different things, approval or very good phase three readouts.
All of them being closer to the market, and they were in different disease areas than mesdopetam. When we meet companies that we present the data for, actually, very often, people respond back and say, "Oh, we had no clue that you had so strong data." So that, that is the usual comment. And then, of course, your question to me will be: But why didn't you communicate this at an earlier stage? Well, according to the original licensing agreement with Ipsen, we had no possibility of talking about the study at all, apart from the initial, press release that was sent out early in January. Mm-hmm. I mean, that's-
Can I, can I give a comment also?
Sure. Yeah.
You mentioned that Ipsen called it the turnkey program when we handed it over to them. And actually, reciprocally, we need to acknowledge that we have gotten back a turnkey program from them. They have been extremely diligent in producing all the documentation and the studies necessary for to advance the program, and that's all ours now, and it's basically turnkey. And when you talked about there's a lot of people working in any company, putting together an End of Phase I- briefing book or briefing package, we have the full Clintrex team with us. We have the full team at PPD. That's our agent in the US, our regulatory agent in the US, and the full team at IRLAB working on this.
So we have that mass of individuals and competencies necessary to actually get this briefing book together.
Mm-hmm. But it's, of course, high priority within the company.
Yes, the highest priority.
Mm-hmm.
Yes, and I also, talking about the package and what could interest the partner, last year, we discussed a little bit more potential other indications or future indications for mesdopetam, tardive dyskinesia, psychosis. Had a very interesting discussion with Professor Kieburtz regarding delaying onset of motor disruptions and so on. And some of these indications, you could probably argue, would be fairly, perhaps not affected even by sort of missing a dyskinesia study. I mean, in psychosis or something like that.
Absolutely.
So for the sake of the project-
Yeah
... for the sake of mesdopetam, it would make sense to try to, you know, advance it into other indications-
Absolutely
... as soon as possible. Ipsen clearly said that they were interested in that, but they wanted to have, of course, the Phase IIb data first. I was curious-
Yeah
... did they do any extra, or did they have you do any extra preclinical work or-
Well, we—Yes. What we've done during the course of the collaboration with Ipsen is that we have generated additional, very strong and interesting data on the psychosis side, the PD psychosis side. And, of course, I can't talk very much about it. We were right in the position of publishing papers around this. We've done that in collaboration with academia. So there we have a strong portfolio of evidence that mesdopetam could be a really, really interesting antipsychotic in Parkinson's patients.
Mm-hmm.
When it comes to TD, we have generated more data in preclinical models, which are predictable of TD. What I was-
Tardive dyskinesia.
Yeah, yeah. Sorry, tardive dyskinesia, where we see efficacy. So, in general... And that's on the preclinical side. We haven't done anything more than we have at present. We have an open IND for the psychosis indication in our hands. And we have a protocol for a psychosis trial, which we have agreed with the FDA.
Okay. Gunnar, did you want to comment other-?
No, no, I think that Nicholas covered it in a very good way. I just want to state for the sake of clarity that, of course, the top priority for mesdopetam right now is the End-of-Phase II meeting with the lead indication.
Yes. Yes.
Yeah, of course.
If I might add something in an area I'm not an expert in. The Phase I study is performed, and the CMC work performed also is viable in the other indications, of course.I
Yeah, sure. Absolutely. But thank you. So that's to the size of the package. I would ask you also to... Because you've said it a couple of times, but maybe perhaps not explained why. But you've mentioned the type of partner you're seeking, and it's either a mid-sized pharma or a specialty pharma. So you're sort of leaving out the big ones. And now it's a definitional thing. You know, Biogen isn't as big as they used to be, so to say. Maybe they're a mid-sized now, and so on.
Specialty.
But why did you make this qualification?
I think that it's not us making the qualification. I think it is more what we see when we talk to different companies. Many of the big pharmas have actually left CNS, spun out the CNS divisions into small or mid-sized companies. And we see that most of the hunger and eagerness is actually to be found in the mid-sized companies being on a growing path, but that's our experience so far.
Okay. And so I'd also like to, we said we'd have some more, you know, regulatory discussion because that's not something you get into in a usual company presentation. And to ask you, Professor Kieburtz, with all of your interactions with them, I mean, the division had some-- they got some flak after, you know, the Aduhelm accelerated approval. Never seen anything like it in terms of pushback from physicians, to say the least.
Mm-hmm.
That's one thing. And then they also approved Amylyx ALS thing, which, you know, people also thought that, you know, well, the bar was a bit lower than usually. So it looks to me that, you know, the Neuroscience Division is one of the more aggressive divisions out there in actually trying to get treatments in front of patients. But again, they've had some pushback on that. Where do you see them right now? Where do you see them going?
It's an interesting question. I do think the Aduhelm aducanumab, as you said, generated quite a lot of discussion, I'll say. But the lecanemab approval on the same basis went kind of quietly. Donanemab got RTFed essentially because refused to file because they didn't have sufficient safety data. So they're just going in with a full clinical approval. So I think the novelty of it generated a lot of that. Traditionally, what's now the Office of Neuroscience was separately the Neuro Division, the Psych Division, and the Pain and Analgesia Division are now bundled into this Office of Neuroscience, which Billy Dunn led, who left. And Nick Kozauer, who led the Alzheimer's group, left.
So there's been a lot of change of personnel, although there are remaining people who have probably have been schooled under these individuals and have similar thinking patterns. It's interesting about... Sorry, to go on to sort of, you know, inside baseball, as we say in the US, like all these little details. But the Aduhelm approval based on accelerated approval was driven by the Office of Clinical Pharmacology, whose assessment was that PET SUVR for amyloid was reasonably likely to predict as long as you got to a high enough dose, and that the Neurology Division reasonably likely to predict is a statutory requirement for a biomarker, not validated, just reasonably likely to predict. The Neuro Division took that on, partly under congressional pressure, 'cause there's a concern about the Neuro Division and Alzheimer's disease not responding to public need.
So I think the Office of Neuroscience, broadly written, is now dealing with areas that are perceived as of great public health impact to the nation, the United States. One, neurodegenerative diseases, Parkinson's and Alzheimer's, having a big impact. Two, opioid abuse and dependence falling under analgesia, and that office needs to be as modern and up-to-date and using all the tools to approve safe and effective drugs. So I think that's a shift from the old. The old was that, you know, the Neuro Division was kind of Victorian, you know, kind of eighteenth century, not even, you know, twenty-first century. So I think there's a lot in flux. Anyone who's making a lot of predictions about the Office of Neuroscience is gonna be wrong a lot, I think, but...
I mean, it is really interesting. They certainly seem to be a lot more open-minded than a lot of other of the divisions. But as you said, you can never predict the FDA.
Well, well, well, even, even in the case of Amylyx, having two AdComs, to have two advisory committees meant you went through all that effort to get an advisory committee, and now you're going back. So that's revisiting... That's this willingness to revisit and look at things again. So I think that's new, so.
Okay, so we discussed a little bit what you need to do and the timelines for the end of Phase IIb meeting, and there's a lot of complicated stuff going into that, of course. But just to put the question as simply as possible, what's a really good outcome for you, from that meeting? What do you want from it?
That is to have an agreement on how the Phase III program should be designed, based-
Well, I want a little more.
Mm-hmm.
Size, size, and number of trials and stuff like that.
Well, this is again, pure speculation, but we would, of course, be very pleased if we could agree that one study would be sufficient in combination of the data we have from the Phase Ib, Phase IIa, Phase IIb studies. And that we agree on the size of the safety population that we need to study. And then that we can also be in agreement with all non-clinical parts of what you put into an NDA, so that we are pretty confident that we know what it takes to get to NDA submission, and if data holds, with a good chance to get approval with a good label.
Mm-hmm. And what will you communicate regarding the timelines going into the end of Phase II meeting?
I think that, as we have been discussing, we, of course, need to keep the market informed about the way forward here. We can't wait and say: "Now we've been at the FDA, here's the outcome." Of course, we need to come with interim updates on the progress here. And this is why we wanted to communicate, as we did last week, that we now have a good agreement with Clintrex team, as well as PPD team, working together with the IRLAB team. That was the first important milestone to show that we really now fully up and running in our preparation work.
Okay, thank you. So, with that, we're just seamlessly going to slide into the Q&A session. And before we do, just a second, I'd just like to remind our online audience, we have a couple of question here, here. We have seen them. We'll take the local questions first and see whether your questions get answered or not, and, then we'll come to the online question. But there's still time. If you want to, ask a question, you should be able to, find, a question thing below your presentation. So yep, we'll start right here.
Hi, again, thank you very much for such a nice presentations today. One question regarding partnerships. Again, I mean, so far, the market knows that at least Otsuka has shown interest in your projects. I was wondering if you could comment on, on what are the triggers that, that, yeah, that started for them, this interest in your preclinical assets, and do they have, interest also in, in mesdopetam and pirepemat, or have they communicated anything around your more advanced projects?
First of all, we cannot comment on specific companies and interest in our assets. That would be incorrect. But when it comes to MSRD and Otsuka, they came to us because they knew that we were working on apathy.
Okay.
So that is a simple answer on that one.
Great.
And similarly, for Michael J. Fox Foundation, that was the same thing.
Mm-hmm.
It's initiative from the outside.
Great. No, that's understood. A second question I have is in the pirepemat study. How confident are you right now that you will achieve your communicated timelines for the end of the year?
These are the predictions we have received so far from our CRO on the recruitments and on the timelines for getting the last patients out. We are, of course, keeping a close control of this, and should there be changes, we will communicate that.
Mm-hmm. Great, thank you.
But the goal, in any case, is that we should have the data to be presented later next spring.
Perfect. And one question regarding—I mean, after your meeting with the FDA for end of Phase II, if we are in the scenario, in the worst scenario, let's say, that you have to run two Phase IIIs or two pivotal studies, could you give us some color on what kind of design would you do for these two different studies?
May I just comment? I mean, it's not a disaster to do two Phase III studies.
No, I know.
As pointed out by Professor Kieburtz and by others here today, the fact is that these are quite small studies.
Mm-hmm.
If you listened to what I said about the Phase I studies, they actually expand the patients we can include in further studies. That means that we are unlikely to have the same challenges in recruiting for the pivotal trials as we had in the Phase IIb. You all remember, or some of you remember, the slow progression of the recruitment there. But, so that was just what I wanted to say first. It's not a catastrophe at all. It doesn't take more time. It's just one more study. But do you want to go on, Joakim?
Yeah. Yeah, I can say, I can say that, you know, we pretty sure about what type of protocol we need for Phase III. I mean, it's aligned with what FDA has required. The tricky thing of this project was to find the right dose and to find out whether it worked or not, and now we know the dose. We know it works perfectly fine. We know the inclusion/exclusion criteria, which is also tricky because how you phrase the way you include the patients also has some bearing on the results sometimes.
The label.
And the label. So we are pretty sure about what to do, and if we were to do one or two trials, it's... You can do them in parallel. It's not a big... It's not a huge deal. So it might be so that we wanted to study some different aspects in one of the trials, but nothing is set in stone yet. But we essentially know what to do.
Thank you very much.
I'm jumping ahead a bit in my two questions. The first one is about mesdopetam and other indications like the tardive dyskinesia with neuroleptic patients. Do you aim to treat tardive dyskinesia that are already there, or do you even hope to prevent tardive dyskinesia?
... Do you wanna answer? Yeah, I can answer. The first thing you need to do, if you go in that direction with the TD as an indication, the first and simplest thing is to actually show that you can manage tardive dyskinesia when it's already there. The second thing is, of course, to look at prevention. And we have said in many of the assets that we have, there is an opportunity for prevention. Mestinon pyridostigmine bromide an opportunity as prevention, as Karl alluded to last year, prevention for the occurrence of dyskinesia. But that's a long-term study. The same thing with prevention of the TD. Long-term study, up to 18 months or so, as presented today.
When you try to look at the non-occurrence of things, it takes longer time, and it's much more expensive. So the first step is always an acute effect on the already presented symptom.
May I also remind that the drug is antipsychotic, so it has properties to treat schizophrenia per se, those patients that get tardive dyskinesia. So you can, you can treat both things, both the schizophrenia and the tardive dyskinesia with one drug. So there, there, there's a huge opportunity, needless to say, but it's very potent antipsychotic.
So just speaking for me, not for my colleagues.
We, we, we-
It's interesting about D3, both for schizophrenia and tardive dyskinesia and parkinsonism and and levodopa-induced dyskinesias, that when you have a compound which may address the core symptoms, it allows you to start that before those drug-induced problems begin and treat some of the core symptoms so that you can maintain the standard backbone therapy lower. In both cases, the dosage of levodopa and the dosage of antipsychotic is a driver of the development of the complication. So if you could keep that dosage lower, add the compound, get additional efficacy, not at the expense of the complication, you have a new paradigm for treatment, that once you reach a certain level of traditional, you add this to get more efficacy and to help postpone the complication. Be very interesting. They're longer term studies, but they're analogous co-developments, in my view.
And then even further ahead, about IRL1117. How is it that you already now, preclinically... It's, it's not a bold statement, but it's a bold hope that there will be no long-term complications.
Mm.
How is it possible to not predict, but you know what I mean?
Yeah, I would say predict, because that is what the preclinical work is basically there for. It is there for to predict what's gonna happen in the clinic, and that is a difficult task. As it happens, in Parkinson's disease, there are clear models for these different things or aspects of Parkinson's in preclinical models, which have been translated into traditional effects in patients. So there is a translatability between the preclinical models and the real-world treatment of patients. This just happened to be like that in Parkinson's disease. So what we've done in our own labs is that we have created Parkinson's in a number of rodents, and we have looked at the long-term effect and compared with levodopa. So we've done comparisons with levodopa, and all this will be published soon.
We're working on the publications, so we can jump ahead and show the data. We've showed a few data points, such as the D1, D2 properties, which is necessary, the D1, D2 agonist. We also shown that we have long-term, sustained behavioral activation. But we haven't shown the details of the Parkinson's studies yet, but that will come. And what we've said also before is that we have a differentiation from levodopa when it comes to the complications.
We had a question right over here from Andreas. Sorry.
Thank you. You showed us a few licensing agreements, and some were front-loaded, and some were more back-loaded. Would you say that you have a preference, or is it mainly up to the specific occasion?
Of course, as being the party that outlines something, you, of course, want to have it as front-loaded as possible. But when you're making a deal, it's always two parties, and you need to come to something that is acceptable for both parties. Then, depending on how strong profile you have, you could push it more front-loaded, whereas you have not a strong position, it's usually ending up with a more back-loaded deal. But you can never predict. It's really the negotiation between two parties wanting to do something together.
Maybe a final question. Do you have any learnings from the Ipsen deal, or was that the right strategy, just you were unlucky that they were lucky with other candidates, or?
I think personally, I think it was a very good deal that we had with Ipsen, and it worked very well. And, as I said, my interpretation is that this was a portfolio-
... decision by Ipsen. Now we need to see what we can do in the new situation we are facing. We are, of course, very pleased to see that we have the full ownership of the project, even after the quite large investment that Ipsen did, both through the upfront payment as well as doing the Phase I studies, doing all the CMC work, and so on.
Thank you.
I could also add that we learned a lot from the licensing with Ipsen, and we actually built in functions in that license agreement that we have a huge advantage of in the new negotiations this summer. So, we definitely had learned a lot from that.
Thank you.
Okay, so we're gonna take a couple of questions from the online audience as well, and I think I'll read the first one in full, as it, I think it reflects, the thoughts of many investors. "Thanks for a very interesting presentation. IRLAB's potential seems undisputed, so that is all good. The biggest problem at this stage seems to be financing, and especially so given today's market cap. What can you disclose on the financing going forward?
Uh-
You want me to start?
Yeah, well, I don't think that we can actually disclose any, any details in that matter. Of course, it would be naive to think that we're not challenged by the financial situations, as most biotechs in Sweden anyway, or worldwide today, and the market conditions that everybody knows about, and so on. But I can assure you that we work as hard as we can on all financing opportunities that we have, might it be any kind of share issues, might it be debt financing, might it be licensing agreements or any other financing options. So, we don't leave any stone unturned, so to speak.
And also from a cost perspective, we are spending our money on things that we are confident will increase the value of our assets, and make them more attractive to others. And also making sure that we don't destroy any value in the projects that we have. So we are extremely cost conscious, but we do spend money to be able to preserve the value of our properties or increase it.
Okay. I think that answers one of the other questions I have, but serving on a bunch of biotech boards myself, I mean, the runway, you can only affect in two ways. Basically, you get more money in, or you spend less.
That is simply correct.
It's not that tricky. What can you say in terms of runway? I guess you have a quarterly report coming up soon, so... But, I mean, you had just south of SEK 150, right? Last close over last quarter.
Just north of 150-
I'm sorry
... at end of June. And, the last couple of quarters or 4 or 5 quarters, we've spent about SEK 50 million per quarter. We've stated before that we likely will decrease our cost as we're closing into the end of the year. But, I mean, you can do the calculation yourself. It's somewhere around 3 or 4 quarters from end of June.
But you're not gonna, sort of... You aren't undertaking any sort of dramatic measures as we speak in order to increase the runway. Is that how I should take it?
If we do, we will communicate that.
Okay. All right. We've run over by almost 15 minutes. Yep, sorry, we had an extra question. Can we get a mic, please? We'll take that as the last one from the audience, I think.
Thank you. Suzanna Queck from Handelsbanken. I am just curious in, in terms of antipsychotics, and I've been following, brexpiprazole from Otsuka and Lundbeck, and, they've needed three Phase III trials, and, I mean, it's the only antipsychotic approved in Alzheimer's agitation. But, as a sort of... I don't know how far you can go in terms of a parallel, but, what, what do you see here? And I think specifically one of the concerns there has been the, within the, geriatric population, there's a, a black box warning for all antipsychotics, so that would also be a concern here as far as I can see.
If, if I can start. I mean, we're not pursuing any psychosis, indication right now, actively. We have built a documentation around mesdopetam as a potential antipsychotic in Parkinson's disease, as well as other indications. So, so we don't have any active, work ongoing in, in the clinic. It's, it's an opportunity for, for, the product in the future, as, as, as Peter mentioned, as lifecycle management. Do you want to comment on the black box warnings for, for antipsychotics?
Well, I'll comment about brexpiprazole in Alzheimer's disease also, 'cause my company is very involved in the operationalization of those trials. Those are very complex trials about agitation in the setting of AD, one of which was positive, then the other was borderline, leading to the third, which was also positive. So there's the heterogeneity in that population, in terms of agitation in AD, led to the sizes of those, and they were extremely complicated to do and were well done, I think. That's why you showed a benefit. So I think the analogy to psychosis in neurodegenerative disease is not that strong. It's a different profile, particularly the profile in Parkinson's disease is visual hallucinosis, as opposed to this agitated, delusional state in Alzheimer's disease.
So I think the studies can be quite a bit smaller, depending on the phenomenology of this particular disease. The black box is interesting. It has to do with, of course, this premature mortality in older individuals treated with neuroleptics, which goes all the way back to Clozaril and others going forward. This is a different mechanism than traditional neuroleptics, and it will be tough but arguable to avoid the black box. But I would say this: even if you have the black box, this problem is a huge problem in Parkinson's disease. Two of my patients responded to pimavanserin. It was one of the few times in my 30-year career of taking care of patients that spouses cried with joy about the treatment effect because it completely ablated the hallucinations.
But that only happens in about 1 in 7, 1 in 6 patients, and the rest don't respond. So we need a more effective antipsychotic in Parkinson's disease. And one which might actually improve Parkinsonian features would be, you know, a double win. So I think they're slightly different... Sorry for the long answer, but I think they're slightly different indications.
Thank you.
All right, so, we've had very informative Capital Markets Day, I think. Some good discussions, some presentations. So before we end, I'd just like to invite the presenters, all of you, in case I or the audience have failed to drag or coax any important information or something you want to add out of you, this is your chance.
I just want to thank you for very good moderatorship. Thank you.
That's not important. But if you, if you didn't have anything more important than that, thank you all for taking the time to coming here. Thank you to the online audience for taking the time, and hopefully see you all next year. Thank you.
Thank you.
Thank you.
Thank you.