Good morning, welcome to this update on the mesdopetam project. My name is Gunnar Olsson, and I'm CEO of IRLAB. With me today, I have Nicholas Waters, Head of R&D, and we will take you through this presentation. Mesdopetam is a great opportunity in an area of very large unmet medical needs. It is antidyskinetic, has antiparkinsonian effects, and this coupled with an excellent safety and tolerability profile. On top of this, also significant differentiation versus available treatments for LIDs. We've identified the dose for phase III, the 7.5 mg twice daily. We have an excellent IP situation. We have potential for exclusivity into the early 2040s, and this is a product with great opportunities for life cycle management. The first run will, of course, be treatment of LIDs. Second line could be optimizing of levodopa treatment without driving LIDs.
Third line could be prevention of levodopa-induced dyskinesia, since our animal data indicates also a preventative effect of mesdopetam. Other areas is Parkinson's disease psychosis, and tardive dyskinesia, the type of dyskinesia we see in patients with long-term treatment with neuroleptics, a very large population. It is not just us in IRLAB that believes that we have a fantastic potential. Here I have a quote from one well-known opinion leader in the field, Karl Kieburtz. I read his quote: "I think the mesdopetam data package is one of the most compelling available in the symptomatic treatment of Parkinson's. Mesdopetam has the rare ability to both improve dyskinesia and improve Parkinsonism, at the same time, appears to be well tolerated. I expect this...
I expect it will have both clinical utility and commercial success." Karl Kieburtz, he used to be the chairman of the US FDA Peripheral and Central Nervous System Drugs Advisory Committee. What is the basis for the great potential of mesdopetam? I think it's the clinical data package that we have now with all the good data on safety and efficacy, and it comprises of the full analysis of the phase II-B study data. We have the 3 studies in phase I that Ipsen ran, and the studies that we've previously reported, the phase I, I-B, and phase II-A studies. Secondly, we have a precedent regulatory approval of treatment for PD-LIDs, and our data from the study is in alignment with that approved product profile. Thirdly, we have a very strong IP position.
With this as basis, we have worked out this agenda for today's presentations. Nicholas Waters will take us through the mesdopetam phase II data, and he will also discuss the phase I studies performed by Ipsen. I will then come back and talk about differentiation, commercial positioning of the future product with mesdopetam. I will also take you through some considerations regarding regulatory precedents in PD-LIDs and how this is important for us. We'll come to way forward with the project, and we will end with a Q&A session. With this, I hand over to Nicholas. Nicholas, please tell us about data from the phase II-B study.
Thank you, Gunnar, and thank you all out there, watching and listening today. This is the first opportunity we have since we prepared or presented the top-line results of the phase II-B study that we performed previous years. We are extremely happy to be able to present some more in-depth information from that study. The design of the study, we've discussed that at several occasions before, but as a repetition, this was a placebo-controlled study where we had 1 arm of placebo and 3 arms with mesdopetam, 3 different doses, 2.5, 5, and 7.5 mg twice daily.
We enrolled patients in the trial who have troubles with dyskinesia and of course, Parkinson's disease as a diagnosis. We're looking at the functional impact of dyskinesia in these patients need to have a certain degree of complications.... Then, as a third important requirement, they should be on stable antiparkinsonian treatment, and that is usually a stable dose of or a stable treatment regimen with levodopa throughout the trial, so that we don't get any confoundings due to changes in levodopa treatment strategies. The study was a 3-month study. We had a screening period, which ran between 3 and 1 month, and then we had a run-in period, where the patients were treated.
All patients that were randomized were actually treated with 5 mg the first 10-12 days in the study as a starting dose, and then they received the randomized dose, that is 7.5 mg, 5 or 2.5, of course, blinded. Between Visit 2 and Visit 3 in the study protocol, the patients, and that is between 2 weeks and 4 weeks of the study, the patients were allowed to adjust their dose 1 time, and this was a down titration that they could do during the trial. These are important aspects when it comes to the analysis of the results, which I will show you. The objective here with the study was, of course, to investigate the efficacy and the safety, and further say, build on the safety database for mesdopetam.
We had a long list of endpoints in the study, where we looked at, the primary endpoint was Good ON time based on Hauser Diary that we collect in the study, where the patients actually fill in on a daily basis, several times during the trial, their different motor states: on with troublesome dyskinesia, on without dyskinesia, OFF time and Bad ON time, and sleep. Those are the three things that come out of a Hauser Diary. We use the Unified Dyskinesia Rating Scale, and a number of other assessments were done during the study. To analyze the data or in any clinical trial, what you do is you look at the what is usually referred to as the modified intent-to-treat population.
In our case, we called it Full Analysis Set. The Full Analysis Set was the data we presented in January, top-line results was based on the Full Analysis Set. These are patients who are randomized to treatment and receive 1 or more doses and then have at least 1 post-baseline data generation. This is independent of the actual dose they have received during trial. If they were randomized to 7.5 mg, they are assigned to the 7.5 mg cohort in the analysis, even if they actually reduced the dose to 5 mg during the trial. That's an important thing to remember when we talk about the results. Then we have the.
We will show today some, some data on patients who are in the protocol-adjusted dose set, which we call PS, in this presentation. These are patients that are compliant to the protocol during the study, they take the medication to a very high degree, at least more than 80% of the time, they or the drug that they're given, they take. They also follow a number of aspects of the protocol perfectly. Also, when one analyzes the data, one analyzes the data based on the dose they actually took during the study. If they were assigned, for instance, or randomized to 7.5, and took 5, they will be assigned to the 5-milligram group in the analysis.
Statistical considerations are quite mainstream. We're looking at the least-squares mean differences versus placebo in this trial, using an MMRM model, which is the commonly used statistical models for these type of data. The Full Analysis Set was based on randomized dose, as I already told, and then we had the protocol-compliant subjects were based on the dose that were taken, and also following the protocol. When it comes to the primary endpoint, we published in January, we informed that we actually did not meet the primary endpoint. This graph here shows the Full Analysis Set analysis on the primary endpoint, which was Good ON time, based on Hauser Diary.
The interesting aspect of the Hauser Diary is that when we look at more refined populations in the study, all the way to the protocol compliance studies, we see a consistent dose response of the drug, which was the purpose of the study. And we have a nominal significant effect at the 7.5 mg dose, actually reaching about 1.75 hours improvement in Good ON time in this trial. Despite the fact that we missed the primary endpoint, we actually have an effect on the diaries in this study, looking at the patients who actually took their medication throughout the study and calculating based on the dose they took.
A secondary endpoint in this, in the study, was the Unified Dyskinesia Rating Scale, which has been used in dyskinesia studies over the past decade. This is an endpoint which, or a scale, which has been preferred by the FDA in previous trials and previous approvals. We do see in the Full Analysis Set, as presented in January, we do see a very clear, significant effect on the UDRS 1+ , and the UDRS, I, I have to go back 1 step. The UDRS is comprised of 4 Sections, 1, 2, 3, and 4. The FDA advises sponsors today to use only 1, 3, and 4. Previous approvals have been based on 1, 2, 3, and 4. Remember that when you compare the data we have here with other studies.
We had a very significant, very clearly significant effect across the doses, 2.5, 5, and 7.5 mg in the Full Analysis Set. Already there, we have actually fulfilled the criteria for an anti-dyskinesia treatment. And then looking at the objective part of the scale, which is Parts 3 and 4, these are physician-rated, so solely physician-rated parts of the scale. We also see a significant effect, and this is important. The regulators across the globe wants to see the UDRS in total, 1, 3, 4, but then broken down also into the subsections, and they want to see efficacy there as well. Looking at the PS data set, we see then in an improvement in the size of the effect.
We see a clear dose response pattern across the doses that we have administered during the trial. The effect that we see is clinically meaningful in the sense that doctors around the world has investigated what is the clinically meaningful effect, and we actually passed that bar with mesdopetam, which is, of course, very reassuring. If you look at the objective score, the same thing happens there, slightly larger efficacy in the Full Analysis Set, but also significant effect across doses. On the UDysRS scale, we can be quite confident that we have a clear and unprecedented, I would say, efficacy with mesdopetam.
Another very important aspect of trying to develop a compound for the treatment of dyskinesia in Parkinson's patients is that you do not want to hamper other symptoms of the disorder. One problem that the Parkinson's patients experience during their the course of the disease is OFF time, increased OFF time over over the course of the disease. OFF time must not be increased by a treatment to treat dyskinesia. That's a requirement. In fact, what we see in the Full Analysis Set is the contrary. We do see an improvement, or a reduction in the OFF time, up to roughly 1 hour in the Full Analysis Set that did not reach statistical significant in the FAS. However, it's a clear dose response that we see there.
Looking at the protocol compliance subjects in the study, we actually see a significant effect at the highest dose, 7.5 mg, and the size of the effect is on par with what is perceived as clinically meaningful reduction in OFF time. We've seen approvals actually back in history of antiparkinsonian drugs solely on circa 1 hour of improvement in OFF. Already here we have an effect which is really valuable. Another aspect of drug development, and perhaps one of the most important, is the adverse event and safety profile that a compound has. I introduced here a flowchart of the different doses and the how many, how many patients who came through in the different cohorts.
For those interested in mathematics and doing that, we'll see that the frequency of dropouts during the trial is similar across all dose arms, from placebo through to the highest dose of 7.5 mg. We have a similar number of completers in each treatment arm in this study, which is reassuring from a safety tolerability perspective. Looking more into detail of side effects, and here we're looking at effects that were reported at more than a frequency of more than 5%, or in incidence higher than 5% in the study. Also here, we can simply say that the e-effect of mesdopetam on the side effects side of the analysis indicates that there is no difference from placebo whatsoever.
And actually at the highest dose, the incidence is significantly or appreciably lower than we see in the placebo group. From a safety and tolerability perspective, the drug is really usable in this population. Some strong conclusions that we can draw from the phase II, II-B study is that we do see those response in and clinically meaningful antidyskinetic efficacy across the endpoints that we have studied in the study and the different scales. We see improvement in Unified Dyskinesia Rating Scale, nominally significant and clinically meaningful. We have improvement in Good ON time across doses, although we did not meet the primary endpoint.
We have a consistent dose-response pattern and reduction in OFF across different analysis populations, which indicates that the drug, besides being an antidyskinetic, also has to put potential as an antiparkinsonian drug. We don't see any hampering of normal motor function. We don't see any increases in PD symptoms, Parkinson's disease symptoms. No increase in parkinsonism with the drug, which is, of course, necessary to be able to move this forward. The safety and tolerability profile was on par with placebo at all doses studied, we have a quite wide dose range here, where we can actually treat patients without any risk of side effects or adverse events.
The plasma exposure, which I didn't show on the slide here, but in principle, it's linear and dose dependent, and this is in line with what we have shown before in the phase I studies and published. One of the most important aspects of a phase II-B study and a dose-finding study is to actually achieve, the main goal, to find a dose to study in further trials. We have achieved that goal with the 7.5 mg BID dose, which we think is the best dose going forward with the product.
During the course of our collaboration with Ipsen, which was a collaboration that was really, really professional and very, very efficient in terms of generating data, during the 2 years we worked with Ipsen. Ipsen performed 3 besides developing the CMC, besides producing drug product and API, they did a lot of interesting studies and necessary studies, which are necessary for submission of phase III studies. They did a comparison between an Asian population and a non-Asian population in terms of pharmacokinetic properties. This is a thing you need to do in drug development. Then the conclusion is that the pharmacokinetic profile of mesdopetam is similar in these populations, which is reassuring.
There is also a necessity to study drug-drug interactions, and that is, how does one other drug that patients take in the population affect the pharmacokinetic or the plasma concentrations of your test substance, in our case, mesdopetam? The conclusion is there is a very low risk of drug-drug interactions, and this is really important, but this suggests for the further development, there is no need for additional clinical drug-drug interaction studies, and perhaps more important, no restrictions on the patients that we can include in the studies in the further development. We have a broader, broader set of individuals with PD that can be included in coming trials.
Then, a very important study, the mass balance study, that is a study where you where you really in detail evaluate where a drug goes and which pathways it takes out, into the body and out of the body, if it stays in the body or if it's eliminated fully. The total conclusion from this study was that there was no signs of risk of drug accumulation at all in the body. All drug is excreted over time, and there is no risk for accumulation. These studies are important pieces of the big puzzle of building a file for a future NDA.
The implications, as I've already alluded to, is that we have predictable PK with low degree of variability, and we anticipate a very simple and uniform dosing, that is perhaps the 7.5 mg dose, which allows for a, a low risk of dosing errors since we have such a tight variability in the plasma concentrations after a given dose. Gunnar, please come back and talk about the differentiation and commercial positioning of the compound.
Thank you, Nicholas, for that good presentation. I will now talk a little bit about commercial aspects, and I will focus on differentiation and how we see a future positioning of mesdopetam as a product. I start by just recapitulating the accessible market, and you see here, from some key markets about 5 million patients with Parkinson's disease. We see that a, a proportion of those will develop PD-LIDs, and a proportion of those with LIDS will get treatment. I think that the two key take-home messages from this, that is that the prevalence of PD-LIDs is in the range of 25%-40% of the Parkinson's population.
If a patient develops LIDs, then there is a high likelihood that that patient would want active treatment and also gets treatment for the LIDs, 80%, roughly. Now, to differentiation. I know that this is a slide with lots of data, and I will take you through it step by step. Here we compare our mesdopetam Phase II-B data with your to safety and tolerability with amantadine ER, that is Gocovri. Actually, the amantadine table here, the, the right hand, that is taken from the labeling text in the United States, approved by the FDA. We start here by looking at the placebo groups in the two sets, the mesdopetam placebos, and the amantadine placebos, and you see very low rates of reported AEs or side effects.
That, to me, indicates that we are dealing with pretty similar populations in these two different datasets. We then go to amantadine ER, we see a very frequent set of side effects. One in five of the patients cannot continue treatment, has to withdraw. One in five will develop hallucinations, we could continue the list down. Let's instead look at the mesdopetam active treatment column. Here you see, as described by Nicholas, that our safety tolerability profile is on par with placebo, a very marked degree of differentiation. We should understand that today, amantadine ER is the only approved drug for treating PD-LIDs. We have here summarized some important characteristics or properties of a treatment. I won't go through every single box here.
I think that when we will leave the slides on, on our homepage, anyone could study them in detail. I wanted here to just make you aware of the fact that when we look at this, we see mesdopetam ticking all the boxes in a positive way. When we look at amantadine, as you see, in most of the fields, we see that the drug doesn't match what we think is the ideal position for, for a drug. We do have a very marked differentiation potential for mesdopetam opposite the available treatments for LIDs. The ideal profile for a LIDs medication should actually be a clear antidyskinetic effect, a good safety and tolerability profile, as well as no signs of increase of Parkinsonism.
This is really the profile that you heard being described by, by Nicholas when he went through the data from the phase II-B study. When we put this all together and we think about what would be the positioning of mesdopetam as it hopefully comes to the market, well, we see that this is a first-line treatment of levodopa-induced dyskinesias. It has antidyskinetic efficacy, anti-parkinsonian effect, excellent safety and tolerability profile, and it is simple to dose, and we use it in the broad PD-LIDs patient population because of the predictable PK, no known drug-drug interactions, and no contraindication. Leaving the commercial aspects and now moving into regulatory considerations that we, of course, have been discussed and evaluated as we now see phase III coming up.
Of course, we have then spent time looking into all available, for us, available regulatory documentation from the approval of amantadine ER in the U.S. What we can extract of it, that is the endpoints that was of importance in the product development, and that was then later on approved by the FDA. As primary endpoint, UDysRS Part 1, 3, and 4. Key secondary endpoint, UDysRS Part 1 B, and 4. The safety endpoints, OFF time-... can't accept that being worse. MDS-UPDRS Part 2, again, should not be worsened, and Bad ON time shouldn't increase. Then as an optional secondary endpoint, Good ON time. This is what we have been able to take out from the precedent with regard to approved product for PD-LIDs in the United States.
Let us now see where does the phase II-B data fit into this? As you see here, we have the UDysRS Part 1, 3, and 4B tick, ticking the box, and we have the safety endpoints, the OFF time, the MDS-UPDRS Part 2, and Bad ON time also ticking the box. That means that already now on the fast data, if we can replicate that in the phase III study, we actually fulfill what we believe will be the requirements for registration of, of, of, of mesdopetam. If we now look at this and we take the PS analysis into account, we actually see that we are ticking all the different boxes.
The task for us now, that is with all the knowledge and experience from running these type of studies, we will build that into the phase III program, and we will aim to reproduce what we saw in the phase II-B study. I think that this is time to also have another quote from another well-known key opinion leader that we have consulted and discussed our data with, and this is Professor Warren Olanow. Professor Olanow is a key clinical researcher in the field of Parkinson's disease, with a very special interest in LIDS. He, he just summarized his view in one short sentence: This, this is a really important drug. Now we have taken you through new data that we now, after the agreement with Ipsen, we've been able to communicate, and we are very pleased to do so.
We have already now, of course, started to think about what is the next steps forward. As you all understand, we're now working together with Ipsen to have a rapid transfer of all different parts of the mesdopetam project to IRLAB. We are preparing for an end of phase II meeting with the FDA, that is to define how we should design the phase III program in detail. To do so, we are now starting to prepare a briefing book. That briefing book, we are bringing together in collaboration with regulatory and clinical advisors. We also have support from Ipsen to do so.
When we have that document in place, I should stress here that we now have all the information that needs to go into the document. We don't need to produce new information, we have it now. When we submit that to the FDA, we can also ask for a meeting, hopefully, we get a meeting time then decided upon. In parallel, we will, of course, capitalize on options for financing of the phase III program. Here we will look into all options and possibilities. We will, of course, look into capital market routes. We will, of course, look into business development and partnering routes.
At this early stage, after having the project back, I can't give you more details than that, but we definitely will work on seeing the different options and see what is the best and optimal way forward for us. I should also comment upon the right sound, right side of this slide. Just a reminder, next week, there is the MDS conference in Copenhagen, and then additional data will be presented with regard to the phase II-B study, additional to what you, you have seen here today. Before I open the question and answer session, I just wanted to remind you about some key characteristics of IRLAB as a company. We are developing a portfolio of products that we aim to transform treatments of people with change the life of the Parkinson patient.
At the moent, we have five products from preclinical development up to phase III, ready, project. We are addressing the great ma jority of different complications and symptoms that an individual with Parkinson may have during the full course of the disease. We are addressing things in the early Parkinson individual, as well as in the late stage, disease state. IRLAB, yeah, we have pioneering biology and the unique ISP platform for identification of new candidate drugs. All this is building on the profound knowledge base that has been built around the research group, around the Nobel laureate Professor Arvid Carlsson. Our strategy is very focused. We, we have the very deep understanding of Parkinson, and we are now developing drugs that will help the Parkinson patient. We have validated our model.
We have taken, I shouldn't say we have taken, we've discovered new molecules that we have taken all the way to now phase III readiness. We have a broad portfolio, I, I, I would actually dare to say that I think we have a world-leading portfolio within Parkinson's disease, and we are an organization that is positioned for success. With that, I think it's now time to open up the Q&A session, and I invite Nicholas back here on stage. We will now have the Q&A session in, in the following way. You have been able to send in questions through email. We have Tove,
Hello.
Who is the receiver of all your questions, and she will now address the questions and read them out loud, and then Nicholas and I will see that we are responding to the questions.
Right. We'll, we'll start with some clarifications on the clinical results. We have a question here on: What was the main reason for the dropouts in the study?
They go across a number of aspects and, and not, not always known to us, but sometimes the patients have decided to, to leave the study, and sometimes the physician have decided that the patients leave the study. As indicated also in the slides, there will be more, more details on that in the MDS conference poster. But in principle, there's no, no, no single reason that really can be pinned out. As I said before, the adverse event profile and the safety profile is similar, so there's nothing to do with adverse event or safety.
Is any comment on the dose reductions that have been made?
Equally across, the, the, for the 4 different arms in the study.
Including the placebo?
Yes, the four arms.
Right. Going into the clarifications around the Full Analysis Set, you did mention that a patient assigned the 7.5 mg dose-
Yep
later got reduced down to, one of the lower dose-
They were adjusted, yes.
They would still be evaluated in the 7.5mg
Yes.
Group.
Yes.
How, how come?
That's the way you do it. It's, it's the modified ITT or Full Analysis Set strategy, that is used for all, for all, studies. That's not nothing different from what you see in a presentation or publication on a clinical trial.
Yeah, let me just add here that in this particular study, the dose-finding phase II-B study, the key thing for us as drug developers is really to understand how does different doses correspond to different degrees of effect? This is why you always need to do this type of, we call it protocol or PS analysis, so that you really look at what does an actual dose give in terms of effect
This is really where we need to select the dose
... for phase III.
That leads nicely into the next question, 'cause that was just are the, the protocol-compliant subject set, is those generated applying the same statistical, analysis?
Yes, yes.
that you do there?
Yes.
Full Analysis.
The MMRM, the same, same statistical model.
Mm.
Everything is similar. The difference is the that the patients are divided in different into the right dose cohorts or the right, the dose cohorts they actually had, the dose they actually had
That they were compliant to the drug treatment more than 80% throughout, throughout the study.
Going into the, more of the, phase III and, and path forward here, what type of study size would be needed to replicate the phase II-B data with a decent statistical power?
I think that Nicholas is-
Yeah, we, we can go look at precedent, we can look at the statistics we with the data that we have, and the, the good thing about the phase II-B study is that actually delivered those response. We have a fair understanding of the variability in the different endpoints. That and all this taken together indicates that at least one phase III study would be of similar size that we have already done in the phase II-B. Similar number of patients, although here in that, in that, in that case, we will have less, less treatment arms, of course.
To remind the audience, we had about 150 patients in this trial, in the phase II trial.
Do we want to comment anything further, in regards to, how we are looking to run the phase III study on our own or, finding a, a partner?
As I mentioned, we will evaluate all options available to us, and at this stage, it's too early to state that we're going this direction or that direction. The important thing for us now, that is really to get to the end of phase II meeting with the FDA as quick as possible. Meanwhile, as I said, in parallel, we will of course, have these type of discussions so that we have a better understanding when we have the feedback from the FDA, how we will roll out the phase III program and how the financing will be.
Having said that, and remember from the previous question that the size of such study or studies are not so large that we couldn't do it.
I mean, we have proven that we've done it before. We have all options here, going forward.
Going back to, I suppose the timelines, people are obviously curious. Can we comment on when we plan to have the end of phase II meeting with the FDA?
I wish that I could be precise here, I am not able to be that. The reason being that there are so many uncertainties that we are not in control of. We will, of course, now work very hard to get the project transferred over to IRLAB as quick as possible. We will work together with regulatory and clinical advisors to bring together this briefing pack that I talked about. When we have the briefing pack, it is an interaction with the FDA to agree on meeting time. Of course, that depends on the time schedule at the FDA as well. We will of course, communicate as soon as we know more, but rest assured this is our high priority activity for the coming months.
Mm-hmm. We have a question here on questioning, I suppose, why Ipsen chose to not continue with the mesdopetam project. Is there a reason that we have received?
Well, as you know, we were contacted early May by Ipsen, who wanted to talk to us and discuss how can we, in the most effective way, bring this forward so that it comes to regulatory approval and out on the market. During the time we have been speaking with Ipsen, they haven't really given us a clear reason why they wanted us to come into the arrangement that we now have. However, it is very clearly stated that they do see the potential of the product. They do see the potential of the product, and I think that we can see that by them offering to support us in bringing the briefing pack for the end of phase II, meeting with the FDA together.
Secondly, I think that they have an interest in the product since we have now agreed that they will have a royalty on future sales. I, I need to comment here to say that they have also been very understanding that they don't want us to pay something until we see sales of the product, because all the resources should be put in driving the project through the development activities. What I now will say, this is my pure speculation. I have not heard this from Ipsen, but since you asked me the question, I, I think that I, I should give you my, my, my pure speculative picture.
When we've been in discussion with Ipsen, it has been a lot of things happening in the Ipsen portfolio, and whether they have had an influence on their decision, their final decision, I should say, I don't know. What do I mean with developments in the portfolio? As you may remember, by the turn of the year, Ipsen acquired Albireo, having a product for a very narrow liver and biliary disease. During the spring, they had a new approval for a much broader indication in the United States. In the end of June, Ipsen reported very good phase III data from a product that they had licensed in from Genfit. sixteenth of August, Ipsen reported approval of a product for a rare skeletal disease, launching new products and putting it together, NDAs for products with good phase III takes a lot of resources.
If this has had an implication for the decision they've taken, that can only Ipsen respond to, but it is something that I have recognized. The important thing here, that is that we've come now to a decision on way forward, so that we now see that we can move forward. As I stated, we know that Ipsen has an interest also in mesdopetam in the future.
Great. Whilst we've been talking, there's been some more question coming in on the clinical side of things and how we are thinking of shaping a phase III study. There is a question here at talking about the dose. There seem to be better effect in a higher dose.
Yes.
Is there are not alternative to include higher doses, or, are we happy with the 7.5 mg?
We, we are happy with the 7.5 mg, and there are some, there's some, some actually, hard facts around that. Those who have been with us for a while and studied and followed our communications, they know that we've done a phase I-B study in Parkinson's disease patient, a phase II-A study in Parkinson's disease patients with LIDs. In those trials, we actually explored higher doses of mesdopetam. And that those studies landed in the... Or the conclusion from those studies landed us in the decision to study 2.5, 5, and 7.5 in this trial. We don't see any further benefit at higher doses
... with mesdopetam in the previous trials. This is what we perceive as the, the, the golden spot in terms of dosing 2.5 mg to 5 mg- 7.5 mg. We were, I wouldn't say lucky, but we had, that was a good prediction. We had the best effect at 7.5 mg. Also, at these doses, we, this dose range, we also have this fantastic safety and adverse events profile of the drug.
Good. Going back or, or talking about the replicability of the results. In a phase III, the question is from an outsider perspective, post hoc data points and differences between trials are more difficult to draw strong conclusions from.
Would you say that the totality of the data in a data point that's most convincing at this stage, or?
Yeah, the totality of the data and that is going. We've consistently seen antidyskinetic effects in the phase I, I-B studies, sorry, I-B studies, the phase II-A study, and the phase II-B study. There's no question about the antidyskinetic properties of the compound. The trick here now is to choose the right endpoint structure for the phase III studies or the coming studies
We think that, following the precedent in the field would be, the right way to go.
Gunnar?
I would just fill in. I have a very strong view here, and that is very similar to what you saw in my... when I read the quotation from Professor Carl Clarke. He states his belief in the product. I have a similarly strong belief in this product. Definitely.
Good. I will close out with a question around the beyond LIDs potential
How will you prioritize Parkinson's psychosis indication now when we have all rights for mesdopetam?
Can I answer? I, I'll start, and Gunnar can, can fill in, but, but in principle, we have a very strong preclinical package describing the antipsychotic properties of mesdopetam in models of Parkinson's disease.
Mm
... Parkinson's psychosis. We do believe that there is a strong reason to study this in further, further trials. At present, we don't have any active, ongoing plans to do such studies, but they are, of course, possible to do as post-registration studies or actually in parallel with phase III. That depends on the results of the discussions we will have with the market and with the potential other types of collaborations going forward. We, but we should not forget the possibility of the tardive dyskinesia indication as well.
Mm.
That's a really, really important. It's driven by the same kind of mechanisms as we do see with LIDs in Parkinson's disease. There, I think we have, at least from the market perspective, a very, very huge, a very, very large potential
I would just fill in and say, in a small company like IRLAB, we have to make a prioritization of what we actually are running. We have taken the decision that we go with LIDs as the initial indication for mesdopetam. We have now the most data in that indication, and of course, that is where we will move into phase III. Had we been a big pharma company, and we'd seen the tremendous results with regard to safety, tolerability, and the very predictive PK, you might have had a second indication go in parallel. At the present time, we in IRLAB, we have to prioritize. We cannot afford to run more than one indication in phase III for mesdopetam, as the situation is now.
Should anything change on that side, of course, then, one can revisit that position. For the moment, we are sticking with LIDs as the initial indication.
Thank you for the questions and answers.
Okay. With this, we are ending this update on mesdopetam. I would like to thank everyone for paying attention to this update, and thanks to everyone who have submitted questions. Thank you.
Thank you very much.