IRLAB Therapeutics AB

STO:IRLAB A

Earnings Call Analysis

Earnings Call Transcript 2023-Q2

[Tove Bergenholt, executive]

[Audio Gap]Third quarter have passed and IRLAB Therapeutics have reported for the second quarter in 2023. In this live broadcast, viewers can ask their questions in the live chat. So to present the second quarter, I'm happy to present to you CEO, Gunnar Olsson; EVP and Head of R&D, Mr. Nicholas Waters; and CFO, Viktor Siewertz.So please, go ahead.

[Gunnar Olsson, executive]

Thank you. Good morning and welcome to this quarterly update. The agenda for today is that I will give you news from the period. This will be followed by Nicholas to give us an R&D update. Then Viktor will follow to give us an update on the financials. We will then conclude and open up the question-and-answer session.Operational highlights during the second quarter. For mesdopetam, in May a discussion was initiated between Ipsen and IRLAB to outline what would be the best way forward to take mesdopetam to registration so that it could be available for patients with Parkinson's disease. For 757 and 942: in May, IRLAB and McQuade Center for Strategic Research and Development, we made an agreement that gives MSRD the rights to evaluate 2 of IRLAB's projects; the neuropsychiatric programs for 757 and 942. The purpose here that is to investigate if there is a possibility to come to a collaboration agreement to develop the compounds from where they are now up to clinical proof of concept. Pirepemat: at the end of May, IRLAB announced that all of the 38 clinics in the study were up and running and are now recruiting patients into the pirepemat Phase IIb study.With regard to ISP: in mid-June IRLAB presented at the IBAGS conference in Stockholm around the ISP. We shared new information about the usefulness and the uniqueness of our ISP platform for drug discovery purposes. AGM: June 20, we had the annual AGM and at this AGM, the Board was extended with 3 new members; Veronica Wallin, Chris Nordstedt and Daniel Johnsson, Investor meetings: we presented at several national investor conferences arranged by ABG and Redeye and we've had ongoing discussions with both national and international investors to provide updates on the company. Things that have happened after the period. For pirepemat, in mid-July the independent safety and data monitoring board had their first preplanned review of data. This review was triggered by the first 25 patients that had gone through all bits of the study. The DSMB unanimously recommended the company to continue the study according to the present study protocol.For ISP: we participated in an international competition focusing on how to apply machine learning to describe animal behavior, something that is very important to us since our preclinical experiments are built on animal experimentation to see effect on animal behavior. The competition was arranged by a consortium of neuroscientists from the Northwestern and Caltech universities. IRLAB was awarded the second place in this competition and I think that this very well demonstrates the very high sophistication and the frontline position we have in using machine learning in our discovery and development activities. The proceedings from this competition has been published. As you see on the slide, there is the link to the publication.For mesdopetam: on August 21, IRLAB secured the ownership and all rights to the Phase III-ready mesdopetam project and that means that IRLAB is now in control of further clinical development as well as commercialization of the product. On the 22nd of August, IRLAB gave an update of the mesdopetam project and that included additional data from the Phase IIb study in LIDs and it also included data from the 3 Phase I studies performed by Ipsen. All in all the data show that mesdopetam has shown anti-dyskinetic efficacy, it has an anti-parkinsonian effect without compromising normal motor function and it has a safety and tolerability profile that was on par with placebo. And that means that our judgment is that now mesdopetam, we need to prepare for an end of Phase II meeting with the FDA in order to define the Phase III program. On August 28, results from the Phase IIb study with mesdopetam was presented at the MDS Congress in Copenhagen.Financial highlights for the quarter. Net revenue, almost SEK 7 million. Total operating expenses, almost SEK 52 million. Operating results, minus SEK 45 million. Cash flow, minus SEK 53 million. Cash at the end of the period, SEK 156 million. Total number of registered shares close to 52 million, the same number as at the last quarterly update. So IRLAB having now a world-leading portfolio of compounds to improve Parkinson's treatment. We are building on pioneering biology and knowledge stemming from the research team around the Nobel laureate, Arvid Carlsson. From that, the development of the ISP, the platform to generate new candidate drug molecules. We have a focused strategy based on the deep knowledge about Parkinson's biology. We have validated business model based on clinical proof of concept. So we have taken molecules from discovery up to Phase I, Phase II and now being Phase III-ready and we have had deal-making experience.We have a broad and solid portfolio where all the different stages of the Parkinson's disease are addressed and every molecule having the potential to be a blockbuster. We have an organization positioned for success. So now a little bit about Parkinson's to set the scene how we see the disease and how our molecules fit in. So what happens when you get Parkinson's disease. Well, it is when more than 50% of your cells in the brain producing dopamine has died off. Why is this so important? Well, dopamine is one of the absolutely most important signaling substances engaged in a number of different functionalities of the brain. Why does it happen? In a small proportion, it is of genetical background and in the most or if I say in the majority of cases, it is environmental factors. Hallmark symptoms, the characteristics: there is the tremor, it is the bradykinesia with slow movements and it is rigidity. If you try to bend an arm, it will be very rigid.There are other symptoms and maybe 1 of the most important one being posture instability. But the key take home message that is Parkinson's disease is a chronic one and it is progressive and that means that this is lifelong and it worsens over time. What are the key problems for the individual patient? Well, different surveys have approached patients to ask what is it that is bothering you? And here is one of the largest surveys. And as I said, the most frequent bothersome symptoms that is balance and instability leading to foods; the hallmark symptoms of tremor, rigidity, bradykinesia; impairment of cognition; and mood changes like apathy, anxiety and others. And the important thing here is that our projects, they align with these areas and we can see that on this slide.If we look to the right, you see the impaired balance and falls, pirepemat; hallmark symptoms, our 1117; cognitive decline, pirepemat and 942; mood changes, mesdopetam, 757, 942; and the motor complications seen with chronic levodopa treatment, mesdopetam. To the left, you see estimation of about 6 million diagnosed patients in the major markets and you see that in the next 15 to 20 years this will be more than doubled. So it is a growing medical unmet need. Here is just to illustrate the ISP, the unique platform for identifying new drugs. We're using a computer-based advanced systems biology technology to discover the new molecules. And if you look at the right, you see a 3-dimensional picture rotating and every dot is a molecule and then on the different axis, we could apply different characterizations of things we want to see with the molecule. This is just for simplicity.In our computer modeling, we are simulating with up to 600, 700 dimensions to really see that a molecule brings what we want it to bring. And all in all, this results in first-in-class medicines because it's really innovation and that in turn generates very strong IP position. The important thing for us is that already at the time when we select a new molecule, we see where we have the largest potential. We are guided on where to go. Maybe the most important thing that is that this gives higher probability of success to reach late clinical development when we compare to industry standard, which is using the target generated strategy for screening. So this is our engine of creating our innovative molecules. With the ISP, we have built this portfolio and as said in my view, this is the world-leading portfolio. Mesdopetam, our lead almost advanced project, now have finalized the Phase IIb study and the next major event that is a end of Phase II meeting with the FDA to outline a Phase III program for treatment of LIDs.Pirepemat, our compound to prevent falls in Parkinson's disease. We are now running the Phase IIb study and we hope to see the results coming out first half next year. 757, our drug for apathy. We are now working in the preclinical field and we hope to have the project Phase I ready by the end of the year. The 942, our treatment for cognitive impairment preclinical development, we hope to see this one being Phase I ready by first half next year. And 1117, our treatment for the hallmark symptoms, but without all the complications we see with chronic levodopa treatment. We hope to see this one being phase ready during next year. And a product with the profile that we see for 1117, it has actually the potential to replace levodopa in the future. Something about now how Parkinson's disease evolves over the lifetime of the patient and how our products fit.Here you see a graphical slide of how the development of Parkinson's disease. At time point 0 at the middle of the contour, that's when the symptoms occur and the diagnosis is defined. Then you see over time increasing symptoms and where we are focusing that is on the psychiatric symptoms and the motor symptoms. And how do the projects fit? Talking about mesdopetam. You see here in gray boxes where we see that mesdopetam will provide some benefit. We then go to pirepemat, we see other gray boxes filling up and this is where pirepemat will be able to help. Then 757 yet another box, 942 and the 1117. And then the important thing that is to see what is the picture looking like when we take them all together. As you see, with the portfolio that we have and that we're working with presently, we will be able to provide beneficial effects to patients throughout their journey of the disease in the great majority of symptoms and complications and that makes us excited about our portfolio.So with this, I think it's time to now leave over to Nicholas, who will give you some more detailed update on the R&D side. So please, Nicholas.

[Nicholas Waters, executive]

Thank you, Gunnar. And thank you, everyone, out there for listening in today. I will rapidly continue with some updates on mesdopetam that we have seen in the past quarter and during the summer. Mesdopetam is a totally novel molecule with a novel mechanism of action. As Gunnar mentioned, this is a first-in-class product. It has potential in treating motor complications in Parkinson's disease such as LIDs, but also previously we have published data indicating that we also perhaps can prevent the occurrence of levodopa-induced dyskinesias. It has potential in psychosis and also in other indications. During the development of mesdopetam, we have now created a quite large body of evidence which supports the novel treatment for dyskinesia in PD and this started many years ago; I wouldn't say many, but some years ago with Phase I studies.We added then a Phase Ib study in Parkinson's patients where we looked at safety, tolerability, but also at efficacy. Gained efficacy signals in that study plus increased understanding of the pharmacokinetic properties in the population. Then we run a larger Phase IIa study; also safety, tolerability, but efficacy was measured using different instruments. And throughout these initial studies we learned a lot about the usefulness of the different scales, the usefulness of mesdopetam as a treatment in this population. We decided to start a Phase IIb study, which has now been concluded and we presented some data earlier last week and also at Movement Disorder Society meeting in Copenhagen on Monday. And with this package, we believe that we now have sufficient documentation around the safety, tolerability, but also estimations of efficacy on the compound so that we can move towards pivotal studies.That of course means that we prefer to have a end of Phase II discussion with the FDA before we enter into that program. It's fair to also mention that there are other indications possible for mesdopetam. Having a drug with the profile that we've seen in this quite severe neurological population of Parkinson's patients, it's clear that expansion into other types of indications is possible and of course PD psychosis is one lifecycle management option. We also have LIDs prevention, which is an interesting and challenging prospect in terms of clinical trials. But then we also have tardive dyskinesia, which is to some extent driven by the same mechanisms as LIDs. So therefore, we believe there is a fit for mesdopetam in that indication as well.One thing that's important to mention here is that during the collaboration with Ipsen in the past 2 years, they have been extremely diligent in pursuing certain aspects of the development of mesdopetam and these are studies which are necessary to have when you file for a Phase III application. And these are Phase I studies looking at primarily the pharmacokinetics of a compound and that means the absorption, the distribution and excretion of the compound and one does so in different genetic populations such as Asians, non-Asians, African Americans, et cetera. And then we've looked at the possibility of mesdopetam interacting with other drugs and changing the profile of mesdopetam or the other drug actually and there we see no risks. And then a mass balance, that's a study where you look at where all of the compound goes and how long it takes before it leaves the body as in total.The implication of these results are really important for the further development of the compound. We have predictable pharmacokinetics. There is no difference between the different populations we've studied. The genetics have no impact on the -- different genetics have no impact or very little impact on the pharmacokinetic profile. We expect that we will have a simple and uniform dosing, 1 pill twice daily that will help the patients so there is low risk of dosing errors. There is no complicated dosing strategies for this. There will be no complicated dosing strategies with mesdopetam. And the data above all that enables use in a larger and genetically diverse population. So now we do not have to have restrictions in the inclusion criteria in further studies or on the market depending on -- based on the data that we generated so far. And that's a really, really important part of development to establish such data.Jumping directly into the end of the Phase IIb study. We presented top line results in January and since then we've been working with the analysis. We presented now last week further information on the results of the study and also on a poster presented at Movement Disorder Society, which is referenced here. And for you out there, you can find the poster on our web page under the publication page. What we discovered and here's just a snapshot of the data I'll have to say that. What we found and our conclusions from the study is that we have consistent dose response and, what is very important, clinically meaningful anti-dyskinetic efficacy. And this is something we've seen in Phase Ib, Phase IIa and now also in Phase IIb, clinically meaningful anti-dyskinetic efficacy and that is measured by different scales.And in our case we see a very profound effect on the unified dyskinesia rating scale, which is the preferred scale with regulators in terms of primary endpoints, et cetera, in studies like this and then we see improvement in good arm time. In addition, we saw a quite significant dose dependent reduction in OFF-time in this study as well. which is an important add-on to the profile of mesdopetam. This is a typical effect with anti-parkinsonian drugs. We don't see any side effects which differ from placebo. We don't have any safety aspects which differ from placebo. So we can achieve a full anti-dyskinetic effect according to the dose response we have established without compromising motor function or adding any problems for the patients.Predictable plasma exposure as I said, linear and dose dependent and then we have also managed to now select a dose for further investigation in pivotal trials and that is we have basically ticked off all the important aspects to move to the next level of development. So next step will be an end of Phase II meeting with the FDA and that means that we need to build a briefing book to provide the FDA or any other regulator around the world by the way. And that we will do in collaboration with experienced regulatory and clinical advisers, people that have done this many times before with the specific objective of Parkinson's treatments. We will have support from Ipsen as stated in the press releases we've provided during the peak period and this is all to define the final protocol for a Phase III program. Another aspect of the work that we need to do now is to capitalize on the results to ensure the financing for the Phase III program.Going forward to pirepemat I should say. This is also a first-in-class molecule and this is in development now to improve balance and reduce the risk of falls in Parkinson's disease. Falls is one of the biggest problems, as also Gunnar mentioned. Looking at the polls out there, this is one of the biggest problems that the patients themselves report, the balance and the falls complications. And about 50% of all Parkinson's patients falls recurrently globally. The cost of a fall is quite significant, around $30,000 according to U.S. costs and there is no available treatment at present. So this is a large unmet need. With pirepemat, we started the Phase IIb study last year early in quarter 1 and, as Gunnar mentioned, we have now all centers ongoing recruiting across Europe in this trial. We expect or plan to have all the patients enrolled by the end of the year and to have data to present during the spring of next year or H1.As I said, this is a first-in-class molecule as well. It is a novel mechanism to activate certain circuitries in the cortex of the brain. It has a quite substantial potential in terms of both commercial and treatment. Going to the regulatory side, we have achieved regulatory approval for the Phase IIb study across 6 countries in Europe. We have been advised by the FDA to front load our development plan with a number of studies, which we've now done and they have been successfully completed. And as for mesdopetam, pirepemat has also been given a unique stem name by WHO indicating this represents a new class of treatment. Also here we have now building on the comprehensive package to move forward to further trials. The Phase I single ascending, multiple ascending doses in healthy volunteers looking at PK safety and tolerability.We went on to tablet formulation, then did a Phase IIa study where we looked at safety and tolerability in the intended population. These are elderly patients with cognitive impairment and Parkinson's disease. This is the population that falls. And we could extract information from that trial indicating cognitive improvement, improvement in balance, promises of reduced falls. And now we're running a trial focusing on exactly those aspects. We're looking at falls, we're looking at balance, we're looking at certain neuropsychiatric endpoints as well. And it's a 3-arm trial equally distributed across 2 doses of pirepemat and placebo; 3-month treatment period, a dose de-escalation period and then a follow-up up to 1 month of the patients. And as Gunnar mentioned, during the summer the first 25 patients had gone through all of this and we are now continuing building on further patients, recruiting further patients into the trial.A brief note on the preclinical program; 757, 942 and 1117. 757 to treat apathy, which is today an untreated indication or symptom in many neurological disorders. This goes beyond Parkinson's disease. And then 942 to restore cognitive function, this is a drug which in preclinical studies have showed excellent efficacy in reversing cognitive dysfunctions. And then 1117, which is what we believe could be a really, really interesting prospect moving forward. It's a once-daily treatment for Parkinson's and that's something that is not out there today to treat the hallmark symptoms without inducing all of the complications we see today with today's levodopa treatment. And we boldly say that this could be a next-generation treatment for Parkinson's disease. Also mentioned previously, 757 and 942 is now being evaluated in a partly collaboration with MSRD/Otsuka. They're looking at the documentation we have generated so far and we're looking into the possibilities of building a collaboration for both of these assets.When it comes to the indication as such, this is quite huge. There is about 10 million Americans with apathy and 10 million Europeans at the same time affected by apathy and in neurological disorders, this occurs at very high frequency. This is a very well-known comorbidity, but there is no really good treatment. There are a number of hypotheses on the genesis of apathy and we are targeting on 1 of those, which deals with the crosstalk between different brain areas, which is hampered in people with apathy, and we can strengthen or reverse that or improve that crosstalk with 757. And then cognitive dysfunction is quite well known in the public domain. More often one thinks about Alzheimer's disease and cognitive dysfunctions, but Parkinson's also is a disease with a lot of cognitive issues during the course or the development of disorder and in general, about 12% to 15% of all people over 65 suffer cognitive impairments.And as I said before, 942 has a very, very clear cognitive enhancing profile across different cognitive modalities as they are called in preclinical studies. And now we're bringing both of these molecules towards Phase I. 757 will be Phase I ready at the end of the year, 942 during next year and this is according to our plans and what we've communicated before. And lastly, but not least, 1117; the next-generation treatment for Parkinson's disease. This can be used as a monotherapy as well as an add-on to levodopa we believe. It has the potential to be an effective treatment without the complications we see with levodopa. This was a drug that we nominated early this year and we are now doing the preclinical exploration and development activities hoping to reach a Phase I ready state during next calendar year.I will now turn over to Viktor to give a brief update on the finances. Viktor?

[Viktor Siewertz, executive]

Thank you, Nicholas. Finances: most important figure is of course the cash position, which was about SEK 156 million at the end of Q2. There is a continued focus on cost control. The costs were about the same level as in Q1 and also the same level as in Q2 last year if you adjust for the cost in Q1 for the former CEO. We do expect the cost to go down a little bit towards the end of the year as important activities are closing in on being finalized. During the quarter and also during the rest of the year, we will continue investing in the Phase IIb study with pirepemat of course and we will also continue to invest in the preclinical development of the preclinical projects; 757, 942 and 1117. As you can see in the rightmost graph at the bottom, the number of employees has been stable for more than a year showing that the operations is basically ongoing at a steady pace. The analysts that cover us and are with us today is Fredrik at Redeye, Gonzalo at ABG and Soo at Edison. And we hope to get some good questions from them after the presentation.So over to you, Gunnar, to conclude.

[Gunnar Olsson, executive]

Yes. Capitulation, this is the portfolio. We have talked about this so I proceed. Some words about anticipated key development milestones over the next year. Q3, actually what you see here to the left, we have already mentioned what happened after the period so I won't repeat that. But when we look into Q4, we anticipate a second DSMB review of the Phase II study with pirepemat and that is again according to a preplanned model that we have. We also anticipate that the pirepemat Phase IIb study will come to end of patient recruitment by the end of the year. As we mentioned, 757 we hope to see a Phase I ready project at year-end. We are planning for a Capital Markets Day in Q4 and we will participate at investor events with ABG, with Pareto, Redeye, BioStock and SEB. We will also participate in scientific congresses.For first half next year: we estimate to see pirepemat Phase IIb top line results, we estimate to see 942 coming to Phase I readiness and we will continue the 1117 preparation aiming for Phase I. You see here at the bottom without any time location so to say, there is that end of Phase II meeting with the FDA for mesdopetam. That is a very high priority for us. But since we are not the one setting the date for such a meeting, we need to interact with the FDA. We just put it here as an event without confirmed time frame. Of course when we know more, we will communicate. So IRLAB, a world-leading portfolio based on pioneering biology and a unique platform for drug discovery and the ISP, focused strategy on Parkinson's based on the profound understanding of Parkinson's biology, validated business model built on clinical proof-of-concept, broad and solid portfolio as you have seen and an organization positioned for success.That's the end of the formal presentation and I think that we are now moving over to the Q&A session. So if I invite Nicholas and Viktor to the table as well.

[Tove Bergenholt, executive]

Thank you so much, Gunnar, Nicholas and Viktor for that presentation. We will soon hand over to some equity analysts. But first off, let me ask you, could you please take us through the events that led from Ipsen being your partner to where you are today?

[Gunnar Olsson, executive]

It actually started with a phone call to me on the 1st of May from Ipsen. It was clearly stated that we would like to discuss how we the best way could take the product forward so that we can reach registration and getting a product. We have had then long discussions with Ipsen. Ipsen has clearly stated that they see that this molecule has the potential to be a product and they want to see it come to the market. In parallel, we have understood that there have been ongoing activities in their own portfolio. But all in all, this led to an agreement that we closed on the 21st of August where it's very clear that Ipsen is interested in the product. They will support us in bringing together the briefing book for the end of Phase II meeting with the FDA. They will provide us with the study medication for the Phase III study.And they have been very clear that they don't want us to give any payment to them during the course of development activities because all the funding should really be to move the product forward, but they are interested in getting part of the success of the product in terms of royalties on sales. But it's good for us that the payment won't kick in until we are on the market. Then what I'm now going to say is only my pure speculation. But being in the discussion with Ipsen, of course I followed or we have followed what's happening within their company as well. It has been interesting to see that they have had some significant development in their own portfolio. So in mid-June, they had an extended approval for a product that they acquired by acquiring Albireo by turn of the year so it now has a much broader indication and use.Secondly, by end of June they reported that a project that they have in-licensed from Genfit had very positive Phase III data. And then mid-August, they reported that they had approval of a new product in the United States. All of these projects are of course closer to the market compared to mesdopetam and I don't know if it has had any impact. But I know that having these type of successes in your portfolio, you really need to invest to bring them to success and if this has had an impact on how the agreement was defined in the written agreement, we don't know. But definitely, we have a clear indication that Ipsen do have an interest in mesdopetam even if we now secure the full ownership of the compound.

[Tove Bergenholt, executive]

So now let's move on to the equity analysts and we will start off with Fredrik Thor at Redeye.

[Fredrik Thor, analyst]

I know it's very early, but I was wondering do you have any insights on how you could improve [ reportability ] of the results in a Phase III trial and especially in the good arm endpoint, maybe draw some learnings in the PS group versus the FAS group for example?

[Nicholas Waters, executive]

Of course. As I illustrated in the progression of development of mesdopetam, we've learned a lot over the past few years what to do and what not to do and we also have learned how to manage the sites and instruct doctors and patients to a much higher position now than before. So with all the knowledge we have gained over the past few years, we are quite confident that we can design and conduct further trials which will deliver what we hope they can.

[Fredrik Thor, analyst]

And in the FAS group when looking at the UDysRS scale, those tendency was less obvious than in the PS group. Is there a good explanation for that or could it just be out of randomness or do you have any sense?

[Nicholas Waters, executive]

Variability and that's just why you do all these additional analysis on a trial data set to be able to actually define the actual or the most likely effect of a drug. And the dose response we see here, I reiterate it. We've seen that also in the Phase IIa study, dose responses on the important end points indicating that we actually have a very clear understanding of the optimal dose to be used in further trials.

[Gunnar Olsson, executive]

If I just add here. In different phases of drug development, you put different type of emphasis on which analysis provides you with the best answer. In the dose finding, the most important part that is really to say what does an actual dose give in terms of effects both on the effect side as well as on the safety side. This is why this type of, we call it PS, protocol analysis is so important in this stage of development. In Phase III, that is a different thing. Then you really need to show you have an effect when you have selected the dose that you're testing and then you're always to the intention to treat analysis that is the FAS analysis that we showed, which then you really need to document that giving a treatment according to certain schedule, it will deliver what you wanted to see. But going back to the Phase IIb study, the way it was designed so that there was the possibility of dose adjusting early in the study. It was very important for us to really say what was the dicta when we looked to treatment effects according to the actual dose that the patient had for the majority of time in the study.

[Fredrik Thor, analyst]

So basically the dose dependency is most important in the PS population is the takeaway I guess in this stage?

[Nicholas Waters, executive]

Yes, because that's based on the actual dose they took.

[Fredrik Thor, analyst]

And a final question. If you were to conduct a Phase III trial in-house, how could potential commercialization look like? Would you need a distribution partner or like a licensing agreement in the NDA stage? What are the alternatives?

[Gunnar Olsson, executive]

Of course if we were to run a Phase III study, we can't today say what would it be because we need to have the end of Phase II meeting with the FDA. But what we could foresee that is that a Phase III study to repeat the findings we see in the Phase IIb study would be of the same size so roughly 150 patients per study. Of course we need to confirm that in the FDA discussion. But if that is so, then definitely it would be something that IRLAB could do on its own. Then coming to the commercialization, we don't have a commercialization organization so the most likely scenario would be that we would need to have an agreement with someone with commercial muscle to really introduce the product to the market. But again early days today, we can't give you more than speculation at this time. As we said, it's 1 week since we secured the product and got back the control of development and commercialization. We have some homework to do to really define exactly answers to the questions you have. But we are very pleased to have now a Phase III ready product in the portfolio that we have full control of and it has strengthened our position.

[Fredrik Thor, analyst]

Just a confirmation on what you said, Gunnar, about the 150 patients. Is your hope that you could have the 1 trial preapproval or 2 or has it changed since then?

[Nicholas Waters, executive]

That's a matter of discussion with regulators across the globe and first of all and first and foremost the FDA. There is precedent in these types of indications that you can bring Phase IIb, Phase IIa study as support for 1 pivotal trial. But this is an open question, we don't have the answer to that. Otherwise one does the 2 trial strategy and then also one is to hedge for the safety population, which is about 100 treatment years that needs to be added to the study.

[Gunnar Olsson, executive]

Could I just add here? One aspect that I think is important when we talk about would it be possible for a small company like IRLAB to run a Phase III and as I stated, yes, I believe so. And 1 important thing is not just the sample size, we're talking about an efficacy trial of about 150 patients. What is even more important that is that we're here talking about a treatment period of 3 months as we estimate and this should be compared to the Alzheimer trials that we've seen over the last year being in the range of 2 to 3 years in 1,500, 2,000 patients per study. So it is a very different situation that we are facing and this is why we state we believe that it could actually be realistic to run Phase III also from a small company in this indication.

[Tove Bergenholt, executive]

It's time to move on and next up is Soo Romanoff from Edison.

[Soo Romanoff, analyst]

It was good to hear the details on mesdopetam. You have a lot going on and you've made good progress on your Phase IIb trial for pirepemat for balance and avoiding falls and it was great to hear the confirmation of the timing for recruitment and the top line results in the first half. In your opinion, what would you constitute a clinically meaningful result?

[Nicholas Waters, executive]

That's something we've discussed before and it's an interesting question, Soo. If one goes to the literature, about 25% reduction in the fall rate is perceived as a clinically meaningful effect. If we go back to our own calculations from the Phase IIa study, we see that we can actually exceed that or we hope we can exceed that, but the data there supports a larger effect. But somewhere around, let's say, between 20% and 40% improvement would be really, really a huge leap forward in the possible treatment of this problem for Parkinson's patients.

[Gunnar Olsson, executive]

We should wish not forget that at present there is no treatment available to reduce even a fraction of the risk of falls. So any improvement here would be of clinical relevance.

[Soo Romanoff, analyst]

That makes sense. I'm always interested to hear about your ISP research platform and I'm looking forward to hearing more future milestones. But do we anticipate any new candidates entering Phase I for the clinical trial in the near term?

[Nicholas Waters, executive]

Yes. As we presented today, we will have 757 Phase I ready by the end of the year, which means that the next step there would be clinical trials first of all in healthy volunteers and later on in patients. Same with 942, during next year we will have it ready for Phase I as well. And perhaps also even 1117. And that would in 2025, we would have a company here with 2 late-stage programs; 1 in Phase III perhaps and even 1 approaching Phase III and then a number of Phase I assets moving towards Phase II. So we have quite hefty work ahead of us, but that's also good for all our stakeholders.

[Soo Romanoff, analyst]

It's good to hear about those and that was kind of my next question on the MSRD. Do we have any -- is there any other updates you can give us on those discussions? I mean that's obviously a huge positive and kind of kudos to you guys on the ISP.

[Gunnar Olsson, executive]

The only thing I can add here to what we've already presented that is that we are in this period where they are evaluating our compounds. Of course we are continuing developing activities with the compound to drive them forward. We see that this is something that we are hoping to come through. But of course we are at such an early stage where still the molecules are evaluated by the other side and we're waiting to see their feedback where the discussions can continue. Any development in the discussions is of course something that we will actively communicate. But the good thing is that we are in these discussions now and we'll see where they land.

[Nicholas Waters, executive]

And an important addition is that it's not only 1 way evaluation. We have a reciprocal evaluation and looking at how would a collaboration look from our perspective to be good enough for entering into such a collaboration. So there are lots of things going on, which we cannot of course discuss. But when we have some -- reach some milestones in these discussions, we will of course provide that information, we're obliged to.

[Tove Bergenholt, executive]

And last, but not least, we have Gonzalo Artiach from ABG Sundal Collier.

[Gonzalo Artiach Castañón, analyst]

I will start with 1 on the data you just presented on the 28 at the MDS Congress. If we focus there in the baseline characteristics of the treated population with mesdopetam that you presented there, it seems that the group that received the highest dose of mesdopetam also received a higher dose on average of levodopa, 32% higher versus placebo to be more exact. Why do you have this difference in levodopa dosing across groups and what are the implications, if any, of this difference on the positive signal that you have seen in this group?

[Nicholas Waters, executive]

The way we see it is very little. This is not an important difference between the groups. It's by chance of course that they end up with these perhaps differences to doses. But this is also individualized treatment with levodopa. Individualized dosing for all of the patients, but stable during the trial and it just happened to come out like that. So that has nothing really -- we don't see that as influencing the results at this stage.

[Gonzalo Artiach Castañón, analyst]

Okay. And the second one also in the same data set presented, it's regarding the primary endpoint of the study. The improvement of 1.75 hours. It seems to come from a post hoc analysis of the data scale to 16 hours awake. Could you give us a bit more color on this measure and has it ever been used in that way of the 16 hours adjustment as a primary endpoint in any previous Phase III study?

[Nicholas Waters, executive]

As we move along, we will likely not use the diaries as the tool for the primary end point as pointed out before. Now since UDysRS is the preferred endpoint for regulators, that's probably or most likely the way we will go. And also given the fantastic results we have in the Phase IIa study, the result on UDysRS in the Phase IIa study is on par or better with what has been published with other treatments before in the registration files. So therefore, that's a quite likely way forward for us. The normalization to 16-hour wake time is something that we were advised that the FDA does with the data. When they get the data set, they do that calculation to control for variability in sleeping time or patient individual sleeping time so that you compare apples with apples so to speak instead of apples with pears. So that's something that they do and we wanted to do that to be sure that we don't miss anything out. And then when you say post hoc here, that has to do with the compliance in the patient population. We wanted to look at the patients that actually took their medicines more than 80% of the time during the trial and that was done at that stage.

[Gonzalo Artiach Castañón, analyst]

Okay, great. And one last question from my side, it's from the report today. You mentioned that the pirepemat trial is recruiting slightly slower than expected and that there are actions being taken right now to speed up the recruitment. Could you give us some color on these measures that you're implementing now?

[Nicholas Waters, executive]

The measures we've been implementing during the summer and the spring actually is adding 1 country, the Netherlands; opening up 2 sites in the Netherlands quite large sites and there we have the world's experts in falls in Parkinson's as well. And then we are taking measures at every site and I can't go into the details because they would be too complicated to explain, but details on how we incentivize the patients and the doctors to actually get into the trial.

[Tove Bergenholt, executive]

And the hour's gone fast. Thank you so much for presenting. Thank you for viewing and welcome back the next time.

[Gunnar Olsson, executive]

Thank you.

[Nicholas Waters, executive]

Thank you very much.