IRLAB Therapeutics AB (publ) (IRLABA) Earnings Call Transcript & Summary

Good morning. This is Richard Godfrey, CEO of IRLAB. Welcome to our Investor Information Presentation. This is referring to our Phase IIb study, where we can give the highlights of our top line results, mesdopetam in Parkinson's patients suffering with levodopa-induced dyskinesia. Next slide, please. We are a public company, so I should draw your attention to our disclaimer. And now maybe I should just talk you through the proposed agenda for today's meeting. We'll have an introduction and a brief summary of the top line results. We'll then move on and talk about our study objectives, the study design and, indeed, the results themselves, the primary endpoints and the secondary endpoints. We'll also talk about the safety, adverse events and tolerability profile of mesdopetam. And then we'll conclude with some analysis, some details about when we'll present the full data set and our future outlook. This morning, I am accompanied by Nicholas Waters, our Executive Vice President and Head of R&D; Joakim Tedroff, our Chief Medical Officer; and Viktor Siewertz, our CFO. Next slide, please. Just by way of summary, this is referring to our Phase IIb study, a randomized placebo-controlled study evaluating the effect on daily ON-time without troublesome dyskinesias with mesdopetam. So before I start talking about the results, maybe just a few points of note. At this point, we will not be able to talk about numeric -- of absolute numbers, but we will be able to talk about trends and statistical interpretation of these. There will be an opportunity to ask questions in the link connected to this broadcast. So unfortunately, the primary endpoint of improved ON-time did not meet statistical significance. However, this is a Phase IIb study where our objective is to learn as much as possible about mesdopetam and how we could use it to help Parkinson's patients. We have increasing confidence that the molecule is safe. The safety and adverse event profile and the tolerability of mesdopetam was pretty much on par with placebo, giving us a great deal of confidence that this drug can be used safely with patients. However, we are very encouraged, a secondary endpoint, a very well-established and often used scale to assess dyskinesias, known as the UDysRS, demonstrated a very interesting and encouraging dyskinetic -- anti-dyskinetic effect in Parkinson's patients. Furthermore, there was no apparent impairment in motor function and a reduction in OFF-time. These were both very encouraging patterns that we saw in the data, and we believe that it gives us a lot of hope for developing this drug to help patients with dyskinesias. Furthermore, as a Phase IIb study with various doses being evaluated, we actually have got increased confidence that the optimal dose for using mesdopetam in these patients is 7.5 milligrams twice a day. Of course, going forward, we must do a complete analysis of the entire data set and have a deep consideration of the data taken on board much advice from KOLs and others regarding the possible use of mesdopetam in Parkinson's disease. Our partner, Ipsen, concurs with our analysis of the top line data. But at this moment, we cannot comment on their disposition regarding the future clinical development of mesdopetam or, indeed, the partnership. So that concludes the summary, and I'll now hand over to Nicholas and Joakim, who will talk you through the data. Thank you.

All right. I should have unmuted before. Nicholas Waters here. Thank you very much for listening in today. We have a quite interesting session ahead of us. The study, as we have discussed, is a Phase IIb study. It's a randomized, placebo-controlled, dose-response study, looking at daily ON-time as the primary endpoint in Parkinson's patients with L-dopa-induced dyskinesia. So the primary objective was to evaluate the efficacy of 3 different doses of mesdopetam versus placebo. We used the 24-hour Hauser diaries to actually assess that. That is a subjective rating by the patients delivered to physicians during the study. There are a number of secondary objectives and endpoints also, where we're looking at the effect on Parkinson's disease per se, that's using the UDysRS scale. We are looking at various aspects of Parkinsonism, that is for instance OFF-time. We're looking also at secondary efficacy endpoints in this study, also collecting information on anti-dyskinetic effects using the unified dyskinesia rating scale, the UDysRS, which is a well-established scale since a number of years back. And of course, safety and tolerability. So there are a number of aspects that we are investigating using different types of instruments in the study. Joakim, could you give a brief on the design of the study so that everybody is on board with that?

Sure. This is Joakim Tedroff, I'm Chief Medical Officer of IRLAB. Just a brief overview of the study. It was a Phase IIb study where we studied 3 doses of mesdopetam: 2.5, 5 and 7.5 milligrams given twice daily and the placebo arm for 3 months, 12 weeks. And 195 patients were screened, 156 randomized and 125 patients completed the full study period. It was conducted in a number of sites in Europe, Israel and the U.S. And in brief, patients were screened, whereafter they were trained to fill in diaries, filling in diaries after that randomization. A run-in period with 5-milligram dose for a week and then getting the randomized dose at visit 2, whereafter there were several visits at 4 weeks, 8 weeks and 12 weeks, where clinical assessments and diaries were made.

So we then continue to the results on the top line -- the top line results on the primary endpoint, and that was change in daily ON-time without troublesome dyskinesia, an endpoint we have had successes with in previous studies. In this study, we did not see statistical significance by mesdopetam over placebo as we've reported this morning or at last night, actually, for the primary endpoint. There are some interesting aspects of -- on the primary endpoint, which we will continue to work on. We'll come back to that. The study population, which we used in this trial, we have an average age of about 65 years, which is very normal for this population. They had LIDs, L-dopa-induced dyskinesias at least 2 days -- 2 hours a day to be included in the study. And otherwise, they are similar to what we've seen in other trials addressing dyskinesia. So if you look at the secondary endpoints, exploratory -- not the exploratory, sorry, key secondary and secondary endpoints in the study. As mentioned before, we had 2 ways of assessing dyskinesia or efficacy on dyskinesia. One was the primary endpoint, the Hauser diaries, 24-hour diaries, the subjective measures. And then we have the objective and subjective measures collected using UDysRS. And in the UDysRS, which assesses dyskinesia in ON-phase of the patients, we see a clear and statistically compelling effect on dyskinesia. Already at 4 weeks, we have a nominal p-value about 0.045 and that goes on through the study with a nominal significance at the end of the 12-week study of about 0.026. So it really indicates that the drug has an anti-dyskinetic effect in the ON-phases. There were a couple of other really interesting findings in the top line results. The effect on dyskinesia in the UDysRS scale was corroborated by a numerical improvement in scales also addressing disability for the patients. The patients' disability should go down if you reduce dyskinesia, and that was also corroborated by the scales that we used, UDysRS 1b and 4 and the MDS-UPDRS Part 4.2. Another really, really valuable aspect of the compound or the effects that we saw in the data is that we see a reduced OFF-time. This is a numerical effect that we see, but it's -- it has a very clear dose response pattern over the 3 doses we have studied. So -- and that is a clearly valuable effect for this patient population. Further, we also used the UPDRS Part II, traditional scale to measure effects on Parkinson's disease. And the desired outcome here is that we should have no change in that scale, and that was actually what we saw indicating that we don't have any -- mesdopetam does not impair any motor functions in this population. So -- and then looking at the adverse event profile, Joakim?

Yes. The adverse event profile was similar to placebo and the tolerability was very good. Early withdrawal from the study due to any adverse event occurred in similar proportions in the patients randomized on mesdopetam or placebo. Any reported adverse event was 56.9% in mesdopetam-treated subjects compared to 46.2% in placebo-treated subjects. The most common reported adverse events were related to the nervous system, the so-called nervous system disorder, SOC and it was reported in similar proportions in mesdopetam-treated and placebo-treated subjects. We had a particular emphasis on collecting events relating to increased Parkinsonism since we saw that in our previous Phase IIa study. But in this study, Parkinsonism was reported by 4% of mesdopetam-treated subjects and 10% of placebo-treated subjects. So in that respect, there was no increase in Parkinsonism. There was, however, a slightly higher number of subjects treated with mesdopetam who reported decreased mobility during the beginning of the treatment, but that seemed to wear off with time since we didn't see it during months 2 and 3. Seven randomized patients reported serious adverse events but they were distributed both in the mesdopetam and placebo treatment arms, and they were mostly not considered related to treatment. One assay was considered probably related to mesdopetam treatment. There were 2 deaths in the study, which were considered not related to mesdopetam treatment.

So to summarize what we think what we have seen here in this study is, of course, that we did not meet the primary endpoint. But we -- as we used 2 different scales to assess dyskinesia, we believe that we can claim that we have proven or shown that the drug has an anti-dyskinetic effect. This anti-dyskinetic effect actually is obtained without impairing normal motor function, and that is really, really important. And it's also corroborated and strengthened by the fact that we see a reduction in OFF, which seems to be dose related in the study. And this occurs at doses where we don't see any adverse events that goes beyond what we see in the placebo group. So an anti-dyskinetic effect without compromising motor function and without paying with side effects is a really interesting profile. This was a dose-finding study, which came out with our understanding that the 7.5 milligram b.i.d. dose is the preferred dose for further clinical studies.

Thank you, Nicholas. Thank you, Joakim. So I think from a personal note here, I think we've now conducted 2 Phase II studies with mesdopetam, both of which showed anti-dyskinetic effects, which I think is really very compelling. And we've learned an awful lot about the pharmacology of the compound, the safety of the compound and how to use the compound. And most certainly, I think we have a very compelling, interesting profile and very encouraging trends of efficacy. What's left now, of course, is that we must complete a full analysis of the data sets, and that will continue over the coming weeks and months. We will endeavor to make complete disclosure of all of these results in various abstracts to be published at different scientific congresses and also publications in scientific journals during the year. As you know, Ipsen holds the worldwide license for the continued development and commercialization of mesdopetam, and we continue to work closely with Ipsen to understand this data and identify a way forward. But at this moment, we cannot comment on their disposition or their decision-making regarding the future clinical development or the partnership at this time. So I think we've learnt an awful lot. Whilst we're disappointed that the top-line results were missed, we're very encouraged by the second-line data, the learnings that we have in terms of the safety profile and the dosing, and we have a lot more work to do. And next slide, please. So now I'd like to open to some questions. I will act as a moderator here as I have visibility of the questions, and I'll aim to either answer them or direct them to Nicholas and Joakim. I'll read the questions out so that we can then answer them appropriately.

So the first question reads, in the press release yesterday, you reported that the primary endpoint did not reach statistical significance. However, you did not report any numbers on this measure. Do you see any numerical trend towards the potential improvement using the patient diaries? Is there any potential reason for discrepancy with this measure compared to the IIa data you reported previously? Nicholas, would you like to respond to that?

Yes. As Richard pointed out, we are not at this time able to really dig into the numbers in detail or the quantitative aspects of the study. However, indeed, there were trends in the data which are in the right directions, but it did not reach the statistical significance as we have reported upon.

Yes. Thank you. The next question reads, you report a positive significant p-value using the UDysRS scale from week 4. Could you comment on how big the actual numerical difference is and how big the doses it was related to in order for -- and how big does it have to be for Ipsen to have confidence enough to move mesdopetam into Phase III? I can certainly advise that reference to my previous comment. We can't really comment on Ipsen's decision-making. But your question regarding the scale of the numerical values, again, I'll ask Nicholas to comment on that and the dose response.

Yes. The effect is clearly significant, and it actually goes -- the significance goes across a number of the doses. And the quantitative aspects of this, we are not at this time able to discuss, but they look interesting, very interesting.

Yes, we do. Thank you, Nicholas. The next question reads, is there a biological reason, a mechanism of action, to see how the numerical improvement of OFF-time? Again -- Nicholas, again, would you like to address that?

Joakim, would you like to respond to the [ OFF-time ]?

Well, it's -- dopamine D3 antagonists are known to, at certain doses, to increase locomotor function in animal studies. So there is, depending on the specific pharmacological mechanism of action of mesdopetam, reason to believe that it can improve OFF-time, yes.

Yes. And the next question reads, are the 2023 time lines for the other assets in development, for example, the Phase II study in pirepemat and the upcoming Phase I study is going to be maintained? And certainly, the guidance at this moment is they must definitely will. There is no reason for us to offer any justification for slowing down the progress on these other assets. And that's part of the tremendous value proposition that IRLAB has in that we are identifying completely novel compounds to address these discrete complications in Parkinson's disease. The biology is quite different, the compounds are quite different, and we will continue with those development time lines. The next question reads, could you provide some further details on the significance of the secondary UDysRS efficacy endpoint in the study? It's clearly an important metric as the FDA approved GOCOVRI for LIDs was based on 2 pivotal studies assessing the UDysRS as the primary outcome, which set an encouraging precedent. Have IRLAB or Ipsen thought about how meeting the secondary endpoint might shape the future development of the asset? So maybe Joakim, you'd like to comment on this?

As Richard alluded to, we can't comment on Ipsen's decision-making. But as the question alludes to, the UDysRS is a very important scale and has been previously used in regulatory approval for LIDs, as you mentioned, GOCOVRI. It is a scale that has the characteristics of including both patient-reported outcome and objective scoring. And with time, we can provide you in publications, et cetera, on the various components of the UDysRS that we have achieved in this study. We -- I see it as a very encouraging finding. The UDysRS is suggested by the regulatory authorities to be an important rating scale for levodopa-induced dyskinesias.

Yes. Thank you. The next question in a similar line says that, is there any possibility that IRLAB could conduct independent studies with mesdopetam? And again, as we alluded to at the beginning, Ipsen holds the worldwide rights for continued development and commercialization. Full evaluation of the data needs to be undertaken, and we can't really comment on any decisions regarding that. But we are very encouraged by this UDysRS readout. And I think that needs to be fully understood before further development can be concluded. And we just go to the next question. We're getting more questions coming in. Do the results in any way affect pirepemat? No, I don't think they do. Can you discuss the statistical correlation between patient diary endpoints and the UDysRS? Again, Nicholas, Viktor, would you like to comment on that?

Yes, I can comment on that. The relationships between the scales have not been available to us in the top-line results. That is something that we will, of course, evaluate during the full analysis of the data.

Yes. Another question. Will you likely need to do at least 2 Phase IIb or III studies from now given the mixed results in this study? And again, I think we really can't comment on the future development. There's still a lot more work to be done. So we can't really comment on that. And there's a question for you, to talk to Nicholas. Can you comment on the higher p-value in week 12 relative to week 8 in the UDysRS scale, seems more variability?

One shouldn't use the p-value as an assessment of the effects, the size or the magnitude. Here, we have -- we are dealing with variabilities and we are dealing with, as you saw, patients dropping out during the trial. We randomized 155, and 125 came out. So during the course of the study, of course, less and less patients are available for each treatment arm, which changes the statistics a little bit over time. But the general impression that we provided in the press release and today's talk is that there is a clear signal on -- as an anti-dyskinetic for mesdopetam.

Yes. The next question reads, I think it's a good question, could you give some details on the SAEs that could be related to mesdopetam?

Yes. I mean, the -- it was just one assay that by investigator was considered to be probably related to mesdopetam, and that was a patient who fell probably due to poor gait. And this is something that happens with patients all the time. And the assessment at that time was that it was related to mesdopetam. But I must bear in mind that we have no reasons given the overall data to believe that mesdopetam does anything to reduce mobility, gait function, et cetera. So that's the only thing I can comment. In all these trials, when you have very elderly, neurologically severely ill patients, things happen all the time, unfortunately.

Yes. The next question is linked to that, I think. The safety data suggests that even a higher dose could potentially be used. Do you have any thoughts on that? Nicholas and Joakim, maybe?

Well, we have studied higher doses in previous Phase Ib in Phase IIa studies. And to us, this -- the choice of doses for this trial was based on the previous understanding of the drug. And we do believe that the optimal dose would be the 7.5 b.i.d. dose.