Idorsia Ltd (IDIA) Earnings Call Transcript & Summary

Good morning, good afternoon, ladies and gentlemen, and welcome to the Idorsia call on Phase III clinical data. [Operator Instructions] Now I'd like to hand the conference over to Andrew Weiss, Head, Investor Relations and Corporate Communications. Please go ahead.

Thank you, operator. Good afternoon, and good morning to you all. This is Andrew Weiss, and I welcome everybody to our call devoted to the exciting initial data from the first pivotal study and in our Phase III program with daridorexant in patients suffering of insomnia. Today, we are here to talk you through what we've seen and share our excitement of our first impressions on daridorexant. However, I do need to remind everybody that this is a specific call on daridorexant Phase III study, hence, please keep your questions at the end of the call in this context. With me on the call are our CEO, Jean-Paul Clozel; our Chief Scientific Officer, Martine Clozel; and our Head -- our Global Head of Clinical Development, Guy Braunstein. They're here to give additional color on the results published this morning at 7:00 a.m. In these difficult times of COVID-19 isolation, we're all joining in from different locations, so we'll keep our fingers crossed that the home networks and technology that served us up to now will continue to serve us. Next slide, please. Before handing over the microphone, I need to remind everybody that we will be making forward-looking statements. You have, therefore, been appropriately warned about the risks and opportunities of investing in Idorsia shares. With that, I hand over to Jean-Paul for his introductory remarks. Jean-Paul, please.

Thank you, Andrew. And as you mentioned, in this COVID time, I hope that all of you listening are in good health. And I can tell you that at Idorsia, we are all very, very happy but we are still thinking of the very difficult situation for many patients, for many practitioners. And really, I would like to take this opportunity and to start by really thanking all the people at Idorsia but also in the hospital, in the sleep centers and all the patients who have helped us to really get to this data at the time of consignment, and it has been a really incredible effort to get to this data. Guy will show you the top line results of the study, and you will see that the data are really very important. They are scientifically very important. And therefore, we need to present the key results for scientific publications. You will see that Idorsia has discovered -- the team at Idorsia has discovered and developed a drug which can, in insomniac patients, make the patients sleep faster, sleep longer and, this is really unique, function better the next day. When I saw the results on Friday evening, I was really stunned. It's surprising because I knew we had designed a very good drug and that we had very good results in Phase II. But never in 30 years of drug discovery and development, I have seen so consistent, meaningful and clear data. It did not come by chance. Martine, who started this project in 1998, will tell you how this drug was discovered, but also the design and the execution of the clinical program had been key for the success. This is a turning point for Idorsia. Now with this data, I know that with daridorexant, Idorsia can become a fully-fledged biopharmaceutical company. And now I can -- the next slide, and I can hand over to Martine.

Good afternoon, good morning. In a few minutes, you will see the top line results, which Guy will present to you. And you will see why I think we are at the birth of a revolution for patients with insomnia. Our journey started when I invited Masashi Yanagisawa who, for 10 years, has been my friendly competitor in the field of endothelin to our newborn labs -- or lab at Actelion in 1998. There, he told me that in a week, he was going to publish in the JNeurosci the discovery of a new peptide, which he had called orexin, and its receptor. For 2 reasons, we immediately started working on orexin. First, orexin was produced by an extremely small number of cells in the brain, therefore, probably playing an important role. And second, the receptors were members of the G protein-coupled receptor family, the GPCR family, which was and still is one of our key domains of research for drug discovery. We soon realized the incredible potential of orexin receptor antagonist for providing a completely new way of inducing sleep and a very natural sleep architecture. And we were the first to prove, we published this data in Nature Medicine, that the orexin receptor antagonist was able to induce in humans a very healthy sleep, giving a huge hope for patients with insomnia, a field where there has been very little progress in therapy for many years. Our initial work led us to almorexant, but its development had to be stopped because of an unexpected drug-drug interaction. However, we learned a lot through this clinical experience. We knew which type of side effect to avoid and we saw that we could still improve on the pharmacokinetics, but we were convinced that we should pursue this approach. We decided to persevere. We immediately established a new discovery program to find the optimal dual orexin receptor antagonist. Next slide, please. Slide 5. The goal for our research team was a very difficult one. We wanted a dual antagonist, which would have a rapid onset of effect; a duration of action sufficient for the night but short enough to avoid any negative residual activities the following morning at optimally effective doses. The goal was to allow all the next-day benefits of fully restorative night. It took more than 25,000 compounds after almorexant and 9 years. We filtered out compounds as we measured them against several sequential strict criteria, which you can see here on the slide. For the estimation of the human pharmacokinetic and the selection of the optimal future candidate, we developed computer models based on animal and existing human data, including those of almorexant, to best predict the pharmacokinetic and pharmacodynamic behavior and model sleep duration at optimal therapeutic doses. The results we share today have made it all worthwhile and proved that we were right to persevere on the project for over 20 years. I am incredibly proud of the discovery team that created daridorexant. To see now the culmination of this effort in the Phase III study results is key for our researchers. I will now let Guy show you these great results. Guy, next slide, please, the floor is yours.

Thank you, Martine, and good afternoon, good morning, everybody. In the next 15, 20 minutes, I would like to, of course, present the top line results of our efficacy and safety study from the first Phase III study that we just recently completed with daridorexant. But before that, I will remind you on the design of the program and the trials and highlight that we really consider the patient at the center of this program, and this is because we have a vision of insomnia, which I will first like to share with you. Next slide, please. So we must be on Slide 7 now. The vision that we have on insomnia is that, of course, it's a disease of the night, and we know that is defined by difficulty falling asleep, staying asleep or waking too early; but as well as impacting daytime performance of the patients, impacting their daily functioning, causing distress. This is part of the full definition of insomnia. And when we ask patients as to what they expect from the pharmaceutical intervention to improve their sleep, the 2 things that come at the highest level are: number one, they want to increase in total sleep time, an increase in their total sleep time; and number two, they also want to improve their daily performance. Knowing this from our own research, we have decided to include some of these assessments, in particular, the improvement in daily performance into our clinical program. And you will see that in a few moments. We couldn't do that in the Phase II studies, but we were sure that this would be very important with a product like daridorexant and the properties that Martine described. We were sure that it would be absolutely essential to demonstrate that the product not only works during the night but also is able to improve the functioning of the patients during the day. So to align the concept, our vision of insomnia and the development program, we define the assessment criteria to assess, as shown on the next slide, the night and the day, Slide 8. We see here on the left-hand side of the slide, the traditional objective sleep parameters. This is objective quantification that is absolutely needed to be sure that the drug does the job and this is achieved by polysomnography recorded in the sleep lab. It's very useful. However, it has some level of artificial situation because the patient doesn't sleep in his normal environment. And this is what we have on the right side of the slide that we have patient-oriented outcome daily recording of the patients -- by the patients sleeping in their home setting as normal and we have 2 sets of instruments. The first one, which we call the sleep diary questionnaire, SDQ, which is focusing on parameters of sleep. And on the right-hand side of this, second part, we have what we call the Insomnia Daytime Symptoms and Impacts Questionnaire, also called IDSIQ, which is collecting how the patient functions during the day. On the next few slides, I will bring a little more detail on these different assessments. Next slide, Slide 9. So this is the traditional objective sleep assessment, which is, of course, needed, especially from a regulatory perspective. It's essential for submission, in particular in the U.S. And with that, we can objectively quantify how the patients are sleeping during the night. It's very useful to assess insomnia objectively. It's very useful also to characterize the population at baseline during -- and to be sure that we randomize the right population with sufficiently severe insomnia, and I'll come back to that later. It's very useful to establish the solid baseline during the placebo run-in that we have in the trial so that we know where the patients are before taking the medication. And of course, it's very important to measure the primary end point. We did that at month 1 and month 3, looking at 2 particular parameters collected during the polysomnography: latency to persistent sleep and wakening after sleep onset. In addition to that, these parameters are also -- this recording of polysomnography is also very important to assess the potential for rebound as well as to collect a lot more information on total sleep time and especially on sleep architecture. As you can imagine, we have a lot of data to continue to explore in the next few weeks. And I won't be able to talk about everything, but I will focus later on the primary end point. Slide 10. Next slide, please. Here, we see what I call earlier the sleep diary questionnaire, the SDQ, which is daily recording by the patient of their sleep parameters. There are 2 components to this SDQ. There is a morning questionnaire that is assessing through 10 questions the night of the patient and one of the questions, of course, is related to total sleep time that will be used as secondary end point. And here, we talk about subjective total sleep time. Subjective, meaning that it's recorded by the patient themselves. And we have also a number of additional assessments with the visual analog scales that are designed to measure the quality of the sleep, the deepness of the sleep as well as the feeling in the morning. And this is particularly important because one of the targets for an insomnia product is to be able to show whether there is bad feeling in the morning or not. And I can tell you that, that was very important in the daridorexant program. In addition to the morning questionnaire, the SDQ has also an evening questionnaire, which contribute as well to the assessment of the insomnia in patients. There are 2 questions related to napping during the day, and there are 2 visual analog scales related to alertness and ability to perform. Today, on the sleep diary questionnaire, I will only show you the data collected in the morning questionnaire corresponding to total sleep time as one of our secondary end points. On the next slide, I can describe briefly for you what we call the IDSIQ, which is a subjective assessment of daytime performance. This questionnaire has been developed by Idorsia over a number of years -- Actelion in the past, Idorsia now. And as you see on the left-hand side of the slide, a number of items corresponding to 14 questions that every day the patients are answering. And these questions are really targeting things like how the patient can concentrate, how the patient is worried or frustrated or irritable, how the patient is energetic or mentally tired or physically tired, for example. And this is a daily questionnaire. You see on the right-hand side the device, electronic device that is collecting this information. And in the middle, you see how we have clustered the different questions in relation to different domains. And 3 domains have been described for this instrument: the alert/cognition domain in blue, the mood domain in green and the sleepiness domain in red. The terminology here is maybe not the most appropriate. But as you see, the sleepiness domain includes words like energetic and mentally or physically tired. And this is really a domain that is useful to assess the performance of the patients. And therefore in our study, we used a daytime performance measured by the sleepiness domain score as secondary end point. Of course, all the scores, the total score and the score of the other domains are also collected and will be reported in due time as part of exploratory end point in our study. It's also important to mention that this questionnaire has been developed in accordance to the FDA guidelines and has been blessed by the FDA during the number of meetings we had with the agency. Having now covered the 3 main types of end points, the objective one and the 2 subjective end points, it's now time to remind you on the development program overall of daridorexant. This is shown on Slide #12, the next slide. And I just want to remind you that following the completion of the 2 Phase II studies, one in adult and one in elderly, we designed 2 similar pivotal studies of 3-month duration in moderate and severe insomnia. These 2 studies were similar, almost -- actually identically designed. They just differ by the doses that were given to the patients. In the study that we are going to report today, the doses were 25 milligram in one arm, 50 milligram in the other arm and placebo in the third arm. The second study that we'll report in the third quarter of this year is looking at the efficacy and safety of daridorexant given at 10 and 25 milligram. The study, the pivotal Phase III studies were, of course, designed to collect efficacy, objective and subjective parameter, as I mentioned earlier, by PSG or SDQ, but also, as I mentioned, the daytime performance assessed by IDSIQ. And of course, it's very important to have replicated results in the 2 confirmatory studies. These replicated results are also important for safety, and we collect safety in both studies based on adverse events, vital signs, biochemistry, hematology, nothing special here, but more important, using next morning residual hangover effect using the visual analog scale that we have mentioned earlier. And also, of course, as you will see in the design of the study, we collect information on withdrawal and physical dependence and rebound insomnia. This program is very large, and included in the Phase III studies, more than 1,800 patients. But it comes on top of a large clinical pharmacology program. We have a list of some of the studies that we completed in healthy volunteers and some in patients like COPD patients or patients with obstructive sleep apnea. It's not the time now to present this pharmacology results, but in due time, we will be very happy to share that with you once we have completed the Phase III programs. On the next slide, we have here a schematic representation, Slide 13. We have schematic representation of the study design, starting with a screening phase of 20 to 30 days, and the screening phase included a single-blind placebo run-in period followed by 3 months' treatment period, double-blind, comparing 25, 50 and placebo. And this is followed by a safety follow-up. And the first part of the safety follow-up is a single-blind placebo run-out period. There are a number of visits along the study periods. And I would just like to highlight the V3 here where we have 2 consecutive polysomnography nights used at baseline during the placebo run-in period. In parallel to that, the patients were, of course, entering every day their data into this handheld electronic device to collect SDQ and IDSIQ information. Then the patients were randomized and at 1 month and 3 months, highlighted here like visit 6 and visit 8. There were, again, a couple of nights, 2 consecutive nights, looking at the PSG recordings. This is followed during the safety follow-up period and the single-blind period, run-out period, by 1 night, V9, 1 night polysomnography designed to collect information on withdrawal and rebounds. And of course, the daily assessment by the patient is continuing also during this single-blind placebo period. Once patients have reached the end of treatment, so the green bar here on that slide, they can either leave the trial or they can go into an extension study, which I didn't mention before, but which is still ongoing. The next slide, Slide 14, is now showing the study objective. They are very classical. The primary objective was to evaluate the efficacy of 25 and 50 milligrams daridorexant on objective sleep parameters in patients with insomnia. The secondary objective was to evaluate the efficacy of 25 and 50 milligrams of daridorexant on subjective sleep parameters and daytime performance in patients with insomnia. And the third objective was, of course, the traditional safety objective, complemented here with assessment of the next morning effect, looking at hangover effect, withdrawal and rebound during treatment discontinuation. The next slide, Slide 15, is detailing, aligned with what I said before, the different comparison we had to do. So starting from the left, the primary end points, as I mentioned, during the night, wakening after sleep onset by polysomnography; latency to persistent sleep, also called LPS. So the first one is called WASO; the second one, latency to persistent sleep, called LPS by PSG. And the secondary end points look at the night and the day patients' feeling: the first one being the subjective total sleep time, sTST, subjective TST, collected with our instrument SDQ; and the sleepiness score during the day collected by the IDSIQ instrument, which I described earlier. And we have, therefore, 4 end points that were important to us. And 2 dose levels, 50 milligrams versus placebo and 25 milligrams versus placebo -- I'm now moving to the right side on the slide -- and of course, we also did this assessment at month 1 and month 3 as mentioned previously. So if we calculate it together, we have 4 end points, 2 dose levels and 2 time points of assessment for a total of 16 comparisons to placebo. And the statistical design of the trial, the power, was done in a way that the study-wise type 1 error was controlled at 0.05 overall. This is very important because based on the results, we would be able to make claims on the different end points. And that was our target: that we could make claims if, of course, the significant level is achieved on all these different dimensions. So I was a bit long maybe on describing the design, but I think it's very important if we want to understand the results to know exactly what we did. Now we are entering into maybe the most interesting part of the presentation, which is the results, starting with the study patient disposition. And as you see here, we had to screen quite a lot of patients, more than 3,000, to be able to randomize 930 patients. And the reason for that is that we wanted to have very well-characterized patient population, including well-characterized, from an insomnia perspective, using the subjective and objective measures during the placebo run-in; and we selected the population of moderate to severe insomnia. 930 patients were randomized, which represent 28% of the screen population. And as you see, the large majority of them, 92%, completed the trial, which is already a sign of the quality of the study as well as the ability of patients to continue on the medication. The majority of them, of course, completed also the run-out period. We didn't lose many patients here. And then more than 40% of the patients decided to participate into the trial, a double-blind extension, where patients from the other previous 2 studies can also enter. The next slide, Slide 17, is now showing the demographics and baseline characteristics of the patients. As you see and as expected from this condition, insomnia, 67%, 2/3 of the patients were female. We have a mean age of 55. And just to remind you, the study included both elderly and adult patients. And this was possible because we had done Phase II in adult and elderly, showing that the dose range that we wanted to explore in Phase III was similar between adult and elderly. And therefore, adult and elderly patients could be treated in the same study with either 25 or 50 milligrams. So the mean age is as expected when you have an elderly and a young population. The body mass index shows that you have about 40% of patients that are just normal body mass index; some are overweighted, 40%; and about 18%, 19% are actually obese patients. The criteria that we had to start the study were -- the BMI had to be between 18.5 and 40. And as you see also interesting parameter, the patients, on average, had quite a long time of insomnia, 7 years as a median time for their disease. The study was large and conducted in many hospital centers, 75 and in 10 countries. And you have the list of countries, with U.S. and Germany contributing each for 1/3 of the patients. And we are very happy to see that we have quite a large database, in particular, in the U.S., which would be important for the submission to the FDA. On the bottom part of the slide, you see the characteristics of the patients. We included patients that have well-defined insomnia based on subjective parameters on the middle and objective polysomnography parameters on the right, both for sleep induction, sleep maintenance as well as total sleep time, and you have the numbers here on the slide. Now going to the results, Slide 18. And this is really what we were very, very happy and Jean-Paul was talking about. The study demonstrated the efficacy of daridorexant in inducing and maintaining sleep. This was statistically significant for LPS at month 1 and for WASO at month 1. This was also significant at month 3 for LPS and WASO, showing that the effect observed at month 1 was actually sustained at 3 months. There was no attenuation of the efficacy between month 1 and month 3. So we won here on the objective parameters that are essential for registration, these were the primary end points, the 2 primary end points. The next slide is showing the subjective sleep parameter collected by SDQ, the total sleep time subjectively recorded by the patient every day. And here, again, we had statistically significant improvement in sTST at month 1, which was totally maintained at month 3 with, again, statistically significant improvement at month 3, and this was observed for the dose of 50 milligrams as well as the dose of 25 milligrams versus placebo. And the last one, the fourth end point, the IDSIQ parameter. Collecting information on daytime performance with our IDSIQ questionnaire showed at 50 milligram, there was a statistically significant improvement in the IDSIQ sleepiness domain at month 1, an effect that was maintained at 3 months, statistically significant again. And this is, I believe, the first time that a product given for insomnia has been shown to also produce improvement during the day. At 25 milligrams, we didn't quite achieve the statistical significance, but we had a very clear numerical trend in favor of daridorexant versus placebo at both months 1 and 3. So these are the top line results that we have from an efficacy perspective, meeting objectives on all our primary and secondary end points for the 50 milligrams, and most of them for the 25-milligram dose. Now of course, it's important to put the efficacy in the perspective of the safety information, which is shown on Slide 21. This is an overview of the treatment-emergent adverse events. You have the list on the lines, and you have the column -- the blue column for 25 milligrams, the green for 50 and the placebo column on the right. And you see that there was a similar number of adverse events during the double-blind study period in all 3 treatment groups. The adverse events leading to premature discontinuation were extremely low. You have very, very few serious adverse events, and the list is given below. There were very few, what we call, adverse events of special interest, which are adverse events of somnolence in particular or particular observation during sleep, hallucinations or confusions. They were adjudicated blinded by an independent committee, and you see that there are just a handful number of events of special interest. And we had 1 fatality in one group, the 25 milligrams, and the detail is given here. That was based in the 78 -- of a 78-year old male patient going to emergency room with chest pain and dying of cardiac arrest, and that was a patient with multiple risk factors for this event, of course, not attributed to the drug according to the investigator. Going into more details on the adverse event profile, this is shown on the next slide, Slide 22. And we see here on the top, the most frequent adverse events observed. You see that there is not really much to comment on. And on the bottom, you see the more relevant one. They are not that frequent but maybe considered more relevant by our clinicians. You see the frequency of somnolence here, very, very low. And in particular, no difference in somnolence comparing daridorexant 50 milligram, 1.6%; versus placebo, 1.9%. And you see the same pattern for the different adverse events that are relevant here. There is really no signal. Maybe of note, we are all concerned that insomnia products may actually induce fall during the night, in particular. And as you see here, most of the falls, 10 in total, were observed in the placebo group with only 1 recorded on daridorexant 25 milligram and 1 on daridorexant 50 milligrams. So with this data, the efficacy data and the safety data we have, we think that we can now move to the main conclusion of the trial, Slide 23. We observed a very consistent efficacy across the objective and subjective end points across doses and across time points. And you have here a schematic representation of all the end points that I've described to you. Whether LPS, sTST and the IDSIQ end point, we see the significance marked by a tick at 1 month, 3 months, 25 milligrams and 50 milligrams. And we see that out of 16 hypothesis testing comparing daridorexant versus placebo, 14 of them have met the threshold of being statistically significant. And you see on the right-hand side of the slide a summary, high-level summary of the safety and tolerability of daridorexant, the rate of adverse event similar between placebo and daridorexant for those that are primarily -- of primary interest as well as based on the frequent of observed adverse events. I didn't mention the data on next morning, but based on the facts that we have, we don't see next morning hangover effect. We also don't see any sign of rebound insomnia in the polysomnography recordings, and we didn't collect -- we didn't see -- we collected but we didn't see an excess of adverse events during the withdrawal period that would suggest withdrawal symptoms. With that said, I would like now to hand over to Jean-Paul, and maybe you can move to Slide 24.

Thank you, Guy. And again, congratulations because -- since I am not with you, but I still want to congratulate the team for this fantastic development. I hope you -- I think everybody can see how large and well designed is this program and also how informative it is. It's really describing this drug and, of course, we still have to wait the second study, but the second study has the same design. It's just the doses which are different, it's 10 and 25 milligram. But when I see the extent of the effect and also the statistical significance of the 25-milligram dose in this study, I am very confident that we can confirm and even describe even better the dose relationship of this drug in the future. So I think that with daridorexant, we have a unique drug, which is completely disrupting the treatment of insomnia because not only you can really have the patient sleeping faster, sleeping longer, but you can really -- what is the most important for me, you can improve their functioning during the day. And I think that with such a drug, we are really, as I said at the beginning, at a turning point at Idorsia because I think that now with this data, we can move on, we can proceed and we can create a commercial organization, which is going to be responsible of selling this drug. I think that with Idorsia, we can create a fully-fledged biopharmaceutical company. And I have to say, it's going to be very exciting. The next coming months and years are going to be very exciting. But before I hand over to Andrew and hand over for the questions, I really would like all the shareholders, all the investors, who, during the 3 years since -- nearly 3 years since the creation of Idorsia, these investors, these shareholders have trusted the employees, the management and the Board of Idorsia. And I really hope that you are going to accompany us because it's going to be a very, very interesting coming years. Thank you.

Thank you, Jean-Paul, for this exciting presentation. I doubt that anybody in this call has been able to doze off. Last slide, please. We have come to the end of our prepared remarks and are now ready to take your questions. [Operator Instructions] Jean-Paul, Martine and Guy are here to address your questions, but I do need to remind everyone that this is a specific call on daridorexant Phase III study. Hence, please keep your question in this context. We're very confident that we have -- will be -- in the future, have the reason to discuss our commercial strategy, but now is not the time. Operator, first question, please.

[Operator Instructions] We've got the first question from Nick Nieland from Citi.

It's Nick Nieland at Citi. So I'll start with 2 questions. So based on what we've seen so far, if you get to show data on the 10-milligram dose that shows sufficient efficacy, is it likely that you would seek approval for all 3 doses based on this data? Second question is, the positive trend on next-day functioning with the 25-milligram dose, is that strong enough that it could be perhaps pooled with the second study to demonstrate statistical significance?

Nick, thank you for your 2 questions. Guy, I think those are both for you: the one on the data for 10 milligrams and potentially can we group 25-milligram data in the future.

Yes. Thank you for the question. Maybe one step back to explain why we choose 10 milligram as well. We did the Phase II program with 10, 25 and 50 milligrams. And to our surprise, during the Phase II studies, and that was common to the 2 studies, we saw quite a large effect of 10 milligram on LPS -- not much on WASO but on LPS, yes. And with increasing doses, we could see a much better effect on WASO, not much again on LPS. And now what we -- the surprise a little bit was in the Phase III study that we saw a much larger effect on 25 milligram and 50 milligram that we had anticipated based on the Phase II results on LPS. I can't tell you, of course, what the results of the 10 milligram in the Phase III study is going to be. I'll be surprised that the 10 milligram would be at parity with 25. But of course, if it's significant, we may face the situation that the 3 dose levels are relevant. The 50, we find it very, very attractive based on the efficacy and the safety profile. The 25 is extremely promising as well, but we need repetition, and the 10 milligram would be a discovery from the [ 302 ] study. Now turning to the second part of your question, which I think is something we've been looking at, of course. We have a very nice trend on 25. It's not quite significant. But of course, the 2 studies can be pooled, and this is something that we have preplanned before the unblinding of the trial. So there will be a pooled analysis of the 2 25 arms as well as the placebo, of course. And of course, I should add that by doing that, we dramatically increase the power of the trial.

Could I squeeze one more? And that is just have you seen enough data so far to determine that the drug-drug interaction, which caused the termination of almorexant, is not present with daridorexant?

Excellent question. I'm not quite sure -- Martine, do you want to take that one?

Yes. We don't have a problem with daridorexant.

So we have solved this issue.

We have solved the issue.

I think that's -- I think that's a very clear statement.

From Philippa Gardner, Jefferies International Ltd.

It's Philippa Gardner from Jefferies here. I was just wondering in terms of the comments that you had that you had some cases of excessive daytime sleepiness and complex sleep. Can you tell us how these were split across the arms in the trial? Were these all in the active [ 3 and 4 cohort ]?

Thank you, Philippa. Okay. So if I understood the question properly, you wanted to understand -- I think you wanted to understand whether the narcolepsy-like symptoms that are broken down in 4 and 3, how are those broken down. Guy, do you want to shed some color on why we have those numbers like that?

Yes, we can't -- I'm sorry that we cannot describe them more fully. Because the [ 303 ] study being still ongoing, if we were disclosing the details of a single patient -- because we talk here about units of patients, we don't talk about a sufficient number of them, so by disclosing the treatment group, we would actually unblind the study and compromise the data integrity. But as you can see, they look quite balanced. And especially I would point you on the placebo and 50 milligram, we really don't see much of a difference. There is 1 on one side, 2 on the other side. And we certainly don't see a dose response here because there are slightly more on 25. But I can't give you more comments on that because I would take the risk of unblinding people, and that would compromise the data integrity and the submission later on. I'm sorry that I have to tell you that.

We've got one more question from -- sorry, if I don't speak the name correctly, Graig Suvannavejh, Goldman Sachs.

Congrats to the team on the positive results. My questions have to do with -- and I know we don't have a lot of details in terms of the actual efficacy measures and the numbers and the granularity. But my question -- my 2 questions would be when would you -- when are you planning to share the details? I know the SLEEP conference is upcoming as well as ESRS later in the fall. So just wanted to know when you think the actual graphs and tables and more details around this study would be available. And then my second question is related to how -- based on this data and data that we have to other competitor programs with this mechanism of action, how do you see this program currently differentiating versus Belsomra and Dayvigo?

Thank you, Graig. All right, Guy, I think the publishing strategy, you can elaborate well on. With regards to data, I think we can say what is differentiating for us. I don't think we necessarily have to then go into the competition.

Yes. Okay. So we are, of course, working on the publication plan. As you mentioned with the SLEEP conference, with the ESRS Congress, we also plan, of course, a full publication in a journal. It's -- we are just in the time where it's a bit difficult to do the planning because the SLEEP Congress was in June, very timely. And now we believe that it's going to be around August. We want to hear from SLEEP exactly when it's going to be. But the plan is that we are going to communicate as quickly as we can before the end of the year some of these results, and you will contemplate that, I hope, before the end of this year. In parallel, we work on a full manuscript. Based on -- the second part of the question, sorry, was?

It was orexin receptor antagonist, Guy.

Yes, of course. Yes. As you have seen, we have unique results. It's very, very difficult to compare. And it's not the purpose here to compare between products. We have data that are just unique. Nobody has ever done what we did, nobody has ever shown that, i.e., that when you improve the night, you, in parallel, improve the day, whether that mode of action links are due to the product characteristics, I can't tell you, but it's certainly unique to our product. And then you combine that with the safety profile and the very limited impact, for example, on the somnolence that you have seen on the slide, you can make your own assessment. What we have is, I believe, totally unique.

I think just to add, just look at the somnolence in the labels of the other drugs. And frankly, you will see that this unique pharmacokinetic profile is paying off. I think that it's a whole difference because if you are twice as long half-life and with huge variability, you are going to have consequences in the -- during the day. And I'm pretty convinced of the fact that we can really show effect during the day, improvement of performance is due to the pharmacokinetic profile of the drug. Of course, the fact that you have a natural -- I think that the orexin, you will get a much more natural sleep is important. But if your drug is too long active, you are going to be sleeping in the morning, there is absolutely no way to get around. The only way to get around is to decrease the dose and then to decrease the efficacy. So in order to compare, you have to say -- to compare with the same level of efficacy. And frankly, I have to say, you will see when the data -- I might be slightly biased, but I can tell you that when we see the whole data, there is not even a question about the comparisons and the differentiation with the other drugs.

Okay. If I could just have a quick follow-on. Could you remind me what the receptor occupancy for daridorexant is and what the tmax levels are?

Martine, do you have that data offhand?

So we -- can you repeat the question? I did not hear it.

Yes. Sure. No, I was just curious if you could remind me what the receptor occupancy is for daridorexant on a percentage basis and what the tmax might be for this compound?

Tmax, maybe, Guy, you want to answer. On the receptor occupancy, so we model the receptor occupancy from the animals. Of course, in man, we cannot know exactly, but what we can tell is that the clinical data have confirmed our hypothesis, which was that we try to estimate from animal experiments and all the human data we could have how much receptor occupancy was needed for sleep. And when would be the concentrations going down under receptor occupancy causing sleep. And we extrapolate all of what we have and modeled what would be required for an appropriate duration of action at optimal doses in the range of 6 to 8 hours. And that's how we did, but I could not tell you now exactly what has been the receptor occupancy.

Guy, on the tmax?

The tmax is around an hour of each other -- around an hour.

Yes.

But of course, this is the tmax, and the concentration, which are active to block the orexin system, reach much before the tmax.

There are no further question in the queue for the moment.

Okay. Are there any follow-up questions that anybody wants to get rid of?

No.

No? Okay. Therefore, on that note, we're about 10 minutes before the full hour. So I want to thank everybody for your participation.

Sorry, Mr. Nick Nieland has a question again.

Okay. We'll take that question, Nick.

I know you said no commercial questions, but I know it's right at the end of the call, and I wonder if I could squeeze in. Would you be amendable to a similar type of deal that you did with Amrix and with GSK? Or how might you go about commercializing? Is that something you can answer?

We are going to keep this drug for us as much as we can. It doesn't mean that in some cases, like we have done in Japan, we can partner for -- if we need a commercial, a big enough commercial sales force, but the strategy is to keep it. When -- you get once in your life in pharma such a drug, so you're not going to give out any value of this drug. So we are going to try to keep for us this drug.

Thank you, Nick. All right. So dear all, on that note, as Jean-Paul mentioned, we're all embarking on a new journey here. It's been 3 years since the creation of Idorsia, and we've advanced, added through it at a breathtaking speed and now we're ready to enter this new era. On that note, stay tuned for more. The next scheduled release is this Thursday, the publication of the first quarter results. Should you have any questions until then, you know where to find me. Until then, I wish you all the best, stay sound and stay healthy. Operator, please close down the lines.

Yes. Thank you very much. This concludes today's conference. You may now disconnect. Have a good day. Thank you.