Good morning, good afternoon, ladies and gentlemen, welcome to the Idorsia call on phase III clinical data. There will be a presentation, there will be open the call for question and answer. All participants are currently on a listen-only mode. 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, I welcome everybody to our call devoted to the exciting initial data from the first pivotal study 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. 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 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. 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. As you mentioned, in this COVID time, I hope that all of you listening are in good health. I can tell you that at Idorsia, we are all very happy, but we are still thinking of the very difficult situation for many patients, for many practitioners. 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 confinement, and it has been a really incredible effort to get to this data. Guy will show you the top-line result of the study, and you will see that the data are really very important. They are scientifically very important, and therefore, we need to preserve 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 insomnia 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, 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. Also the design and the execution of the clinical program has 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. 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 had 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 journal Cell, the discovery of a new peptide, which he had called orexin and its receptor. For two 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.
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 antagonism for providing a completely new way of inducing sleep and a very natural sleep architecture. We were the first to prove, we published this data in Nature Medicine that an 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 had been very little progress in therapy for many years. Our initial work led us to almorexant, 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. 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 five. The goal for our research team was a very difficult one. We wanted a dual antagonist, which would have a rapid onset of effects, a duration of action sufficient for the night, but short enough to avoid any negative residual activity the following morning at optimally effective doses. The goal was to allow all the next day benefits of fully restorative nights. It took more than 25,000 compounds after almorexant and nine years. We filtered out compounds as we measured them against several sequential strict criteria, which you can see here on the slides.
For the estimation of the human pharmacokinetic and the selection of the optimal future candidates, 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 dosing. The results we share today have made it all worthwhile and prove 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. Before that, I will remind you on the design of the program and the trial, and highlight that we really consider the patient at the center of this program. This is because we have a vision of insomnia, which I would first like to share with you. Next slide, please. We must be on slide seven now.
The vision that we have on insomnia is that, of course, it's a disease of the night, and we know that it's defined by difficulty falling asleep, staying asleep, or waking too early, but as well as impacting daytime performance of the patient, impacting their daily functioning, causing distress. This is part of the full definition of insomnia. When we ask patients as to what they expect from a pharmaceutical intervention to improve their sleep, the two things that come at the highest level are, number one, they want to increase in total sleep time and 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. 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 patient during the day. 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 eight. 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. 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. This is what we have on the right side of the slide, that we have patient-oriented outcome, daily recording of the patient by the patient, sleep in their home setting as normal. We have two sets of instruments. The first one, which we call the Sleep Diary Questionnaire, SDQ, which is focusing on parameters of sleep. 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 nine. 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. 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, to be sure that we randomize the right population with sufficiently severe insomnia. 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. Of course, it's very important to measure the primary endpoints. We did that at month one and month three, looking at two particular parameters collected during the polysomnography, latency to persistent sleep and wake after sleep onset.
In addition to that, 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 endpoints. Slide 10. Next slide, please. Here we see what I call earlier the Sleep Diary Questionnaire, the SDQ, which is a daily recording by the patient of their sleep parameters. There are two components to this SDQ.
There is a morning questionnaire that is assessing, through 10 questions, the night of the patient. One of the question, of course, is related to total sleep time that will be used as secondary endpoint. Here we talk about subjective total sleep time, subjective meaning that it's recorded by the patient themselves. 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. 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. 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 contributes as well to the assessment of the insomnia in patients. There are two questions related to napping during the day, and there are two 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 endpoints. 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. I told you in the past, Idorsia now, as you see on the left-hand side of the slide, a number of items corresponding to 14 questions that every day the patient answering.
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. This is a daily questionnaire. You see on the right-hand side the device, electronic device that is collecting this information. In the middle, you see how we have clustered the different questions in relation to different domains. Three 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. This is really a domain that is useful to assess the performance of the patient.
Therefore, in our study, we use daytime performance measured by the sleepiness domain score as secondary endpoint. Of course, other 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 endpoint 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 a number of meetings we had with the agency. Having now covered the three main types of endpoints, the objective one and the two subjective endpoints, it's now time to remind you on the development program overall of daridorexant. This is shown on slide number 12, the next slide.
I just want to remind you that following the completion of the two phase II studies, one in adults and one in elderly, we designed two similar pivotal studies of three-month duration in moderate and severe insomnia. These two studies were similar, almost, actually, identical in design. 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 mg in one arm, 50 mg 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 mg and 25 mg. 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. Of course, it's very important to have replicated results in the two complementary 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. More important, using next-morning residual hangover effect using the visual analog scale that we have mentioned earlier. Also, of course, as you will see in the design of the study, we collect information on withdrawal and treatment-dependent and rebound insomnia.
This program is very large and included in the phase III studies more than 1,800 patients. It comes on top of a large clinical pharmacology program. You 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 these pharmacology results. 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. I'm sorry. We have a schematic representation of the study design, starting with a screening phase of 20-3 0 days. The screening phase included a single-blind, placebo run-in period, followed by a three-month treatment period, double-blind, comparing 25 mg, 50, and placebo.
This is followed by a safety follow-up, and the first part of a safety follow-up is a single-blind, placebo run-out period. There are a number of visits along the study periods, and I just would like to highlight the visit three here, where we have two consecutive polysomnography nights used as baseline during the placebo running period. In parallel to that, the patients were, of course, entering every day their data into this handheld electronic device to collect the SDQ and IDSIQ information. The patients were randomized, and at one month and three months, highlighted here like visit six and visit eight. There were, again, a couple of nights, two 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 a one-night, V9, a one-night polysomnography designed to collect information on withdrawal and rebounds.
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, after 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 14, is now showing the study objective. They are very classical. The primary objective was to evaluate the efficacy of 25 mg and 50 mg daridorexant on objective sleep parameters in patients with insomnia. The secondary objective was to evaluate the efficacy of 25 mg and 50 mg of daridorexant on subjective sleep parameters and daytime performance in patients with insomnia. 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 15, is detailing, aligned with what I said before, the different comparison we had to do. Starting from the left, the primary endpoint, as I mentioned, during the night, awakening after sleep onset by polysomnography, latency to persistent sleep, also called LPS. The first one is called WASO. The second one, latency to persistent sleep, called LPS by PSG. The secondary endpoint look at the night and the day patient's feeling, the first one being the subjective sleep time, s TST, subjective TST, collected with our instrument, SDQ, and the sleepiness score during the day, collected by the IDSIQ instrument, which I described earlier. We have therefore four endpoints that were important to us, and two dose levels, 50 mg versus placebo and 25 mg versus placebo. I'm now moving to the right side of the slide.
Of course, we also did this assessment at month one and month three, as mentioned previously. If we calculate it together, we have four endpoints, two dose levels, and two time points of assessment, so a total of 16 comparisons to placebo. The statistical design of the trial, the power, was done in a way that the study-wise type I 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 endpoints, and that was our target, that we could make claims if, of course, the significant level is achieved on all these different dimensions. 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. As you see, we had to screen quite a lot of patients, more than 3,000, to be able to randomize 930 patients. 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. We selected the population of moderate to severe insomnia. 930 patients were randomized, which represents 28% of the screen population. 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. More than 40% of the patients decided to participate into the trial double-blind extension, where patients from the other phase II study can also enter. The next slide 17, is now showing the demographics and baseline characteristics of the patients. As you see, and as expected from this condition, insomnia, 67%, two-thirds 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. 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 mg or 50 mg.
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 have just normal body mass index. Some are overweight, 40%, and about 18%, 19% are actually obese patients. The criteria that we had to start the study were that the BMI had to be between 18.5 and 40. As you see also, interesting parameter, the patients on average had quite a long time of insomnia, seven 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 the U.S., and Germany contributing each for a third of the patients.
We were very happy to see that we have quite a large database, in particular in the U.S., which will 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 number here on the slide. Going to the results, slide 18. 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 one and for WASO at month one.
This was also significant at month three for LPS and WASO, showing that the effect observed at month one was actually sustained at three months. There was no attenuation of the efficacy between month one and month three. We won here on the objective parameters that are essential for registration. These were the primary endpoints, the two primary endpoints. The next slide is showing the subjective sleep parameter collected by IDSIQ, the total sleep time subjectively recorded by the patient every day. Here again, we had statistically significant improvement in sTST at month one, which was totally maintained at month three, with again, statistically significant improvement at month three. This was observed for the dose of 50 mg as well as a dose of 25 mg versus placebo.
The last one, the fourth endpoint, ESS parameter, collecting information on daytime performance with our ESS questionnaire, showed that 50 mg, there was a statistically significant improvement in the ESS sleepiness domain at month one, an effect that was maintained at three months, statistically significant again. 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 mg, 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 one and three. These are the top-line results that we have from an efficacy perspective, meeting objectives on all our primary and secondary endpoints for the 50 mg, and most of them for the 25-mg dose.
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 blue column for 25 mg, the green for 50 mg, and the placebo column on the right. You see that there was a similar number of adverse events during the double-blind study period in all three treatment groups. The adverse events leading to premature discontinuation were extremely low. You have 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, you see that there are just a handful number of events of special interest. We had one fatality in one group, the 25 mg, and the detail is given here. That was a death of a 78-year-old male patient going to emergency room with chest pain and dying of cardiac arrest. 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 from the adverse event profile, this is shown on the next 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. On the bottom you see the more relevant one. They are not that frequent, but maybe considered more relevant by clinicians.
You see the frequency of somnolence here, very low, and in particular, no difference in somnolence comparing daridorexant 50 mg, 1.6%, versus placebo, 1.9%. 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 falls during the night in particular, and that you see here most of the falls, 10 in total, were observed in the placebo group with only one recorded on daridorexant 25 mg and one on daridorexant 50 mg. 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 observe a very consistent efficacy across the objective and subjective endpoints, across doses, and across time points.
You have here a schematic representation of all the endpoints that I described to you, whether LPS, sTST, and the IDSIQ endpoints. We see the significance marked by a tick at one month, three months on 25 mg and 50 mg . We see that out of 16 hypothesis testing comparing daridorexant and the placebo, 14 of them has met the threshold of being statistically significant. You see on the right-hand side of the slide, a high-level summary of the safety and tolerability of daridorexant. The rate of adverse events similar between placebo and daridorexant for those that are primarily of primary interest, as well as based on the frequency of observed adverse events. I didn't mention the data on next morning, but based on the data 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, we collected, but we don't see an excess of adverse event during the withdrawal period that would suggest withdrawal symptoms. With that said, I would like now to hand over to Jean-Paul. Maybe you can move to slide 24.
Thank you, Guy. Again, congratulations because since I am not with you, but I still want to congratulate the team for this fantastic development. I think everybody can see how large and well-designed is this program and also how informative it is. It's really describing the drug. Of course, we still have to wait the second study. The second study has the same design. It's just the doses which are different. It's 10 mg and 25 mg. When I see the extent of the effect and also the statistical significance of the 25-mg dose in this study, I am very confident that we can confirm, and even describe even better the dose relationship of the drug in the future.
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. I think that with such a drug, we are really, as I said at the beginning, at a turning point at Idorsia. 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. I have to say, it's going to be very exciting. The next coming months and years are going to be very exciting.
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 three years since, nearly three years since the creation of Idorsia, these investors, these shareholders, have trusted the employees, the management, and the board of Idorsia. I really hope that you are going to accompany us because it's going to be a 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. I ask everybody when you're addressing your question, that you state your name and your affiliation and limit your questions to two. 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'll be, in the future, have the reason to discuss our commercial strategy, but now is not the time. Operator, first question, please.
Yes, thank you very much, ladies and gentlemen. Your question and answer session will now begin. If you wish to ask a question, please dial star 14 on your tone dial phone. If you change your mind and decide to cancel the question, please star 15. Okay, we've got the first question from Nick Nieland from Citi.
Hi, it's Nick Nieland at Citi. I'll start with two questions. Based on what we've seen so far, if you get to show data on the 10-mg dose that shows sufficient efficacy, is it likely that you would seek approval for all three doses based on this data? Second question is that the positive trend on next day functioning with the 25-mg dose, is that strong enough that it could be perhaps pooled with the second study to demonstrate statistical significance? Thank you.
Hi, Nick. Thank you for your two questions. Guy, I think those are both for you. The one on the data for 10 mg and potentially can we group 25-mg data in the future?
Thank you for the question. Maybe one step back, to explain why we chose 10 mg as well. We did the phase II program with 10 mg, 25 mg, and 50 mg. To our surprise, during these phase II studies, and that was common to the two studies, we saw quite a large effect of 10 mg on LPS. Not much on WASO, but on LPS, yes. With increasing doses, we could see a much better effect on WASO, not much again on LPS. Now what the surprise a little bit was in the phase III study that we saw a much larger effect on 25 mg and 50 mg than we had anticipated based on the phase II results on LPS. I can't tell you, of course, what the results of the 10 mg in the phase III study is going to be.
I'll be surprised that the 10 mg would be at parity with 25 mg. Of course, if it's significant, we may face the situation that three dose levels are relevant. The 50 mg we find it very attractive based on the efficacy and the safety profile. The 25 mg looks extremely promising as well, but we need repetition, and the 10 mg 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 mg. It's not quite significant, but of course, the two studies can be pooled, and this is something that we have pre-planned before the unblinding of the trial. There will be a pool analysis of the two 25 mg arms as well as the placebo, of course.
Of course, I should add that by doing that, we dramatically increase the power of the trial.
Thank you. Could I squeeze one more in? That is just that, have you seen enough data so far to determine that the drug-drug interaction which caused termination of almorexant is not present with daridorexant?
Excellent question, and I'm not quite sure. Martine, do you want to take that one?
Yes, we don't have a problem with daridorexant.
We have solved this issue.
We have solved the issue.
I think that's a very clear statement. Thank you, Nick, for your questions. Operator, next question, please.
Yes, thank you. From Philippa Gardner, Jefferies International Ltd.
Yeah. Hi, 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-
All participants' lines unmuted.
Thank you, Philippa. Okay, if I understood the question properly, you wanted to understand.
All participants' lines listen only.
I think you wanted to understand whether the narcolepsy-like symptoms that are broken down in four and three, how are those broken down. Guy, do you want to shed some color on why we have those numbers like that?
Yeah, 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. By disclosing the treatment group, we would actually unblind the study and compromise the data integrity. As you can see, they look quite balanced. Especially I would point you on the placebo and 50 mg. We really don't see much of a difference. There is one on one side, two on the other side, and we certainly don't see those response here because they are slightly more on 25 mg. 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.
Thank you, Philippa, for your question. Operator, next question, please.
Yes, we've got one more question from, sorry if I don't speak the name correctly, Graig Suvannavejh, Goldman Sachs.
Yes, Graig, hi.
Hey, Andrew, and thank you. 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. My two questions would be, when are you planning to share the details? I know the Sleep Congress is upcoming as well as ESRS later in the fall. Just wanted to know when you think the actual graphs and tables and more details around this study would be available. My second question is related to, based on this data, and based that we have two other competitor programs with this mechanism of action, how do you see this program currently differentiating versus Belsomra and Dayvigo? Thanks.
Thank you, Graig. All right. Guy, I think the publishing strategy you can elaborate well on.
Sure.
With regards to data, I think we can say what is differentiating for us. I don't think we need necessarily have to then go into the competition.
Yeah. Okay. We are of course, working on the publication plan, as you mentioned, with the Sleep Congress, with the ESRS Congress. We also plan, of course, a full publication in a journal. 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. Now we believe that it's going to be around August. We want to hear from Sleep exactly when it's going to be. The plan is that we are going to communicate as quick 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 the full manuscript. Based on the second part of the question. Sorry, what?
It was about comparing the orexin receptor antagonist.
Yeah. Of course. Yes. As you have seen, we have unique results. It's very difficult to compare. 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 data, i.e., that when you improve the night, you in parallel improve the day. Whether that mode of action linked or due to the product characteristics, I can't tell you, but it's certainly unique to our product. Then you combine that with the safety profile and the very limited impact, for example, on 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 during the day. I'm pretty convinced that 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 will get a much more natural sleep is important. 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. In order to compare, you have to say to compare with the same level of efficacy. Frankly, I have to say, you will see when the data and the 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?
Can you repeat the question? I did not hear well.
Yeah, 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, 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. 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 six to eight hours. That's how we did, but I could not tell you now exactly what has been the receptor occupancy in man.
The tmax is around an hour of each other. Around an hour.
Yes.
Okay. Thank you very much.
Of course, this is the tmax and the concentration which are active.
To block the orexin system are reached much before the tmax.
Okay, great. Thank you again.
Thank you, Graig. Operator, next question, please.
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. On that note, we're about 10 minutes before the full hour. I want to thank everybody for their participation.
Sorry, Mr. Nick Nieland had a question again.
Okay. We'll take that question, Nick.
Hi, guys. 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 amenable to a similar type of deal that you did with almorexant and with GSK? 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 big enough commercial sales force. The strategy is to keep. You get once in your life in pharma such a drug, you're not going to give out any value of this drug. We are going to try to keep for us this drug.
Right. Thank you.
Thank you, Nick. All right. They're all on that note, as Jean-Paul mentioned, we're all embarking on a new journey here. It's been three years since the creation of Idorsia, and we've advanced at it, 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 safe 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. The conference recording has been stopped.