Dear ladies and gentlemen, welcome to the Idorsia Conference Call regarding the presentation of the Half Year Financial Results, 2019. At our customer's request, this conference will be recorded. As a reminder, all participants will be in a listen-only mode. After the presentation, there will be an opportunity to ask questions. If any participant has difficulties hearing the conference, please press star key followed by zero on your telephone for operator assistance. May I now hand you over to Andrew Weiss, who will lead you through this conference. Please go ahead.
Thank you, Angela. Good morning, good afternoon, everyone, welcome to our call today. We're here gathered to discuss the first half results published this morning at 7:00 A.M. Central European Standard Time. With me on the call are our CEO, Jean-Paul Clozel, our CFO, André Muller, and Guy Braunstein, Head of Global Clinical Development. He is here to discuss with us the data presented at San Antonio on our daridorexant, our dual orexin receptor antagonist. Next slide, please. Before we jump in, I need to remind everyone that we will be making forward-looking statements and that there are risks and opportunities there in investing in our shares. With that, I hand over to Jean-Paul for his introductory remarks.
Thank you, Andrew. Good morning or good afternoon to everyone. It's a pleasure to present to you the progress we are making at Idorsia. The first half of 2019 has been about running our studies and getting ready for the wave of results and news flow approaching soon. As you might imagine, it's a very exciting time. Since the studies are progressing well, we also start the preparation activity for the potential filing of our late-stage assets. Looking a little further into the future, Simon Jose, our Chief Commercial Officer, has started hiring his core commercial team, enabling the development of a commercial business plan, something that we look forward to sharing with you as each of the programs read out. Of course, we first need to deliver the results from our ongoing studies. Next slide. The pipeline has made good progress in the first half of 2019.
We initiated on multiple dose efficacy and safety studies with cenerimod for lupus. A new compound has started clinical trials in the field of immunology with potential activity in cancer immunotherapy. This is again, a very exciting development from our drug discovery group. These are great steps forward for long-term future. It's the late-stage assets which all eyes are on. If you are interested, you can still find the webcast describing our phase III program on our website. One of the most notable milestones recently was the presentation of the phase II results with our dual orexin receptor antagonist, ACT-541468, newly named with the INN, daridorexant. After a long period of silence, the field of insomnia starts to wake up.
The FDA has just put a black box warning on the Z drug, and several scientific bodies are warning the public of the risk of addiction with this drug. This is extremely sensitive in the frame of the opioid crisis. Since more detailed clinical results are now publicly available and they guided the design of the phase III, I have invited Guy to give you the details and an opportunity for Q&A. Before, I will hand over to André for a brief overview of our financial situation in order to give as much time as possible to Guy and to your questions. André.
Thank you, Jean-Paul. As it was quick, I will be quick as well. We can start with your next slide and see operating results, which is slide number six. From left to right, you have the non-GAAP operating results starting with your revenues. You see here with CHF 13 million, there's no change. This is relating to deferred contracts executed in 2018 with aprocitentan, with J&J for CHF 10.6 million, and a research collaboration with Roche for CHF 2.5 million. Research at CHF 56 million is more or less stable compared to H1 2018, CHF 54 million. Development at CHF 151 million is increasing significantly compared to H1 2018, which was CHF 73 million, so it's more than doubled.
The reason for it is that clinical development with CHF 108 million, has significant variable costs that were incurred in H1 2019, CHF 84 million compared to CHF 32 million in H1 2018. You have pharmaceutical development cost for CHF 43 million. Here again, the fixed cost base is relatively limited, around CHF 13 million, and the variable one with drug substance and drug products for CHF 13 million has also significantly increased. As Jean-Paul said, we are advancing our late-stage assets, and in order to do so, we incur some significant pharmaceutical and clinical development. The G&A, now it's SG&A, with CHF 28 million. This is more or less stable compared to last year, 2018, H1 2018, which was CHF 25 million.
Main increase was relating to the commercial operating expenses with, as Jean-Paul said, our Chief Commercial Officer, Simon Jose, shaping our strategy for our late-stage assets. With this, we have CHF 221 million non-GAAP operating results. You have to add CHF 10 million in D&A and CHF 8 million in stock-based compensation to end up with CHF 239 million US GAAP operating results. Next slide, please. Not much to say, going from operating results to see our net results. The only point here that I would like to recall is that if you're looking at the financial results, which is almost zero for non-GAAP, despite negative interest rate environment, you see a +CHF 8 for US GAAP.
That's the unrealized gain on the Santhera shares that we own in connection with the sub-license that we granted to Santhera on a compound called vamorolone, where we have also an option to in-license it from a U.S. private-owned company called ReveraGen. CHF 8 million is the mark to market, and it can go up and down depending on the stock price of Santhera quarter- after- quarter. For the rest, as you see, almost no income tax, no non-controlling interest.
We end up with CHF 222 non-GAAP net results and CHF 232 million US GAAP net loss. Next slide will show you how we came down with the liquidity. We started the year with CHF 1.2 billion, going down steadily, CHF 108 million on each quarter, Q1, Q2, ending up at CHF 1 billion by the end of June 2019. You see the breakdown on this slide between cash and cash equivalents and some deposits. We try to offset the negative interest rate environment in the Swiss franc. Keep in mind that this CHF 1 billion is mainly held in Swiss franc because we want to avoid any currency risks on our liquidity with CHF 827 million out of this CHF 1 billion.
We have $168 million held in US dollars, also to cover our cash needs in US dollars in the foreseeable future. I have no specific slide on the financial debt because there was no change. We still have the convertible loan with J&J, CHF 376 million in the balance sheet, but nominal value of CHF 445 million, and the convertible bond that we issued last year in July for CHF 199 million in the balance sheet, but a nominal value of CHF 200 million. Next slide, please. Here, you see in connection with the previous slide on liquidity, the cash flow quarter- after- quarter, Q1, Q2.
Here, you see the CHF 108 million that we spend in Q1 as well as in Q2, meaning CHF 216 million for H1 2019, mainly with the funds from operations, CHF 235 million, which are very close to the CHF 234 million non-GAAP OpEx that we were just discussing a few slides ago. You see also in green, the contract revenue, CHF 5 million. This is an upfront that we got in Q2 2018. Please refer to the note four of the financial statements. That's an optional license and/or research collaboration for our T-type calcium channel blocker that we want to investigate in epilepsy.
The undisclosed potential partner will be able to opt in after the FDA feedback based on the IND that we plan to submit in Q4 2019. We should know by the end of this year or very early next year, whether this partner will opt in. Opt-in would consist in CHF 50 or CHF 57 million upfront opt-in milestone, including the CHF 5 million upfront. As you will see in the note four, we would then also get regulatory milestone, phase milestone, and tiered royalties. Finishing with the next slide, the financial guidance. We maintain the guidance with CHF 530 million non-GAAP operating expenses for the full year, which would mean CHF 570 for the US GAAP. You may be slightly surprised if you compare the CHF 234 million that we spent in H1.
Again, as you know, we are going with full recruitment in our phase III assets. This should drive additional expenses into second half of 2018. With this, I hand over to Guy, who will comment on our dual orexin receptor antagonist, as Andrew said previously.
Thank you very much, André. If we're on slide 11, you can move straight to slide 12, which introduce you the name daridorexant, as mentioned by Jean-Paul. You see how you can spell this name on that slide. I'm going to summarize for you the data that were presented at the Sleep Congress a month ago. Next slide 13. Just as a reminder of the definition of chronic insomnia disorder. It's a combination of night and day symptoms as per the DSM-5. Patients have difficulty falling asleep, staying asleep. They also wake up too early, and as a consequence, their daytime functioning is impaired. The definition includes the night and the day symptoms. This has to come with a certain frequency, at least three nights a week, and for a chronic period of at least three months.
We have tools in clinical development that we use to measure the different aspects of the disease, primarily, objectively, with polysomnography, where we can measure the latency to persistent sleep, which is the time from the start of the recording of the PSG to the first moment where the patients are sleeping continuously. By that, I mean for at least 10 minutes. We can also measure what we call the WASO, the wake after sleep onset, which is the time spent awake after the sleep has actually started until the lights on, the end of the recording. Of course, we can also measure the total sleep time based on PSG. These are important measures, especially for the U.S. registration of product.
However, there is also a great interest in the patient-reported outcome instruments measuring sleep parameters using diary cards, where patients are recording the time to falling asleep, their time to wake during the night, as well as total sleep time. Also the daytime functioning of the patients, which can use different instruments, one being called IDSIQ, which has been developed by Actelion and Idorsia. This is a schematic representation of insomnia. On the next slide, I will just remind what we have discussed before about daridorexant. There is, as mentioned by Jean-Paul, still a need for safe and effective treatment for chronic insomnia. Daridorexant is a targeted molecule. It's an orexin receptor antagonist. As we know, there is accumulating evidence of the role of the orexin system in the regulation of insomnia, sleep wave, and a role in intimate disorders.
Daridorexant is a potent and selective orexin receptor antagonist. It was selected based on the properties of the product with the idea of initiating sleep onset, maintaining sleep without impairing the next day's functioning. A lot of that is driven by the pharmacokinetic profile of the product, which is shown on the graphical representation with the time on the horizontal axis and the plasma concentration vertically. We see on day one of treatment administration of 25 mg, a peak occurring very early and then sort of sharp decrease over time. When we look at the pharmacokinetic profile later, we see a profile which is very similar, showing that there is no accumulation. This profile, which we have discussed before, is ideal for a product designed for treatment of insomnia patients. This product has gone through phase I studies and through phase II studies.
The phase II studies were reported at the Sleep Congress in June. I'm going now to summarize the results for you, but before that, I would like just to show you the design of the phase II studies. Next slide 15. We conducted two studies in parallel, one in adult patients and one in the elderly patients. The first one in adult was a parallel group design study, duration of four weeks, allowing to look at the effect after a single dose, as well as the durability of the effect over a treatment time of four weeks. At the end of this four-week treatment, there was a short washout period allowing to assess whether there would be withdrawal symptoms. In that study, four dose levels were tested, 5 mg, 10 mg, 25, and 50 mg.
There was also a placebo group, as well as an active control arm, zolpidem. We measured primarily objective and subjective sleep parameters as I mentioned on the slide before. The end of this study was a different design. It was a crossover design. We just focused on the day one and two nights of treatment. We know that the dose response can be established as soon as the drug is taken. A single night or two nights are sufficient to show the efficacy. We didn't need to confirm the durability of the effect in elderly, having shown that in the adult population. We also tested four dose levels identical to the adult study, five, 10, 25, and 50 mg. There was also a placebo group. We didn't have in that study an active control group. Again, objective and subjective sleep parameters were recorded.
On the next slide, we see the schematic of the adult study. The study is a screening phase of 14- 28 days. During that screening phase, we have a running period where two nights were recorded with PSG serving as a baseline. During these two nights, the patients were taking placebo. The screening period was followed by a double-blind treatment period where zolpidem, placebo, daridorexant five, 10, 25, or 50 mg were administered for 28 days. During the first two nights of administration of double-blind treatment, PSG were recorded. We did the same as day 14 and 15, as well as day 28 and 29. As shown on the PSG measurement line, there was also a single-blind placebo run-out phase to look at the control withdrawal effect of the cessation of insomnia in case there would be one.
All along the period, from screening to double-blind treatment, sleep diary card were filled in every day by patients to collect subjective assessments. The next slide 17, shows the patient disposition and the flow of patients. We had to screen about 1,000 patients, these patients enter into the study based on their self-assessment, self-reported history of insomnia, claiming that they are dissatisfied with sleep, with significant distress during the day as well, according to the DSM-5 criteria. They also claim that they have more than three nights per week for more than three months, difficulty to fall asleep, long awakening during the night, and the total sleep time less than 6.5 hours. Insomnia Severity Index of more than 15. This Insomnia Severity Index is on the scale from 1 to 0 to 28, and 15 is the limit of the moderate severity of insomnia.
15-21 is moderate, and 21-28 is the severe insomnia patients. We screen all these patients, and then they were given the sleep diary to confirm with their self-assessment on a daily basis that actually they had insomnia. From the 1,000 patients, 60% could satisfy the criteria and therefore enroll into the PSG running phase. Here again, we had very strict criteria to randomize the patient. The patient had to have objective confirmatory measure of chronic insomnia with a latency to persistent sleep to at least 20 minutes, was effective 30 minutes and total sleep time of less than seven hours. In the end, from the 1,000 patients that were screened, 360 could be randomized because they had a confirmation of insomnia based on the sleep diary as well as the polysomnography.
The next slide shows the baseline characteristics and demographics of the patient. There is no surprise here in terms of the demographics. More female than male as expected. The mean age in this adult population was 45 years. The body mass index was 25, actually between 19 and 32, and the majority of the patients were Caucasian. The study was conducted in 38 sites in the six countries. They are listed here in the sleep hospital centers. On the right-hand side of the slide, maybe more interesting to see the baseline characteristic with WASO at 97.5 minutes, which is more than an hour, an hour and 38 minutes. The same for latency to persistent sleep, about an hour and 12 minutes, and total sleep time, which is just a little bit above five hours.
Similar numbers were recorded subjectively by patients with a WASO of 1 hour and 20 minutes, time to fall asleep of 1 hour, and the total sleep time of less than about 5 hours and 70 minutes. We see here that these are relatively severe insomnia patients overall, and Insomnia Severity Index is at 21, which is right in the middle of moderate and severe. Probably half of the patients had moderate and half of the patients had severe insomnia. It's interesting to look at the study results, and the first one I would like to show is the WASO, which was the primary endpoint. As you understand, the study was a dose-response study, so the results will be shown as dose response. Next slide 19.
We see here on this busy slide on the horizontal axis, the different treatment groups, placebo, 5, 10, 25, and 50 mg. There is a cartoon of zolpidem on the right. On the vertical axis, we see the change from baseline WASO in minutes. We have two lines, the blue line, which shows the results on day one a nd two, and the red line, which shows the results on day 28 and day 29. What we see here is that there is a dose response from placebo to 5, 10, 25, and 50 mg. This dose response is highly significant with a P value of less than 0.001. Similarly, at day 28 and 29, there was also a dose response that was also significant, and we see a nice decrease from placebo to 50 mg.
What is interesting to note is that the placebo effect was actually more marked at day 28, 29, which explains probably why the dose response is less steep at day 28 and 29. The super effect is maintained. It's also interesting to contrast the results with zolpidem, and you can just look at how daridorexant compares with zolpidem on this slide. The second interesting endpoint is the latency to persistent sleep. Again, measured with polysomnography. This is shown on the next slide 20, where we see the blue line. We're using a similar format. The blue line, day one and two, with again, a significant dose response. The red line, day 28 and 29, also significant, with a decrease of the latency to persistent sleep as the dose is increasing.
As we discussed before, objective parameters are interesting, but it's also interesting to look at how patients perceive their change. This is shown on the next slide, where we have using exactly the same format. On the left of the slide, the subjective WASO, and on the right of the slide, the subjective time to falling asleep. As we see, there is also dose response for these four parameters. The significance is not always achieved. As we know, the variability is bigger on subjective assessment. With the size of the study that we had, there was no real hope that all these dose response curves would be significant. What is interesting is to see that there is in general, a nice concordance between the different parameters, objective and subjective. Maybe the next one is even more interesting.
Slide 21, showing a sort of summary measure of how patients are sleeping. Slide 22, next slide. We see here the total sleep time. Of course, we expect total sleep time to increase, and that's why the lines are now increasing, ascending. We see again with the same format. On the left, the total sleep time recorded objectively by polysomnography. On the right, the total sleep time recorded subjectively by the sleep diary by the patients. We see again, very nice dose responses on daridorexant from placebo to 15 mg for all these parameters at day one and two, as well as at day 28 and 29. I cannot just show the efficacy results without briefly talking about the safety. The safety results are shown on the next slide. It's unusually not very busy.
As you see, there are many zeros and very few numbers on that slide. We had, of course, adverse events during the treatment phase, and you see the number of patients with adverse events. The majority were medically insignificant. We have just shown here the adverse events leading to treatment discontinuation. There were a few of them, and you can read the numbers. What is maybe more interesting, and is written in the text on the right-hand side of the slide, that there was no evidence of rebound insomnia and withdrawal symptoms during the short withdrawal period at the end of the treatment period. Also interesting is to look at how patients feel sleepy on the next morning, and this was looked at using the Karolinska Sleepiness Scale as a morning assessment.
This is a scale that goes from one, very alert, to extremely sleepy, nine, and the results are shown on slide 24. Next slide. You see the different doses on the horizontal axis and the mean value for the Karolinska Sleepiness Scale on the vertical axis. The black line shows the baseline data, and it's about between five and six, which is normal, five being the point of being neither sleepy nor alert. What we see on day one and two is that there was not much change between the black line and the blue line, whether on placebo or at five, 10, 25, and 50 mg in the same zolpidem. We see the similar line for the day 15 and 16 with not much of an effect. Again, day 28 and 29.
The change is actually, if there is one, it's more in the right direction, going below, and below is being more alert. There is certainly no signal here of being sleepy in the morning after having taken any of these treatments. These are the results of the adult study that were shown at the San Antonio Congress. Moving on to the elderly study. Slide 25 is summarizing the design. As I mentioned, it's a crossover study, we have here a Latin square design with five sequences corresponding to five treatments and five periods. There was also a screening period at the beginning with two placebo nights initially to serve as a baseline, and then for each treatment period, we had two consecutive polysomnography nights at each of those, including placebo. Very classical crossover study.
We had shown previously, years ago, with idoxuridine that this was sufficient to show the response, and we'll see the results in a minute confirming this. The next slide shows the patient dispositions. To be able to randomize 68 patients, we had to screen 139 subjects. The entrance to the trial based on the self-reported insomnia according to the DSM-5. They completed the sleep diary, and they had to pass the criteria of at least 30 minutes time to fall asleep, 30 minutes WASO, and less than 6.5 hours of total sleep time. They do so, 100 of them, then they could go to polysomnography to objectively confirm the insomnia. This was confirmed in 58 patients, which represents 39% of the initially intended population.
Again, we had to screen many more patients to be sure that we had a patient that had objective and subjective confirmation of insomnia. The next slide shows the demographics and baseline characteristics using a similar format as for the adult population. We see again that there is a domination by a female population. The mean age this time is 69, as expected for the elderly population, which has to go from 65- 85. We see again that the subjects were mainly White subjects. Turning on to the right side of the slide, we see the WASO, which is quite prolonged, nearly two hours of awakening during the night. The LPS, latency to persistent sleep, of more than an hour, an hour and 15 minutes. Total sleep time, which is just less than five hours.
We see again, on the bottom of that table, the Insomnia Severity Index 20.5, which is similar to what we observed in the adult population. We have here, again, a moderate to severe insomnia population. Now turning to the study results and starting with the primary endpoint, which is awake after sleep onset. Next slide 28. We see a very obvious dose response with a P value that is highly significant. We see from placebo, five, 10, 25, and 50 mg on the horizontal axis, a sharp decrease of the wake after sleep onset on the vertical axis. The placebo effect was less marked in this population compared to the adult population, and the treatment effect was absolutely obvious at all those levels. In that study, we also showed at San Antonio the result, the WASO by quarter of the night using the polysomnography.
The polysomnography is a recording for eight hours in everybody, we can just look at the first two hours, then the following two hours, the third quarter of two hours, and the last one of two hours. I show on the next slide 29, the results of the WASO, the quarter by quarter, with the symbols of placebo, the first one, then the open square, daridorexant 5 mg. The triangle is 10 milligrams. The open diamond is 25 milligrams of daridorexant, the star is 15 milligrams of daridorexant. We see the four panels of subsequent quarters during the night. What we see is that not only there is a dose response at each quarter, but it's becoming more and more pronounced as the night is evolving.
This clearly shows that the effect of daridorexant is maintained during the entire night period. The next slide 30, using the same format as for WASO, is showing the latency to persistent sleep. Again, the polysomnography. We see again, a very significant dose response when moving from placebo to five, 10, 25, and 50 mg, and the P value gives you the significance of this dose response. The placebo effect was less marked on the WASO, but the dose response was still prominent. During the night of treatment, the patient also filled the sleep diary, and the results were also presented. I'm showing you on slide 31 the results of WASO and latency to sleep onset. Again, using the same approach. On the horizontal axis, the dose of daridorexant, and the time on the vertical axis.
We see a decrease in subjective WASO on the left, and a decrease in the subjective time to falling asleep on the right. This actually may be better summarized on the next slide, which shows the total sleep time, subjectively and objectively. Next slide 33. We see here placebo, five, 10, 25, and 15 mg of daridorexant on the horizontal axis, and the time on the vertical. Increased total sleep time. Again, we have a very nice dose response. This is shown for the total sleep time as well as for the subjective total sleep time recorded by the sleep diary. Again, maybe the safety results are shown on the next slide. We see that slide 33, there are very few events. Some qualification on the right side, you can read that. There's really very little reason to worry on the safety of daridorexant in this population.
The next slide 34, shows using the same approach as in the adult population, the Karolinska Sleepiness Scale, assessed in the morning. We see the baseline with a score that is around five, as expected. There is certainly no increase after the treatment the next morning. If any, the move of the score is down, which is showing you being more or less. The conclusion that we can draw from the phase II, next slide 35, is that in both the adult and elderly patients with chronic insomnia, daridorexant does definitely improve sleep onset, sleep maintenance, and total sleep time. Daridorexant was well-tolerated. There was no detectable residual next morning effect at any dose using the Karolinska Sleepiness Scale. Based on these results, we selected three dose levels, 10, 25, and 50 mg of daridorexant to go through the phase III program.
Just in a matter of conclusion, I will show you briefly what the phase III program is now. Slide 36. We have shown here two studies ongoing with 900 patients each, combining in total 1,800 patients, and both studies include elderly and adult populations. Objective and subjective sleep assessments will be measured, in addition to what we have done in the phase II, we are also going to include the developed IDSIQ questionnaire, which is a patient-reported outcome instrument that is assessing the impact on patients functioning during the day. This was not feasible during the phase II, we could include this instrument in the phase III program. The study will deliver long-term efficacy and safety because these two studies are followed by a randomized, blinded study that will provide up to 12 months of treatment.
This will also allow to look at the residual hangover effect and the withdrawal symptoms and rebounds in between. I must mention also that the phase III program, which is shown graphically on the bottom of the slide, is completed by a clinical pharmacology program, which is running as we speak, including, for example, the driving performance study, the interaction with drug and alcohol, as well as a study on the abuse potential, as should be done with this insomnia or CNS product in general. We are on track to report three-month efficacy and safety results in the first half of 2020, and long-term efficacy and safety results later in the same year, next year. With that said, I will hand over back to Andrew Weiss. Thank you.
Thank you, Guy, for all of your elaborations. Next slide, please. We've come to the end of our prepared remarks. We now have roughly around 20 minutes time to address questions. Operator, please open the lines.
Thank you. We will now begin our question and answer session. If you have a question for our speakers, please dial zero one on your telephone keypad now to enter the queue. Once your name has been announced, you can ask a question. If you find your question is answered before it is your turn to speak, you can dial zero two to cancel your question. If you are using speaker equipment today, please lift the hand before making your selection. One moment, please, for the first question. We've received the first question. It is from Richard Parkes of Deutsche Bank. Your line is
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Mr. Parkes, your line is now open. You can ask your question now. Maybe you are on mute?
Let's go to the next question, please.
Yes. The next question is from Stefan Schneider of Vontobel. Your line is now open please, go ahead.
Can you hear me?
Yes, we can.
Perfect. Thank you. Thanks for my question. I just wanted to have a comment from you, if you may, in respect of comparing your data versus suvorexant and lemvorexant. They also showed some data over the past months in respect to efficacy, which is sleep onset and sleep maintenance, but also on safety, like somnolence and next day hangover effects and so forth. Whether you can put that in perspective versus your data?
Guy, please.
Yeah. This is a difficult question, because we don't have head-to-head with suvorexant. We have just to probably refer to the pharmacokinetics of our product, which has an onset of plasma concentration and the duration at five, which is ideal for an insomnia product. We know from the suvorexant story that there was enough of prolongation of the effect the next day to decrease the dose to a level where the efficacy may be debatable. This is something that we think we are going to avoid. Of course, I can't tell you how it compares, because I don't have a head-to-head comparison, and I don't think it's my task really to speculate on the competition. The data are available for both products that you mentioned. The data are available publicly, and you can also take our data and make your own opinion.
We think we have a product that's differentiated, based on the pharmacokinetics and the pharmacodynamic profile that we have. I do not want to speculate more about direct comparison without having a head-to-head.
Okay. Thank you.
Next question, please.
Thank you. The next question is from Philippa Gardner of Jefferies. Your line-
Oh, hi there. I had a question on slide 24 regarding the Karolinska Sleepiness Scale. I was just wondering, when we look at the zolpidem data, that seems to be very similar to what we're seeing with daridorexant. I was just wondering, were you surprised by this, and were you also expecting perhaps a better improvement in terms of how sleepy people feel the next day with daridorexant? Thank you.
Right. Actually, no. We don't expect a big difference, because we know that zolpidem is good at inducing sleep. It's not very good at maintaining it, which means probably that on the next morning, there is not much of an effect. If already in the middle of the night, there is not much remaining. Where we expect a big difference, but that was not collected in the phase II, is how the patient can function the next day. That's why we are going to collect data in our phase III program. We expect a very good effect on the daytime performance of the subject, if they have a very good night. We know that with zolpidem, they fall asleep quickly, but they also wake up early. There is no surprise to us that they were not sleeping in the morning.
What I would like to know is whether they can function properly during the day, and this is not data that is available.
Okay. Thank you.
Thank you, Philippa. Next question, please.
Thank you. The next question is from Ram Selvaraju of H.C. Wainwright. Your line is now open. Please go ahead.
Hi, this is Edward Marks on for Ram. Thank you for taking the questions. I just have two really quick ones. Just wondering, with the recent approval of Galafold, if that provides any additional favorable context just from a regulatory perspective regarding lucerastat. Then if you could just talk about clazosentan REACT trial, and just provide a recruitment update on that, please.
Jean-Paul, do you want to take that?
Just to say.
On Galafold. Does the way that Galafold got approved give us an indication as to how the regulatory pathway for new drugs in Fabry can be?
I think it was a big surprise for us to see Galafold approved, because the FDA told us that they need clinical endpoint. I think that, frankly, we need a clinical endpoint. We need to show benefit. As a CEO, I do not want to really launch a drug without knowing the clinical benefit. This is really what we're trying to do. For the first time, we are trying to get to see if the patients really feel a change and feel better and have less pain, because 70% of patients with Fabry have this neuropathic pain, sometimes less severe, sometimes more severe. Our trial is a trial based not only on how the drug works on all the systemic effect of the Fabry disease, but also how people feel, and do they have less pain.
I think that we are very pioneer in this respect, and I really hope we can show a benefit to the patients.
The second question was on clazosentan, an update on the recruitment.
It's moving well. As you know, we have a program in the rest of the world as well as in Japan, both programs are actually running well. We have no issue, nothing to report at the moment.
The timelines that you can see in clinicaltrials.gov basically indicate that the Japanese trial should be ready sometime during the summer of next year, whereas the global or the Western file, so Europe and U.S., should be available in 2021.
Excellent. Thank you for the details. I appreciate it.
You're welcome. Next question, please.
Thank you. We have now a question from Barbora Blaha of Credit Suisse again. Your line is open. Please go ahead.
Hi. Thank you for taking my question. I have actually two questions. The first one is, how long do the patients typically stay on drugs, so in insomnia? Do you think will this period decrease with DORA because it is less addictive? The second question is, Minerva recently presented phase II data of its SORA, selective orexin antagonist, which could suggest that DORA has more an effect on WASO and SORA's more on latency to persistent sleep. Could you comment on this? Do you see a higher need for a new therapy to treat WASO or to treat LPS? Thank you.
Yes. Thanks for these difficult questions. The duration of treatment, with current medications, the main one is zolpidem. This is because of the risk associated with longer treatment with that drug or with benzodiazepine in general. That's the opposite to what we want to do with our product. We think that insomnia, actually, by definition, we talk about chronic insomnia, of course, not episodic insomnia. By definition, it's chronic, and the definition means at least three months. Therefore, a treatment that is given for one month doesn't really have a place in that indication, because the patients are not cured after one month of treatment. With daridorexant, what we are planning to do is a long-term treatment. We don't expect to have dependence occurring. We haven't seen so far any signal of this possibility.
Of course, more data will come from the phase III. We haven't seen any withdrawal symptoms after termination of the treatment after a month. Our clinical program is going to address short-term and long-term efficacy, in a blinded fashion. The two difficult studies have a three-month duration, and then there is an extension, which is still blinded as well, where we measure efficacy and safety during long-term. Everything is in place to show that the duration of treatment can be longer, and we'll have data for this figure in our refreshing program. The second question was?
Daridorexant.
Yeah.
For Minerva.
Yes. I will not comment on Minerva, but your question is interesting. Orexin one receptor antagonist versus dual, and whether one is useful for sleep induction and the other one for wakefulness. If you look at the dose response that we have with our product, you see that actually, I don't know whether what you said is a speculation or real. Everything is possible. What you see with our product is that a low dose is sufficient to induce sleep. I don't know how much blockade we had at that dose for one versus two. If we can go back to the slide, maybe. Can we go back to slide 30? We see a very, and it's the same for the others, but maybe slide 30 is more accessible.
You see that the maximum effect on sleep latency for inducing sleep is actually achieved at the 10 mg dose. If you contrast that with slide 29, where you see that there is an effect. Slide 28, you see a very different profile where 10 mg has an effect on wakefulness, if you increase the dose, you get a much larger effect. I don't know if this fits with a potential story of orexin 1 versus dual. It's our belief that we need to block the two receptors to have a good effect, and we have seen that with this product on the different parameters.
Just to complete, because this was another question, what does the need for the clinical need, is it WASO or LPS?
Yeah. Just go on, Jean-Paul.
I think really with all the market analysis that we are starting to do, we really see that the big need is the sleep maintenance. Certainly, because zolpidem doesn't do anything on sleep maintenance, and therefore, this is a very big medical need. I think also what I would add personally is really, I think the danger of having too fast-acting drug. It's like in cardiovascular, you do not want to have antihypertensive which works too quickly because then you have the risk of hypotension. It's the same with a sleeping pill. In elderly, we do not want that an elderly person fall asleep when he's still in his armchair, he's not in his bed, and we do not want to have, and we didn't look for having drugs which would work in chronic insomnia. I think this is a very specific for chronic insomnia.
We do not want to have drugs which works too quickly because they are difficult to manage, and then they will have some restriction by regulatory authorities, which might ask, for example, to have the drug taken when the patient is already in bed. I think that frankly, with daridorexant, sorry, I still have a hard time to say it. With daridorexant, we have the ideal pharmacokinetics, not too fast, but long enough. I think that, frankly, I have not seen any other drug with such a profile.
Okay. Thank you.
Thank you, Barbora. Next question, please.
Thank you. The next question is from Richard Parkes of Deutsche Bank. Your line is open. Please go ahead.
Hi. Can you hear me this time?
Yes, we can.
All right, perfect. Yeah, I've got a couple of questions. The first one, you partly answered it with the discussion around the chronic versus acute insomnia, but I noticed that there are additional trials ongoing looking at abuse potential, driving performance, and respiratory function. Could you just update us on your views or your hope for labeling, including expectations for scheduling? I mean, what would be your best case for a label relative to what's out there already? Second question on daridorexant as well. I think you mentioned in the last call plans to partner in Japan. I just wondered if you could update us on how those discussions are going.
Third question, I know Simon is obviously working hard on the commercialization strategy that you'll reveal next year. I just wondered if you could give us some insight into how your thoughts on that are evolving during the process, if possible. Thanks.
I can take the first question, maybe. Of course, we have to do all these studies, and they are all ongoing. It's very difficult to speculate on the labeling. We do as good as we can. We have large studies. We have this program discussed regularly with the regulators. We got a lot of input from them. Everything is there to show the profile of the product. How this profile is going to translate in the labeling, this would be speculation in the future that I cannot do at this stage. It's very clear we are assessing the product, the abuse potential, the driving performance, the impact in COPD patients, in obstructive sleep apnea patients, and many other things are being looked at as well. Everything is there.
How the translation to labeling, I think would be speculating too much, and we'll come back later when we have results of these studies.
Coming back to the regulatory, I think that you might have noted the black box for the Z drug. Really, I think that what is happening today and is that the regulatory authorities still take really more and more conscious of the problem with the Z drug, and they are really looking for alternative to this Z drug. Of course, we need to show that we do not have the same type of issues with the Z drug. This is what we are trying to do, and let's wait for the results, which are going to come very soon. For the Japan, I think that I can say that things are moving, and we will keep you updated when we will be in a more definitive stage. It's clear that I would say that many companies are interested in such a drug.
In terms of commercial strategy, you mean, I think that what we are doing now is really basically analyzing in really depth. Simon is building a team around him with specialists. He's building a team around clearly how to profile, how to brand this drug, but also how to have commercial access, because we clearly know that this is something which we have to solve much before the launch. We have recruited a very good specialist on that. I think that we are now gathering the data, and in the coming months, as soon as we get the results, we are going to define the strategy, and we will keep you updated. I think we really want to build this commercial strategy around data because we want to be able to promote these advantages, this differentiation.
Without having the data, I think it will be very dangerous to completely define the strategy. Let's wait, and this is also coming soon.
Perfect. Thank you very much.
Operator, next question, please.
Thanks. At the moment, there are no further questions. As a reminder, if you would like to ask a question, please press zero one on your telephone keypad now. As we haven't received any further questions, I will hand back to you.
Thank you very much. As you can see, a lot of things are moving ahead these days. We'll keep you posted as to how our advancements are. We are getting ready for this wave of news flow and results coming first half of next year. Please stay posted. Operator, please close down the lines.
Ladies and gentlemen, thank you for your attendance. This call has been concluded. You may disconnect.