Good day, thank you for standing by. Welcome to the Idorsia full year 2022 financial results webcast. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one and one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one and one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Andrew Weiss. Please go ahead. Thank you, Heidi. You've reached the mailing list for voice messages. Good morning, good afternoon, everyone. Goodbye. Welcome to our webcast to discuss the full-year publication of our results. The press release went out this morning at 7:00 A.M. Central European Time. With me on this call are our CEO, Jean-Paul Clozel, our CFO, André Muller, and our Chief Commercial Officer, Simon Jose. Next slide, please. Just to remind you, we will be making forward-working statements in this call. Please be attentive to the disclaimer. You've therefore been adequately warned about the risks and benefits of owning or shorting our stock. Next slide, please. Let's kick it off. Jean-Paul, the mic is yours. Yes. Yesterday you have seen that we have informed the market that the REACT study did not meet the primary endpoint. Of course, we are very disappointed and very sad, I have to say. It should not really hide the achievement. Next slide. That happened in 2022, which provide momentum for 2023. Next slide. A lot has been achieved in 2022. First, QUVIVIQ was approved in the U.S. PIVLAZ was approved in Japan and launched in Japan. QUVIVIQ was launched in the U.S. QUVIVIQ was approved in Europe. We got the result of aprocitentan showing a very significant blood pressure reduction. We got the results of daridorexant in insomnia in Japan. The QUVIVIQ at the end of the year, was launched in Germany and Italy. cenerimod, phase III in Lupus was initiated. Finally, just before the end of the year, aprocitentan was filed for U.S. The NDA of aprocitentan was filed in the U.S. Simon is going to describe our commercial plan and the launch of our first two products. Next slide. Thank you, Jean-Paul, and good morning and good afternoon, everyone. 2022 was indeed a transformative year. We obviously launched our first two products, and I believe we built a very strong foundation for future growth. Obviously today I'm pleased to be able to share with you the positive momentum we're seeing with the launches of QUVIVIQ in the U.S. and Europe, and of course PIVLAZ in Japan. Next slide, please. I'll start with QUVIVIQ, which as you all know, was launched in the U.S. in May and in the first two European markets in November, as Jean-Paul said in Italy and Germany. In 2022, net sales totaled CHF 6.5 million. Obviously, as I've mentioned before, net sales in the U.S. don't reflect demand or prescriptions dispensed. To enable early patient access to QUVIVIQ, we continue to offer our strong co-pay program, including a free first 30-day prescription. Of course, demonstrating demand is critical to support our ongoing negotiations to expand payer coverage. I'll provide an update on our progress there in a few minutes. Next slide, please. Turning now to the prescription volume for QUVIVIQ in the U.S. You've seen this slide in prior earnings calls showing the TRX volume by strength on the left and the split by retail dispensers, which you see reported by IQVIA, and those dispensed by VitaCare, our pharmacy services provider on the right. Obviously we've updated these last three months since you saw this chart in October for the Q3 call. I'm pleased to be able to share that TRX volume continues to grow with almost 15,000 prescriptions dispensed in December, despite the usual dampening impact of the holidays, which as you can see, was the case with VitaCare, who were closed for the public holidays during the Christmas to New Year period. We continue to be pleased that the 70-30 split of the 50 milligram and the 25 milligram strengths is, as you can see, being maintained. Next slide, please. You can also see the same positive trajectory in QUVIVIQ writers, which continued to grow month-over-month. Although we continue to expect to see our writer base growing as we move into 2023, our clear focus is now going to be on increasing the number of prescriptions from each writer, turning the current breadth of prescribing into greater depth of use. On the right-hand side, you see the split by prescriptions, with 65% of prescriptions now coming from primary care physicians and 21 coming from psychiatrists. This is broadly in line with the structure of the insomnia market. Next slide, please. Encouragingly, we continue to see the source of business for QUVIVIQ coming from either new patients or where switched from the older, widely used sleep medicines such as Z-drugs, benzos, and trazodone. Only a small number of patients on QUVIVIQ are coming from the other DORAs. Around 6% of switches and only 3.5% of all patients. This is critically important to us, as to achieve our long-term goals, we need to dramatically grow the DORA class, in addition, of course, to making QUVIVIQ the leading DORA. Next slide, please. Here's the effect on prescriptions. You can see that QUVIVIQ volume has essentially been additive to that of BELSOMRA and DAYVIGO, expanding the DORA class as a whole. Naturally, QUVIVIQ is taking share within the class as it grows. The chart on the right shows that after just eight months on the market, QUVIVIQ has achieved 41% share of the DORA class in MBRXs, surpassing DAYVIGO, and in quarter four, it approaches BELSOMRA. During that same period, the DORA class has grown 67%. Next slide, please. Taking a closer look now at how our MBRXs are tracking in recent weeks. You can see here that QUVIVIQ is now neck and neck with BELSOMRA. We expect to become the leading DORA in MBRXs any week now that we are through the holidays and payer coverage is increasing. Of course, refills and continuing prescriptions are just as important as acquiring new patients, arguably more so in the long run. The chart on the right shows the continued growth and acceleration in CBRXs or continuing prescriptions, indicative of the patient satisfaction with QUVIVIQ we generally hear in the market. The MBRX performance versus BELSOMRA is particularly impressive when you consider that BELSOMRA generates over 50% of its prescriptions from Medicare Part D, where QUVIVIQ is yet to be covered. Next slide, please. Although it's clear we would have passed BELSOMRA MBRXs in the commercial segment only, we actually can't get MBRXs by channel, so I can't show you that and construct a graph to sort of prove it. We are able to do this with TRXs. As you can see here, in the commercial segment only, where we can compete equally, QUVIVIQ has passed DAYVIGO TRX share and is on a trajectory that will pass BELSOMRA in the next few months. This is probably the most appropriate head-to-head comparison of performance while we continue to expand our access and before we have Part D coverage. Next slide, please. Of course, speaking of coverage, I'm pleased that we have made some real progress in the beginning of this year. As many of you will now know, QUVIVIQ was added to the Express Scripts National Preferred Formulary from January 15th, gaining parity access with the other DORAs in their approximately 22 million lives covered, representing about 13% of the commercial market. There are a further 30 million lives, about another 19% of the commercial segment in the downstream plans that can now take the ESI rate that we've agreed with them. We're also on formulary with TRICARE, which covers 9 million U.S. military service members and their families, a further 5.4% of the commercial segment. As you can imagine, we are now actively pulling this expanded coverage through via the sales team and other promotional activities. Of course, we're in discussion with all the ESI downstream accounts to secure coverage there too. We continue to have active discussions with the other commercial payers and the Part D plans. Next slide, please. To just conclude the U.S. by briefly touching on our branded direct consumer advertising featuring QUVIVIQ patient ambassadors Lindsey Vonn and Taye Diggs. These initiatives have demonstrated a very significant increase in all our key metrics, including traffic to QUVIVIQ.com, where we now have exceeded 1.7 million visitors. Paid and organic search, co-pay card downloads and utilization, and ultimately doctor conversations and QUVIVIQ MBRXs and continuing scripts. Next slide, please. Looking beyond the U.S., QUVIVIQ is on track to become a global brand. In November last year, we achieved our first European launches in Germany and Italy, and I'll speak more about our progress there in a moment. We've also completed our phase III study in Japan and are preparing to file the marketing authorization application in the second half of this year with our local partner, Mochida. We also announced a licensing agreement with Simcere in November 2022 to develop and commercialize daridorexant in the Chinese market. Next slide, please. In Europe, QUVIVIQ is the first and only DORA available to patients, and I really see great potential here, given the high unmet need and dissatisfaction with existing treatments in the region. In Germany, we launched QUVIVIQ in mid-November, and as I'll show you in a minute, it's got off to a great start. As I've mentioned before, in the German market, there is a four-week prescription limitation for all hypnotic and sedating agents known as Anlage III. The G-BA issued a draft resolution last year to exempt QUVIVIQ from Anlage III, which, if approved, would mean QUVIVIQ would be the only sleep medicine reimbursed for long-term use in Germany for adults. We also launched in Italy last November into the private market, as insomnia products there are not reimbursed. At launch, prescribing of QUVIVIQ is limited to specialists. It's not uncommon for that to be the case with new CNS products, and the feedback to date has been extremely positive. Launch preparations are underway in Switzerland, with launch planned in mid-2023 in the private market. This is whilst our reimbursement dossier is under review. In the U.K., we plan to launch in the second half of this year following final NICE guidance. We submitted our dossier to NICE last summer and will have an advisory committee in March. Lastly, launch preparations are also underway in Spain and France. Next slide, please. Returning to Germany briefly. Whilst it's early days, QUVIVIQ has got off to a strong start in Germany. This chart shows the weekly sales units from wholesalers to pharmacists, and you can see the very positive momentum in the initial weeks post-launch, which has continued now after the dip during the holiday period. There were a significant number of German sites in the pivotal trial programs of QUVIVIQ, and we're seeing a great deal of interest among German medical experts and GPs in the new mechanism of action and differentiated efficacy and safety profile of the product. Next slide, please. Here we see the initial uptake in Italy. This weekly data is projected by IQVIA from a panel of pharmacies around 20% across Italy, so we should treat it with some caution. Nevertheless, we see a positive initial trajectory, especially when considering that we are launching in a private pay market with specialists prescribing only at this stage. We recently had a launch event with key opinion leaders who showed a lot of excitement about the product and shared their positive initial experience with QUVIVIQ. I look forward to sharing more progress in Europe over the next months. Next slide, please. Just to finish up with turning to PIVLAZ in Japan. We launched PIVLAZ, as you know, in April last year to prevent vasospasm following an aneurysmal subarachnoid hemorrhage. This has a two to 3x higher incidence in Japan than we have in the Western markets. Next slide, please. Again, you've seen this chart. It's now been updated with the end-of-the-year numbers. We continue to see very positive trajectory since launch. We generated net sales of CHF 44 million since April, against the currency headwind, I hasten to add, with over 95% of target hospital accounts ordering. Medical experts and neurosurgeons are supporting the inclusion of PIVLAZ in SAH treatment protocols. At the end of last year, in December, approximately 25% of ASAH patients received PIVLAZ based on the incidence of SAH in Japan. We expect adoption to continue to grow this year. In summary, I think 2022 was a transformative year where we put our commercial plans into action and we launched our first two products. QUVIVIQ is building momentum with very positive feedback from physicians and patients alike. In the U.S., we expect this momentum to increase and start translating into net sales as we expand payer access. In Europe, although it's early days, QUVIVIQ is off to a strong start in Germany and Italy, and we're preparing for additional launches later this year. I'm confident the strong foundation we've built in 2022 sets us up for a year of strong growth and additional launches in 2023. Thank you for your attention. I'll now hand over to André. Thank you, Simon. Next slide, please. Let's go directly to slide 23 and how the U.S. GAAP net result came about. I would like us to start with the CHF 757 non-GAAP operating loss of 2022. You may recall that we have not changed the guidance from the full year result 2021, in February 2022, the Q3 results published in October 2022, maintaining net non-GAAP operating results of - CHF 785. You see actually a difference of CHF 28 million. This CHF 28 million is actually the contract revenue on Simcere of $30 million upfront. What I want to emphasize here is that, yes, clearly, sales were lower than expected. But it also means that we closely monitor our OpEx to remain committed to these to these gains. Now coming with a few comments on the net revenues. The CHF 97 million on the top left consists in CHF 50 million sales. As Simon said, PIVLAZ in Japan, CHF 44 million, badly impacted by the FX rate with the weakening of the Japanese yen. And roughly CHF 6 million with daridorexant, U.S. accounting for CHF 5.5 million and Germany for almost CHF 1 million. On the contract revenue, the remaining CHF 47 million, as André Muller said, Simcere accounted for CHF 28 million. We had CHF 2 million from Ponvory, revenue sharing from Janssen, CHF 3 million from Neurocrine, with an extension of the research collaboration, and CHF 14 million deferred contract revenue from a previous collaboration, including J&J, regarding aprocitentan. With this, and we'll in the next slide, we'll comment the non-GAAP operating expenses of CHF 854 million. Our DNA and stock-based compensation in line with the previous years at respectively CHF 20 million and CHF 26 million. Leading to a U.S. GAAP operating results of - CHF 803 million. Below where you see it's at CHF 25 million, which is mainly interest, around CHF 16 million. That's the coupon of 2.125% paid on the CHF 600 million convertible bonds, so for approximately CHF 12.2 million. The coupon on the CHF 200 million convertible bonds, so 0.75%, for CHF 1.5 million. You may recall, I explained it in the Q3 results, the sale and leaseback transaction is according to U.S. GAAP treatment, treating as debt, and to the extent we have also a relating funding cost of CHF 1.6 million. On top of the interest of CHF 16 million, you have also a tax of CHF 8 million, CHF 2.5 million withholding tax on the upfront from Simcere. We had also $4 million of foreign taxes, mainly in Japan and U.S., given our tax organization with our commercial affiliates being what we call limited risk distributors. We have $1.5 million deferred tax. This lead us to a U.S. GAAP net result of - $828 million. Let's move to see our next slide, 24. Speaking of the non-GAAP operating expenses here. Cost of sale is mainly consisting of on the royalties that we pay on the trazodone, so it's $4 million. The real cost of goods and is really low on the sales. For the remaining $2 million, it's really, it's more distribution and warehousing. As you can see, our research with CHF 117 million is almost flat or, I would say flat if you take into account CPI. You see that development is slightly below last year at CHF 240 million. In this CHF 240 million, you have roughly CHF 100 million which are functional expenses. It's a real fixed cost base of our development organization, clinical, but also pharmaceutical and chemistry. The remainder, so approximately CHF 140 million, that's really the study cost. Here we have three main drivers. First, selatogrel. You know, well, we are enrolling with the SOS-AMI. To this extent, we have spent more, significantly more than in 2021 with CHF 41 million for selatogrel. 28 in clinical, so remaining in order to get this auto-injector in connection with mainly Halozyme. The other main driver are daridorexant and cenerimod. Cenerimod, we are now, as you've seen, we have finished phase II. This was the main phase IIb, we are starting phase III. This was the main driver for the expenses, study expenses, around CHF 26 million. The other big driver is the daridorexant with still CHF 26 million. Not so much at in a global clinical, which is around CHF 8 million, notably with the initiation of the pediatric, but also with the Japanese trial. As Jean-Paul said, now we got the results, Japanese pivotal trial accounted for CHF 9 million. That's our share because Mochida, our partner, took also 50% of the local development costs. These are the main drivers. As you can imagine, aprocitentan comes to an end, clazosentan will also come to an end, especially moving forward in 2023. lucerastat still spending because we have an open label expansion. These amounts are relatively small compared to selatogrel, cenerimod, and daridorexant. SG&A. In this CHF 492 million, the main cost is really driven by commercial with marketing and selling expenses around CHF 400 million, of which a significant amount is spent in the U.S., around CHF 300 million. Simon explained you that here we need to have a sales force detailing the PCPs. We need also when you have seen the impact of DTC digital and TV ads. We're set. This was a significant effort, not fully reflected in the net sales, we need first to grow a demand and continue on this positive trajectory to convert demand to volumes into net sales now that we get commercial coverage. Soon, hopefully, as Simon said, also, but that's 2024 with Medicare Part D. With this, we end up with CHF 854 million non-GAAP operating expenses. A significant chunk compared to 2021, mainly driven by the launch activities in the U.S., preparing pre-preparation in Europe and Canada, and also with the launch in Japan. Next slide, please. Cash flow. You know that you'll recall that we started the year with a stronger balance sheet, CHF 1,188 million liquidity. As said, the non-GAAP operating results of CHF 757, we just explained. CapEx around CHF 27 million. Significant working capital requirements with CHF 65 million with an inventory built notably with registered starting material for daridorexant, but also a significant increase in trade receivables. Of course, with Japan sales, you have roughly 100 days of sales outstanding. But also with the U.S. because of the U.S..sales model. You know, we sell to the wholesaler at WAC or gross net or gross selling price. We get a 60-day payment term with this wholesaler. All the gross to net. All the rebates are paid at 15 days. Of course, this generates, because we have demand, because gross sales are going up, we have with this a higher working capital requirement. Sale and leaseback, this was already in Q3 CHF 162. The other items are actually what we already mentioned below EBIT. Interest expense, tax expense, and a small adjustment to reconcile with the non-GAAP operating result. By the end of December 2022, we end up with a liquidity of 466 million Swiss francs. Next slide, please. Here you see the structure of this liquidity by year, by year-end 2022. 336 million on the right chart in Swiss franc, and $116 in U.S. dollar, because that's a natural hedging, notably accounting for the sales, the OPEX, notably with the U.S. commercial organization. Next slide, please. I will finish with the financial guidance for 2023. You see here, net revenue of CHF 230, operating expenses of CHF 880. These are non-GAAP measures leading to a non-GAAP EBIT of CHF 650. As last year, we can be reassured that we are committed to manage this EBIT target at CHF 650 million. If you take a U.S. GAAP, you see a delta between in the operating expense of CHF 65 million, which is mainly driven by a stock-based compensation. With a significant increase. The reason for it is that in order to preserve our cash, 70% of next year or 2023 bonus to employees across the organization will be paid in shares, account for roughly CHF 20 million. If you had time to read the governance report, you've seen that we launch in 2022 a plan called Ambition 2027. With granting to most employees an incentive plan, split evenly between Restricted Share Units and Performance Share Units that will have some metrics in 2025, 2026, and 2027. You still have to account next year or see a full year impact in a U.S. GAAP of this Ambition 2027 new initiative to retain the employees at Idorsia. Lastly, we are growing in terms of organization. You have also a higher impact of the organization in 2023 compared to the previous years. With this, we believe that the U.S. GAAP operating loss would be around CHF 735 million. Next slide, please. You may have seen already this profitability target which we issued at the JP Morgan Healthcare Conference. We remain committed to reach sustainable profitability in 2025 with a global revenue above CHF 1 billion. Here again, we only account what we know, i.e., the sales of QUVIVIQ, the sales of PIVLAZ in Japan only and the tiered royalties that we entitled to with Janssen regarding aprocitentan. With this, I hand over to Jean-Paul. Thank you, André. You have seen that next slide. We are continuing to advance our pipeline and you have heard about next slide. PIVLAZ and unfortunately the REACT, also the Japan commercial success. QUVIVIQ, which is basically to an end of the clinical development plan and the aprocitentan which is five. We are going to during the year have a discussion with regulatory authorities for lucerastat, and we are in phase III recruiting for selatogrel and cenerimod. I will concentrate on these phase III products. We have many other products coming in phase I and II. Most of them, we are looking for partners because they come to areas where we are not focused, and we are in discussion for several of these products with potential partners. Next slide. Last year we announced the results of aprocitentan, and I really like to show this data, which are really very impressive. You see how the two doses of aprocitentan could decrease blood pressure and maintain the blood pressure reduction during the year, which during or eight months, which was asked to be done by the FDA, and where the withdrawal shows the real effect of the drug, because it's really after chronic treatment, it's at the end of the treatment, and you see how the blood pressure is maintained under aprocitentan and comes back with placebo. Next slide. If we looked at ambulatory blood pressure, where there is a much lower placebo effect because it's much more precise, it's done at home, there is no influence of the white coat effect. You see that especially during the night, there is a very significant effect of aprocitentan. You must not forget that these patients were basically treated at least by three antihypertensive medication, but more than 60% were with four medications and some patients were under five or six antihypertensive drugs. Next slide. Aprocitentan has been filed with the FDA and the PDUFA date is in December this year. Janssen will be responsible for commercialization of this product. Selatogrel. Next slide. Selatogrel is a really very innovative product. It's a very short acting and fast acting because it's also given subcutaneously with an auto-injector. It's an anti-aggregant which can be given by the patient himself, who can auto-administer this drug. This should change the approach of the myocardial infarction. Next slide. Because today, patients with such a pain, with a thoracic pain, need to call the emergency unit, the ambulance. It takes on average three to four hours before the patient is treated. Here, just a few minutes after the pain, the patient has been trained to inject himself, then call the emergency unit. You save three or four hours of progression of the myocardial infarction. We know that these are the essential hours which are going to define and determine the future of this patient. Next slide. We are also started the CARE study, which is a study of cenerimod in Lupus with one dose, 2, which has been defined by the phase II and showed a really very significant and meaningful improvement of disease activity with an effect which increased with time and which has been very well characterized, especially which has been shown to be much higher. The treatment effect is much higher in patients with a high interferon gene signature. Of course, we could define the safety of and the good safety profile of cenerimod at this dose. This has allowed us to start the phase III program. Next slide. Where the OPUS 2... The OPUS program, which consists of two trials of each, 420 patients, 210 in placebo, 210 in cenerimod. We have agreed for the design of the study with the FDA. Next slide. As I have described, we are continuing to build momentum in 2023, and we are going to have a higher and broader coverage in the U.S. This is a priority for us for QUVIVIQ. The aprocitentan has been submitted already in Europe. We are waiting for the QUVIVIQ regulatory decision for QUVIVIQ in Canada. As mentioned, the lucerastat is going to be discussed with the regulatory authorities, and the QUVIVIQ will be launched in Switzerland and U.K. The NDA of QUVIVIQ will be submitted in Japan at the end of the year. We will have also the decision for aprocitentan at the end of the year. I hope I have described the really very event full, I think, 2023, which we will have. Thank you very much. Thank you, Jean-Paul. With that, we have come to the end of our prepared remarks and are ready to take your questions. First, a few housekeeping rules, please. May you refer your questions to one only, and then jump back into the queue. Operator, please populate the lines. Thank you. As a reminder, to ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. Please stand by while we compile the Q&A roster. We will take our first question, the question comes from the line of James Gordon from JP Morgan. Please go ahead. Your line is open. Hello, James Gordon from JP Morgan. Thanks for taking the question. I do have one question then, which would be funding. What near-term options are you weighing? Are you potentially considering an equity raise and then to tide you over until later in the year? Are you still optimistic that we could see a partial divestment on Apra Economics? If the latter, what is the trigger that is needed to get it over the line? Might you have to wait for Apra to be approved or the filing accepted? Maybe if I could just squeeze in a clarification, not a question, which is there was talk about a higher stock option expense. Does that explain why there's a bigger difference between core and reported OpEx this year? Should we assume there's something like a CHF 40 million step up in option expense? Thanks, James. Those are actually two questions. Thank you for squeezing that in. André? I follow your rule, Andrew, so I only take the second question. It's easier. James. First question on funding. Well, first, we've always been transparent that we're not funded to break even. With the guidance that we gave at CHF 650 compared to CHF 466 million cash by the end of 2022. Obviously, we need to raise cash and relatively into short term, next few months. We're looking at several possibilities to fund the company. Non-equity dilutive remain our preferred option. I will not tell you where we are into your discussions with potential right monetization investors. Jean-Paul also alluded to a discussion on potential out-licensing deals. Those are two main avenues for non-equity dilutive funding. Saying it's a preferred option does not include, exclude, sorry, equity dilutive. Here it would be equity because I think that a convertible bond would be highly unlikely into your current market conditions. At the end, we really want to remain nimble and we'll remain pragmatic to ensure the business continuity at Idorsia. Your second question regarding, you know, this stock-based compensation. The impact this year, this is valid for 2023, what I describe you. The impact this year is really limited. The rules were clear. Bonuses, except for the executive team, are paid in cash. That sets it for 2022. For 2023, as I said, we change these rules. Where 70% of the bonus across the organization will be paid in shares. Again, there's fight for talent, especially in Switzerland, but also in the U.S. To the extent that we believe that retaining the people with this Ambition 2027, again, look at the governance report, will help us. That's not cash, that's only a P&L impact, and that's why we have it as a reconciliation item between non-GAAP and U.S. GAAP. Thank you, André. Next question, please. Thank you. We will take our next question. The question comes from the line of Harry Sephton from Credit Suisse. Please go ahead. Your line is open. Brilliant. Thank you for taking my question. It's on net pricing for QUVIVIQ. Based on the reported sales and scripts for BELSOMRA, it has a net price of about $150 a month. Is that a good benchmark that we can use for QUVIVIQ, given your reimbursement negotiations with ESI? What proportion of employers have currently opted in for QUVIVIQ coverage? Thank you. Thank you, Harry. Simon, I think that one's for you. Oh, hi, Harry. Yeah, we're not gonna give net price guidance. I mean, clearly right now we're have a lot of drug given away free because of VitaCare as we generate demand and generate co-coverage. I will say, of course, that we priced QUVIVIQ at a premium at the WAC level because of the premium profile that we believe the drug has. It's important for us to continue to try to sort of flow that down as we go through the various different sort of rebate discussions and net conversations that we have. Right now, it's difficult to give you an exact number on coverage in the commercial space, 'cause obviously you've got a number of downstream plans that we're working through. We have a number that are, you know, already in, because as I think I've mentioned to you before, when you launch, you usually end up with something in the order of 20% open coverage for plans that either are not that well controlled or, where they give you sort of a conditional access whilst you're negotiating. I think our broad estimate right now is that we're probably somewhere in the sort of mid-40s in terms of commercial coverage, and that we would expect to start to move that up into the, to the 50s as we start to bring through the downstreams that I referenced with ESI, when we get into sort of Q2. Thank you, Simon. Thank you, Harry. Operator, next question, please. Thank you. We will take our next question. Our next question comes from the line of Rosie Turner from Jefferies. Please go ahead. Your line is open. Hi, thank you for taking my question. I'll jump back in the queue after this one. Yeah, just lucerastat, that long-term extension study, did I hear, just towards the end of the call that that is being discussed with authorities? I think we saw on the FDA website it's been extended out further. Is there something going on there? Is it something that could we should potentially be thinking about adding back into numbers? Thank you. Thank you, Rosie. Jean-Paul, do you wanna comment on what we're thinking? No, I think we have been waiting really to get two years data on the renal effect of lucerastat, which are, in my mind, quite impressive. We have also measured a subgroup, some very specific subgroup of patients. I do not want to give competitive information. You know, we need to discuss with both Europe and the U.S. in order to really see where we can go. It's very clear that the drug is active, this is a regulatory issue. Thank you, Jean-Paul. Yeah. Just very quickly, Rosie. Yes, that observation is correct. The open label extension was extended from 48 months out to. Six years. Six years. Given that the first patients were actually reaching that four-year mark. Perfect. Thank you. Thank you, Rosie. Operator, next question. Thank you. We will take our next question. Our next question comes from the line of Thibault Boutherin from Morgan Stanley. Please go ahead. Your line is open. Yes, thank you for taking my question. On QUVIVIQ sales expectations for this year, you know, when we look at your guidance, it looks like you're expecting roughly CHF 100 million for QUVIVIQ globally. If you could just help us understand the split that you expect broadly between U.S. and ex-U.S. Second, I mean, you know, follow up on this. In the U.S. Dynamics for QUVIVIQ, right now, BELSOMRA is annualizing around $80 million a year in the U.S. If you could help us understand the dynamics for QUVIVIQ in the U.S. in terms of, I guess one side is prescription growth, the other side is transition to paying prescriptions. If you could help us how we should... How you're kind of thinking about this through the year and basically, does this mean that the vast majority of sales for QUVIVIQ this year should be kind of back-end loaded towards the end of the year? Thank you very much. Thank you, Thibault. I can take it. Good point. Yeah. I can take those parts. Thibault, I would like to help you, but I'm not sure I will be able to do so. Just for the latter for your second question. Yeah, it's more skewed to the end of the year because here, as Simon said, well, we believe that we'll drive higher volumes week after week and that we see a pace coverage, these volumes will convert into net sales. Yes, clearly there's a higher amount in Q4 and in Q3 compared to Q2 or Q1. That's one. On the other side, having a breakdown of net revenue, i.e., sales, and contract revenue, the only thing I can tell you is that in the contract, revenue, we do not speculate on new out licensing deals. We have a few involved in the air. We, it's like M&A, you need to be two. We have not factored here any additional contract revenue. You can reasonably expect that the it's mainly driven to CHF 230 million, mainly driven by sales. PIVLAZ you've seen, the trajectory quarter-over-quarter. Where PIVLAZ has a significant amount, but the biggest one is QUVIVIQ in the U.S. Okay. Thank you, André. Before handing over to Simon to give some clarifying points on how his views are on BELSOMRA, we're not guiding on product specific. The consensus right now that resides on our website calls for CHF 110 million of QUVIVIQ sales and CHF 95 million of PIVLAZ sales. I feel comfortable with those numbers being out there in current consensus. Simon, do you wanna make some comments on BELSOMRA and where that stands right now in terms of its numbers, and how did that compare? I mean, I think as I showed in the presentation, we're close to being through on MBRXs. I think we'll be through on TRXs in the next few months. We'll be in a position where we're driving more volume than BELSOMRA in the next few months, I'm sure. As André said, it's really now about pulling the payer coverage through to convert that volume into net sales. I mean, I think really you end up with several benefits of payer coverage. You end up obviously converting free scripts to paid scripts and that generates net sales. It also removes the NDC blocks that are in place when payers are blocking you. That allows currently written scripts to start to move. Also, we know from our research that the lack of coverage is certainly a disincentive for doctors to write more. I think that obviously with our sales force activity and now that we've got the coverage, we will expect to see demand grow as a result of this. I think that the payer access for sure has a net sales benefit obviously, but it also plays an important role in demand generation as well. I think we would expect both of those things to collectively play through the next year. As André said, that will build over time, which means that we're more back-end loaded than front-end. That's very helpful. Thank you very much. sorry, just on the second part quickly. From what, from your answer, we can infer that the vast majority of QUVIVIQ sales you're expecting are going to be in the U.S. in 2023? The majority are. U.S. accounts are the majority, yes. I will not quote how much vast means, but the majority is U.S. clearly, yes. Okay. Thank you very much. Thank you, Thibault. Operator, next question. Thank you. Once again, if you do wish to ask a question, please press star one and one on your telephone. We will take our next question. The question comes from the line of Rajan Sharma from Goldman Sachs. Please go ahead. Your line is open. Hi. Thanks for the question. Just had one on PIVLAZ. I think you talked about, penetration at 25% in December, which looks flat compared to November, as you updated in January. Can you just talk about, how you see penetration evolving from here, given that you're at 95% of target accounts? Thanks. Yes. Sure, Rajan. Yeah, sure. I mean, I think I've said in previous calls that we absolutely expected a pretty rapid ramp, and then that curve is gonna start to slow down. I mean, I think you often see that with specialty drugs, but we're certainly seeing it with PIVLAZ because what we've seen is the trial sites and the investigators jump in very quickly, which is what's given us this sort of rather rapid uptake as we've seen in the first sort of eight or nine months. I think you'll now start to see that the increase will be more modest each time we come through quarter on quarter. I expect it to grow. I just don't. We shouldn't expect to sort of, I think I said this at Q3, we shouldn't expect it to be linear. We're gonna be at 100% market share by the summer if we go on at that rate. We really are expecting to continue to see growth, but I think it'll become now more modest as we move into the rest of the market and people who have less experience with the drug and will perhaps move a little bit more slowly than the investigators. Thank you, Simon. Operator, do we still have questions? Yes, we do. One moment, please. Please stand by. Apologies for the delay. One moment, please. Your question comes from the line of Sushila Hernandez. Please ask your question. Hello. Thank you for taking my question. I just have a question on your early stage pipeline. You already briefly touched upon it. What is your strategy here, and what is your priority here? Thank you. Jean-Paul, what's the, our strategy on the early stage pipeline? I, the early stage pipeline, we have discovered, you know, we have profited of many projects which really have come to breakthrough. We are really focusing only on specialty products, you know, very, very, because these are our choice. You know, we now have that, the possibility to do research on a very selective topic. First is specialty product, very limited orphan drugs and high medical need, most first in class, sometimes best in class. I would say nearly 90% first in class with very significant breakthrough. As you know, these are in compounds in phase I, in phase II, and there is always, you know, not a 100% sure that they will make it to the end. This is why we look for partners like we have done with Neurocrine, where, you know, these are, they are working with our T-type calcium channel because they are really a CNS, very specialized company. We try to do the same for many of these early projects. We will keep the development for maybe one or two, but most of these products should be partner. Thank you, Jean-Paul. Thank you, Sushila. Operator, do we have more questions? Thank you. One moment, please. We will take our next question. The question comes from the line of Jo Walton from Credit Suisse. Please ask your question. I just wonder if you could tell us a little bit more about your response to the REACT study, when you'll make a final decision, how long it should take, and is there any write-off at all if you decide not to take the product outside of Japan? Please just confirm, you will be taking that data to Japan to the regulators, but presumably you are confident that there will be no change in the trajectory of PIVLAZ adoption in Japan post the ex-U.S., sorry, the ex-Japan data. Yeah. It is true. You know, this is, as I mentioned, a different dose, different conditions, different administration mode. I think this is really a very different study. Of course, we are analyzing the data, but with a negative primary endpoint, it's, you can assume that we will not file it neither in Europe or U.S. I think it's better now to really concentrate on Japan and concentrate on other projects. That's, that's, yeah, the unfortunately the end of clazosentan for U.S. and Europe. Are there any kind of financial consequences, André? No. There's no financial consequences. You know, we, as I said, we only plan for what we know. To this extent, I was not planning anything regarding REACT filing in the U.S. or Europe or additional costs in connection with the pre-launch activities. There was no change in the guidance that we gave, and because there's no impact of clazo beyond the ongoing commercial execution in Japan. Okay. Thank you, André. We've come to the top of the hour. Operator, do we still have any questions in the roster? There are no further questions. Okay. Well, thank you very much, Heidi. We've come to the end of our webcast. Thank you very much for your ongoing support of Idorsia. Operator, please close the lines. This concludes today's conference call. Thank you for participating. You may now disconnect.