Thank you, Heidi. Good morning, good afternoon, everyone.

My name is Andrew Weiss. I'm the Head of Investor Relations and Corporate Communications here at Idorsia.

With me on the call today to discuss our full-year results and our outlook for the future are our CEO, Jean-Paul Clozel, our CFO, André Muller, and our Chief Commercial Officer, Simon Jose. With that, I think we're ready to kick it off with our prepared remarks.

Next slide. In this call, we will be making forward-looking statements.

Hence, you have been adequately warned about the risks and benefits of investing in Idorsia shares. Next slide.

Jean-Paul, the floor is yours.

Thank you, Andrew. And I am very happy to really discuss what we have achieved in '21, and how is the outlook for '22 and the years to come.

First, the big picture. In Idorsia, we have a common vision, the management and the collaborators want to create a sustainable, mid-size pharma company, which is based on innovation, makes that.

And from day one, which means about four and a half year ago, we had defined five key strategic priorities. We wanted to 1.

deliver three products to the market, 2. build a world-class commercial organization,3.

bring Idorsia to sustainable profitability, 4. fuel our pipeline with new discoveries and 5.

utilize state-of-the-art technology to drive innovation. Next slide.

2021 as I mentioned, was a very strong year for what we have achieved and executed. We entered and closed 2021 with a strong balance sheet thanks to money raised that we could achieve, and Andre will discuss this fact.

We find the daridorexant in the different in the world. And we received -- Johnson & Johnson received our approval for Ponesimod, an S1P1 drug that was discovered in Actelion and -- which was developed by our team for the larger part.

We filed clazosentan in Japan, that was all at the beginning of the year, started the Phase 3 of selatogrel. And at the end of the year, we got the results for Lucerastat for cenerimod.

And last but not least, this year and -- beginning of this year, thanks to all this work, we've got PIVLAZ approved in Japan, clazosentan approved in Japan, and QUVIVIQ approved in the United States. Next slide.

So first goal was to deliver three products to the market. So we are in good track, daridorexant, clazosentan - approved.

I think that aprocitentan will give results middle of this year and many other growth. As you can see, our eyes are in late-phase development or in Phase two to this goal, I think it's achievable within a short amount of time.

Next slide. So last year we obtained the result for lucerastat.

Of course, we were disappointed by the fact that we couldn't show an effect on neuropathic pain, but we have seen very interesting other efficacy signal, which really encouraged us to continue the open-label phase of this study and to discuss with the authorities in view of the very strong effect, for example, on biochemical markers. and on some function for the patients, like the renal function.

For cenerimod, we have with our Phase 2b, good information we needed in terms of which is the dose, what is the efficacy, what are the safety, and what is the optimal endpoint. So therefore, we are advancing cenerimod in Phase 3, and we are discussing the program with the regulatory authorities, especially the FDA.

We -- for our aprocitentan patients are all recruited, we are doing -- performing the study. We should have the results in the middle of this year.

And I'm really very optimistic for this drug since the safety looks really good and we have a clear, I think signal also of efficacy. Then selatogrel, as I mentioned, as under an SPA started the Phase 3 and for our selective orexin receptor antagonist, we have finished recruitment and we should have the results of binge eating in second quarter of 2022 this year Next slide.

So of course, daridorexant has been the big news beginning of this year, and it's really going to be a global product. It has been approved in the U.S.

We have five-year market authorization in Canada, and we are waiting, I would say in a months or weeks the authorization by the European Medical Agency, and also we are waiting for the answer of Swissmedic. And the Phase 3 is ongoing in Japan, and hopefully will be finished this year.

Next slide. So the results of daridorexant two studies, two Phase 3 studies have been published in The Lancet Neurology.

That's really -- the results, as I said, is one of the nicest set of results I have seen in my career. Next slide.

Because [Indiscernible] the drug was working to really improve or decrease of time to fall asleep, but also to stay asleep and the [Indiscernible], which is a time that people are waking up after falling asleep during the night. So this is a time that you want to decrease, which is increasing in [Indiscernible].

And as you can see you have a very nice dose response effect on [Indiscernible] Next slide. But also on time -- or the time to fall asleep, which is called Latency to Persistent Sleep.

So you sleep faster, you sleep longer. Next slide.

And if you ask, which is quite unique, I have to say, if you ask the patients how long they are feeling they have slept, you see also that subjectively, they have -- they feel that they have slept longer. And this is highly statistically significant, especially with high dose of, I would say not -- should not be the high dose, with the dose of 50 milligrams, which is the right dose, not the high dose.

Next slide. So very important evaluation we did in this program was to ask with patient reported outcome questionnaire, we have evaluated what does the consequences of this improvement of sleep on the day performance.

First domain, because we have group in Suite domain, this functioning was released what we call the sleepiness domain, and you can see the question was, how the four main questions of this domain was asking the patient how they feel energetic, mentally tired, physically tired or sleepy during the day. And as you can see, you have an improvement which means a decrease of this domain score.

And especially with a 50 milligram, you'll have a very significant, the p value is, as you say, it's very low. A very significant effect on this sleepiness domain with daridorexant.

Next slide. And even more interesting in my mind is the fact that the other domain about mood, about cognition alertness.

how people memorize how they feel that they can memorize event. This was also improved, this was exploratory endpoints, but very clear results.

Next slide. You could really -- and that was a big question with such a fantastic effect during the night and during the day, is there a side effect which prevent -- especially with the 50 milligram, prevent the use of these higher dose?

And as you can see, that has been really -- and this is absolutely unique to this product. You see that if you take, for example, the somnolence, the 50 milligrams, there is less somnolence in the morning, as with 25-milligram of daridorexant and about the same level as placebo.

So by giving the dose of 50 milligram, you do not have a price to pay by being groggy in the morning. And that's absolutely fantastic, and that has been recognized in our label, or U.S.

label by the fact that there is no recommendation of a dose titration, P-patients can be treated by 50 and should be treated by 50 milligrams. Unless, as there is a special case like, for example, the liver problem, then the 25-milligram in this specific patient should be given.

So a very, very, very good safety profile. Next slide.

So I'm going to give -- we such. First of all, I'm going to give to the commercial organization of Idorsia, this fantastic drug, and Simon is going to tell us and to tell you how we are going to commercialize daridorexant.

And of course, also clazosentan, which as I've mentioned, has been approved in Japan. So please, Simon.

Thank you. Jean-Paul.

And good morning, and good afternoon everyone. The next slide, please.

So obviously, as it has been said, our second strategic imperative is to build a world-class commercial organization. And we're focused on two priorities to achieve this: the first is to establish a commercial footprint with the right people, infrastructure, and processes needed to successfully launch our new products.

We've built teams of outstanding people, along with simple and consistent structures and processes, which enables fast decision-making and allows us to remain nimble. And of course, whilst we've been doing this, we've also been developing our ambitious launch plans for QUVIVIQ in the US and for PIVLAZ in Japan, which I will expand on in the next few minutes.

As the metaphor goes, we really have truly been building the plane as we've been flying it. And it's an exciting time for us now as we start to execute our plans.

I'm confident that we're very well prepared to deliver successful launches that will exceed expectations. Next slide, please.

I'll turn now to the insomnia market and the launch of QUVIVIQ in the U.S. Now the U.S.

insomnia market is huge, we -- there's an estimated 25 million people suffering from insomnia, about half of whom are treated with a prescription medicine. In a large survey of Americans with trouble sleeping that we sponsored, 70% of respondents said they were desperate to find a solution addresses the impacts of insomnia on both the night and the day.

And simply too many patients are currently cycling through prescription medicines, over-the-counter treatments, without finding the solutions that they need. And obviously in addition to the impact on patients ' lives, insomnia has a significant economic burden in the US, which is estimated to cost more than $100 billion a year.

Next slide, please. If we look at the prescription market, we see in the last decade, there has been a significant shift away from the ZED drugs in favor of trazodone, an antidepressant, which is not licensed for use in insomnia.

Now trazodone is now the most widely prescribed medicine for insomnia in the U.S. So physician preference to use an off-target effect of an unlicensed product in favor of licensed medicines is a reflection of the limitations of existing treatments, and further highlights the significant unmet need in the market.

Next slide, please. And obviously as you all well-aware, we received FDA approval for QUVIVIQ on January the 7th.

We are planning to launch in early May after the DEA scheduling process is completed. Next slide, please.

Now, in many calls that we have with investors and analysts, we're often asked how Idorsia, a relatively new startup, can be successful at launching a primary care product. Now for me there were three critical factors that will drive our success and which make us different.

A differentiated product, a handpicked and focus team, and the right go-to-market approach. And I'll expand on each of these in turn.

Next slide, please. As you've heard from Jean-Paul, we do have an outstanding dataset from a robust clinical trial program and a differentiated label for QUVIVIQ.

QUVIVIQ helps patients to fall asleep faster and stay asleep longer. But this of course is really the entry ticket in this market.

So in addition to this, QUVIVIQ 50 milligram, which was evaluated in one of the two pivotal trials, demonstrated a significant improvement in daytime performance with a validated if sick patient reported outcome instruments as Jean-Paul has just shown you. But perhaps most importantly of all, in this market, QUVIVIQ had a favorable AE profile.

There was no evidence of tolerance or dependence. And as Jean-Paul showed you, the rate of somnolence or fatigue similar between doses and only 1% greater than placebo for the 50 milligram or in 2% greater than placebo for the 25 milligram.

There is no recommended starting dose or requirement for dose titration, unlike other products in the class. And based on the efficacy and safety profile demonstrated in our pivotal program, we believe that 50 milligrams will be the right dose for most patients.

Next slide, please. I'm in the US at the moment, with our team and continue to be impressed with the caliber of talent we have recruited into the organization.

Our U.S. leadership team has been hand-picked for their launch experience.

And their desire to transform a market and build a business. They are all really experienced commercial leaders from different companies and backgrounds who collectively have executed 74 launches.

But just as importantly, the team is completely dedicated and focused on the launch of QUVIVIQ. Rarely, will you see a team of people with this level of experience and seniority working on one -- just one product.

And this makes a huge difference, trust me. Next slide, please.

So turning to the commercial approach and our go-to-market strategy. We've developed a highly consumer - centric strategy to launch QUVIVIQ in the U.S.

And by that I mean that we're putting the consumer and consumer activation at the center of what we're doing. Physicians and payers are of course critical, but we believe insomnia can be consumer-led given the nature of the condition and the deep dissatisfaction patients are currently feeling.

The U.S. team has already launched two educational initiatives to raise awareness of insomnia, and the significant impact it has on people's lives.

First, the sleep -- The Alliance for Sleep brings together some of the foremost experts in sleep medicine to drive education, awareness, and research on the burden of sleep. Second, and you've hopefully all seen our new Seize the Night & Day campaign.

This education and awareness campaign highlights the need for the night and the day impact of insomnia on patients and their families. And we're thrilled to be collaborating with Jennifer Aniston on this unique consumer-focused campaign.

Additionally, we have supported the Wake Up America survey, which is the largest U.S. survey of both people with trouble sleeping and of healthcare professionals.

The results will be published in the coming weeks. The US team has also produced a documentary called The Quest for Sleep.

And this film highlights real people suffering with insomnia and provides a look at the science of sleep. And this is set to premiere in March.

Next slide, please. Now, there are strategies centered on the consumer, as I just mentioned.

It is critical we pull through effectively with physicians and payers. The U.S.

sales force is now being recruited and is currently being trained. And to support the sales team, we have invested in advanced analytics to enable precise customer targeting and engagement.

The best example of this I can give you is the next best action for our sales team, and maybe for those of you that are familiar with using ways for driving, this is a similar concept, where we're using advanced analytics to define optimal actions in real-time and what the right sequence is. And this will be available to support the sales team when they start engaging with customers.

Our excellent payer team has been engaging with payers for several months now, introducing the company and discussing insomnia. Following FDA approval, they are now meeting payers to discuss QUVIVIQ and our clinical data.

And finally, for the past year, the medical team has been engaging with insomnia experts across the country. So in summary, I'm confident that with our differentiated product, a talented and focused team, and our innovative go-to-market approach, we are well-positioned to transform the insomnia market and successfully launch QUVIVIQ in the U.S.

Next slide, please. So two weeks after the approval of QUVIVIQ in the U.S., we, of course, received approval of PIVLAZ in Japan.

I believe this launch is also going to be a significant opportunity for Idorsia. And I'll touch on the reasons why next.

Next slide please. Now if you could pick one market for the first launch of this product, it would be Japan.

The incidence of aneurysmal subarachnoid hemorrhage or a SAH in Japan is three times higher than it is in the rest of the world, with an estimated 30 thousand cases per year in Japan. There was a high degree of anticipation amongst neurosurgeons for the launch of PIVLAZ.

W ith no new products to help prevent vasospasm following aSAH in over 25 years, the introduction of an innovative new treatment option is long overdue. And finally, many of you will be familiar with a significant burden and long-term consequences of vasospasm.

The physical and cognitive deficit, the social and emotional consequences, and of course, the healthcare costs. Next slide, please.

Our team in Japan is very well prepared now for the launch of PIVLAZ, which we expect in early quarter two, whilst this is a very different go-to-market model than QUVIVIQ in the U.S., being a highly specialized product in hospitals, I believe we have the same three key ingredients for success, an innovative product, a highly experienced team, and the right, focused launch plan. Our MSL team was deployed in the middle of last year, and has been engaging with the leading medical experts and neurosurgeons since that time.

Our specialized sales team was deployed right after approval in January. The team is now talking to physicians and 650 target hospitals about the process to formal listings.

So that when we do receive the price in early quarter two, we can launch very quickly. So in closing, we are absolutely ready for the immense opportunity we have in front of us to launch two innovative products in two of the world's biggest markets within what could be weeks of each other.

We're fully focused on making both these launches successful and fueling the growth of Idorsia for many years to come. With that, I'd like to thank you and I'll hand over to Andre.

Thanks, Simon. Hi, everyone.

Greetings from motorhome, not for your famous mountain Swiss alps, but a meeting room here in Radnor at our U.S. headquarter.

As Simon has said, it's good to meet with our U.S. colleagues face-to-face, and getting a fully annotized by your team.

Next slide, please. Jean-Paul mentioned our key five priorities.

Let me walk you through the third pillar of our strategic priorities. We have a dual model with -- on one side, having net sales from the approved portfolio, or hopefully to be approved.

As the first one in -- Simon walk you through with of course, daridorexant in the U.S. Soon coming in Europe, and hopefully, depending on the results of the ongoing Phase 3 trial in Japan, adding also in Japan.

We have of course, clazosentan in Japan. And we may add clazosentan in other territories, depending on the result of the REACT trial.

And depending on the interaction, we see regulatory bodies, we could have also lucerastat. Later on, beyond 2025, we said two Phase 3 ongoing, we could add cenerimod and selatogrel.

On [Indiscernible], we also have [Indiscernible] and royalty streams, starting with Ponesimod launch by J&J in the U.S. and European countries, and also Canada.

Hopefully as Jean-Paul said, with a positive readout in mid-2022, aprocitentan and here will piggyback on the success of J&J. Most of you may have seen in our business updates last year, I think it was in November, that aprocitentan was one of your 14 compounds where J&J see a blockbuster potential.

We have also see T-type calcium channel blocker out-licensed to Neurocrine. And we could get some positive news -- hopefully positive news from two ongoing Phase 2.

One in essential tremor and the second one in some rare form of epilepsy with children. And lastly, we have [Indiscernible] River Heather and the deals that were also signed to some tail.

Next slide, please. Let me walk you through the full-year results of 2021.

If we start on the left side, we have a revenue software CHF35 million. This is relating to collaboration entered into in previous years.

See a non-GAAP operating expenses at CHF612 million, as expected are in line or -- in line with Q3 again, so which was slightly below CHF620 million, leading to a non-GAAP operating result of minus CHF576 million. Adding the D&A and share-based compensation, we ended up with U.S.

GAAP operating loss of CHF613 million. Below EBIT, the CHF22 million is mainly relating to the accretion expenses that we had in connection with convertible loan from Cilag i.e., J&J.

So you know, we're in Q4, Cilag decided to convert the second trench of CHF110 million, and this led to a higher accretion expense in Q4 2022. With this, we close the 2021 financial year with a net loss U.S.

GAAP of CHF635 million. Next slide, please.

If we have a closer look to see non-GAAP operating expenses, you see an increase in development, excluding the inventory builds. As you know, before drug is approved, the inventory build goes directly to the P&L, which will no longer be the case for daridorexant and clazosentan moving forward.

But we had increase -- an increase in development. You see the CHF250 million.

Actually the increase was mainly due to the initiation of the Phase 3 of Selatogrel, not so much on the clinical development side, but with also work relating to a drug substance and drug product. And we also invested more in the early stage of pipeline because this one is also advancing relatively fast.

The SG&A, you see here that we had the biggest increase with CHF221 million breaking down in 144 in marketing and selling compared to 27, that's exactly a relating to what Simon explain, preparing for year launches mainly into U.S. also in Japan, and to lesser extent in UK and in Europe.

And we had also a slight increase in G&A, with CHF77 million compared to CHF63 million in the previous year. So with all these numbers, we ended up with non-GAAP operating expenses CHF612 million.

Next slide, please. Cash flow and liquidity, which includes cash equivalents, and also short or longer-term deposits.

As you can see, we ended the year with a strong balance sheet, CHF1,188 million liquidity. So fundamentally, same level slightly below CHF12 million or below the start of the year 2020.

And that's mainly due to the issuance of our convertible bond in July 2021 for net amount of CHF595 million, which fundamentally offset via the non-GAAP operating expenses. Next slide, please.

Here is the guidance for 2022. Net sales of CHF120 million.

Contract revenue of CHF25 million, and that only relating to what we know, i.e. some deferred revenue from previous collaboration and the revenue sharing on [Indiscernible].

So I'm not speculating -- we are not speculating on any other revenue milestone, notably, in connection with Neurocrine or with some tail. SG&A would increase to CHF520 million, that's the cost to launch a drug in a primary care setting, and R&D would be more or less stable with CHF400 million.

So we would have our non-GAAP operating loss around CHF785 million for the full year, 2022. As the difference between non-GAAP and U.S.

GAAP is mainly relating to a DNA and share-based compensation. Around CHF55 million split evenly between SBC and G&A.

Next slide, please. Contrary to see our previous years, we wanted to also -- if you -- what is clear objective for us are the profitability target.

We strongly believe that we can become profitable by year 2025 with annual net sales set to would cross year CHF1 billion mark. And I trust to give you some context here, we see the goal.

It is only based -- we see a portfolio, which is approved, so daridorexant into U.S., or on the verge to be approved in Europe, Canada, and Switzerland, where we are highly confident to get market approval. So we will launch in Germany, Italy, UK, Switzerland in a staggered approach.

Same for France, Spain, and Canada. And we also only add clazosentan in Japan.

So we're not speculating on the ongoing Phase 3 in Japan, which is currently conducted by our local affiliates and Mochida, our partner. We're not speculating on positive results of the REACT trial, hopefully by the end of this year 2022.

So we are really counting on the existing scope and anything that would come on top and above, we mentioned, of course aprocitentan we see a tiered royalty. We would be entitled to in connection, we see a launch by your change eight or any milestone coming from Neurocrine a neural cream, or from Mochida in connection with the see positive results of Phase 3 in Japan or even Santhera, is in the -- is not in the scope.

We this year -- pass the baton to Jean-Paul, who will tell you more about the fourth and fifth pillars of our strategic priorities. Jean -Paul.

Yes. Thank you, Andre.

Thank you very much. And for this clear outlook, and towards profitability.

So of course, profitably -- to reach profitability is important. It was also important for us to continue to beat the buy time, because as you know, a company only can survive if it can really launch new products, because after 14, 15 years compounds become generic.

And we count on organic chemistry to discover these drugs, and this is a priority we have. And of course, we are not developing for the time being antibodies, new technology.

[Indiscernible] We are focusing on small molecules. And this is due to the fact that we have top chemists really trained in Switzerland where -- which has some of the best schools of chemistry, and the advantage of these small molecules is that of course you do not have a technical risk like you have for some new technologies, like gene therapy, like gene editing, where you still have a significant risk, technological risk.

Here, these are our methods which are well-known and which are adapted for chronic and also acute diseases. They can be very often given as a pill for oral use or a capsule, and they have a clear pattern protection.

You are not in the fight like you have in some of the new technologies. And of course, we can really try to optimize the output of this chemistry discovery efforts by using not on the high-throughput screening but Artificial Intelligence, computer Modeling, really trying to have all the new technologies adapted to organic chemistry.

Next slide. Number five was really not to do the same thing as we were doing in Actelion, but we had to utilize state-of-the-art technologies to drive innovation, which means, in our mind to really continuing to implement this new technology, not only for drug discovery, I've mentioned Artificial Intelligence Computer Modeling, but also in clinical development where we are working with technologies.

Also with artificial intelligence, where they're all federated learning, and so on. But also for commercialization, just as Simon has mentioned, how we have implemented the technologies to really optimize the use of the time of our medical representative, how we can really adapt to the market using some new software, new technologies specialized for optimizing commercialization of our products.

Next slide. So 2022 will be the year where we are going to become -- Idorsia is going to become a commercial company.

We, after the approval of QUVIVIQ in Japan and U.S. And hopefully soon in Europe, we are going to launch Q2 -- beginning of Q2, 2022, Clazosentan in Japan.

And in May, QUVIVIQ in U.S. And at the end of this year, we are going to QUVIVIQ in Europe.

Next slide. But 2022 will not be only the year of commercialization or becoming a commercial company, it's also a year where we are going to get key results.

Precision with aprocitentan, mid of this year. BGting, with our selective orexin receptor antagonist [Indiscernible] will start the Phase 3 in lupus and we are very hopefully, and I think there are good chances that we conclude the Phase 3 study REACT of Clazosentan, if there is not another COVID major crisis, which I think seems unlikely.

A very, very busy year and as we have mentioned, there is a lot of optionalities because we are not including in our guidance for profitability the revenue of aprocitentan, or of [Indiscernible] or cenerimod or clazosentan. All these products will add to and fuel -- sorry, will increase our growth, our rate of growth.

And are just potential addition to our curve of growth. Next slide.

So frankly, if you would have asked me, when we started Idorsia, that within five-years, you could launch two products in the main countries, becoming a fully fledged biopharmaceutical company, including presence in Japan, in Europe, in U.S. And with a clear view of when we can reach profitability, I think I would have told you, I'm ready to sign because that's not -- that's very few precedence in the biotechnology world with such a rapid growth and the establishment of a new company.

Thank you very much. And that's -- we can finish on this profitability goal.

And I think that, Andrew, I leave the floor to you.

Thank you, Jean-Paul. Next slide, please.

So with that, we've come to the end of our concluding -- to the end of our prepared remarks, and are ready to take your questions at this point in time. We've got two formats, oral as well as written formats, so I'll let the operator open up the question rosters now.

Thank you. I'm Peter Verdult, Citi, three quick questions, please.

Firstly, for Jean-Paul or Andre, share price reactions today seems to signal expectations Idorsia will tap the markets again this year. Just wanted to hear your thoughts there versus monetizing the [Indiscernible] potential [Indiscernible] royalty stream.

Secondly, on aprocitentan and Jean Paul, just wanted to kick the ties given we got Phase 3 data, middle of the year, we know what the FDA wants to see in terms of efficacy. The [Indiscernible] feedback generally positive.

We're going to see edema, but as long as it's tolerable. The drug is of great interest.

So with respect to this -- edema angle, which seems to be the potential. But on a scale, how comfortable are you that the edema profile for outgrow is tolerable.

And then lastly, Simon on QUVIVIQ. You probably don't want to go there, but I'll try anyway.

Any ballpark quantification of the U.S. price point that you'll be seeking?

How aggressive or not you intend to be it with couponing and the size of your commercial team with respect to the Salesforce at launched? Thank you.

Thank you, Peter. So, yes, you've addressed the questions directly.

I would suggest the capital markets question to Andre, what are your thoughts right now on how our abilities of liquidity. On the edema, I would give this directly to Jean-Paul and pricing or more, where are we right now with our negotiation strategies, with the different payer accounts to Simon.

Peter, I can start with your first question. You mentioned equity raise.

I would say without any cash raise, we see a guidance -- we would end 2022 with approximately CHF400 million. So this could be acceptable but of course, if we have any opportunity at the right price to raise cash, not necessarily through equity, but cash, we would do so.

I mentioned in the past that we have different avenues to do it, right now, we see our current stock price, I don't think that equity would be a favored route by far. Convertible as well, even if you would mitigate, sees a lower stock price.

We see a conversion premium. So we are much more inclined to explore potential revenues, we use the royalty monetization deals, you you mentioned PONVORY.

We could also add aprocitentan. The best to monetize aprocitentan is to get the results, and as Jean-Paul said, for different reasons, efficacy and safety, we believe it could be positive.

And we have also -- we see a rich pipeline, potential out-licensing deals. So just to be very clear, we are much more working now on these last two avenues, royalty monetization and out-licensing deals.

Thank you, Andre. Jean-Paul, on odema and your thoughts [Indiscernible]?

Yes. I think that -- you have to know that daridorexant -- I'm sorry to start to with daridorexant.

Daridorexant was the ultimate orexin receptor mixed on antagonist. It took us 25 years to really discover this drug.

And it was a very, very big effort. Aprocitentan is the same.

It's the ultimate, mixed undertaking receptor antagonist. It is work -- now, it's more 30 years that Martin started to work on this dream project.

And really we came with a product which is by nature mixed blocking both receptor. And we believe that because also of the fact that he has a very specific pharmacokinetics, not being influenced by renal function too much.

It is really the ideal drug for resistant hypertension. And it should be having much less than edema than other selective blocking on the ETA receptor antagonists, which most of the time have been tested in clinical trials.

So first there is a rational way should have an edema. Now we have treated more than 800 patients for nearly a year or nine or eight months for most of them.

We have got seven DSMB which have not mentioned any issue. We have not seen a very -- a clinically, I would say significant edema problem, and this had not been mentioned because we are still blinded.

It has not been mentioned to us, by the DSMB. And what is very important is that what we see on the opposite is really a signal.

And for eight months during the trial, the patients are in the open phase. So we know they are treated by 25 milligram, the highest dose of Aprocitentan.

And we see a very, very significant and marked blood pressure decrease. And I just cannot wait to see the results of this study because I think people are going to be surprised by the efficacy in resistant patients.

This is very severe patients. You are going to see not only a very good safety, but a fantastic efficacy.

That was clear. Jean-Paul, Simon, do you want to take the question on dari, and where we are with QUVIVIQ negotiations?

Yes. Sure.

And I'll take the three questions in turn. In terms of price, the payers we know we'll start with the BELSOMRA price as their starting point.

But given the profile of our product, we're looking at a premium to that. Obviously won't be disclosing anything more specific than that, but we believe that we have a superior product and we will price for that value off the back of the current prices of BELSOMRA, which is just over $400 whack a month at the moment.

We will be couponing, yes, I mean, obviously while we build commercial access we'll want to have patients try the product. And actually we do see quite a benefit there, because we know that successful trial use is going to be critical with this product.

And I think for people to be able to use it, and use it for an extended period through a coupon in the script will be very beneficial to them. And to the continued use.

And in terms of sales force, we're going to be in the 400 to 500 range. Just to give you a sort of guidance on that.

Thanks. You were very helpful.

Thank you.

Thank you, Peter. Operator, next question, please.

Sachin Jain here, I'll will take a couple of [Indiscernible] and then a couple of financials if I may. Firstly, on daridorexant and just a couple of commercial questions.

How does being a scheduled drug impact your consumer driven focus of your marketing strategy and focus on PCPs versus specialists. Just wonder if that's creating any specific hurdles that you are navigating.

And then on positioning, you clearly referenced a Question Noise That drugs on a launch. Just wondering on your positioning versus CBT, which in times become, I think preferred first-line therapy.

And then on financials, the 25 garner being profitable versus greater than a billion in sales, I guess, implies a flattish cost base from the 22 levels. 2022 costs are essentially double what they were two years ago, so just wanted to make sure I interpreted that correctly.

And then last question on financing just wanted to clarify comments. You noted a lack of equity or it was really a function of the share price.

If the share price responses to a successful Daridorexant launch, would equity be back on the table or are you talking ruling that out? And just as you think about royalty or out-licensing, whatever what timing are you thinking through, it sounds like 2H?

Thank you.

Thank you, Sachin. So I'll probably give the first question to Simon, second question to André.

Yes. So I'll take the first couple.

Such -- I don't think we see scheduling as being a particular issue or barrier to our DTC activities. We obviously have to be clear in all of our promotion whether it's to healthcare professionals or to patients to this Schedule four, which is what we expect.

But that's the same with every other sleep drugs. So we don't see that as being a barrier and there's nothing specific in the regulations that mean you have to do DTC in a different way if you were a scheduled drug, other than the fact that we need to be clear that we are scheduled.

So that is fine, I think. Regarding CBT, honestly, I don't think we really see that as a competition.

I think, we're competing in the full prescription market and which is in the U.S. alone is 75 million prescriptions.

CBT is variably effective and certainly is not widely accessible. So even though there obviously is a bit of momentum at the moment with CBT and apps and digital and so on, so forth.

And it may grow some, I don't think we see it necessarily as anything that we would compete with will. We'll take the prescription competition that comes after that, which is still a very significant opportunity, particularly when you start pulling in a lot of the OTC medicines that people are cycling through.

So although we can look at a 75 million script market. I think when you stop putting the OTC medicines and it gets larger than that.

So we're not intending to really reference or go after CBT. It's all in the -- the post CBT prescription market.

Many people that don't get to go through CBT anyway, because it's just not accessible or in some cases, it's not recommended.

Yes. Hi, Sachin.

Regarding your -- maybe second question regarding funding. Never say never or not rule it out to a top equity capital markets, but sets -- I would say unlikely false year time being.

And again, we're not against the wall. So we'll still closely monitor, the equity or equity-linked capital markets, but we have a clear preference for non-equity dilutive deals, royalty monetization, or out-licensing deals.

To your question, regarding the outlook for 2025. Well, one thing is to set expectation with you when crossing the 1 billion mark.

It's even better to beat these expectations. We need a little more time to see the uptake here in the U.S.

Get also, here pricing in Japan for Clazosentan. Get also see our pricing.

In the European countries, as you know, it's a whole race to launch a drug in Europe following EMA year approval. But we are confident that we'll be above CHF1 billion, i.e a beat this expectation.

Coming to the OpEx, we're first committed to profitability, so if the sales are not at the level we expect, we will adjust the OpEx. It's really a commitment of the whole team and we discussed it yesterday.

We see a U.S.. team they -- no we're -- we grant them all the financial means in order to meet their objective.

And it's only a one way. you succeed as Simon said.

So it will be a really -- it will be a really an exercise depending on the ability to grow our sales and to adjust accordingly but they're having better profitability as the OpEx.

Okay. Thank you.

Thank you, André. Operator, next question please.

Thank you. I'm afraid I'm going back to QUVIVIQ and the U.S., and a little bit on Europe.

Can you tell us how importantly elderly market is to the overall demand? And when your latest thoughts on when you might be able to get Medicare coverage.

If we look at the script as simple analysts, we tend to look back at the initial scripts of BELSOMRA, for example. Is there anything that we should look out for, that is going to different with your QUVIVIQ launch as against the higher levels of couponing, which will mean that there's a shorter period of time, where there's a more depressed initial ramp, despite good penetration?

And I wonder if you can tell us a little bit about the EU negotiations that you must presumably be starting and how we should think about Europe as an opportunity on top of the U.S.? Many thanks.

Yes. So the elderly is a very significant population for us on several accounts.

One is, the prevalence of insomnia in the elderly is high. Actually the plus 65s account for significant parts of the market.

And actually they are the ones most underserved because the zeds and the benzos really not not use well in that population in the US there. They are on the beers list, they recommended that those brokers are not used.

So you've got a population that is not sleeping well, is that risk and is almost more undeserved than the rest of the population, so we see a big opportunity. And actually if you look at our clinical data, the clinical data that we've generated a very impressive in the elderly.

You look at the Sunderland's rate in the over 65's, and you can see it in the Lancet supplement, our Sunderland's rate in the over 65's on the 50 milligram dose is 0.8%. So we've got a very differentiated profile within the elderly population, so we see a big opportunity in the over 65's.

In terms of access to Medicare, if you look at the straight line timing, we would be looking at January 24 for access. Because obviously that's just the straight process that we have to go through given the timing that we are launching.

That said we are going to be talking to CMS and to some of the plans to see whether we are able to accelerate based on the need this population has, and based on the profile of the product that we have in our hands. We don't know how that will work out, so we would hope that we can get a product added off-cycle in earlier than Jan 24.

But that's yet to be confirmed or determined, obviously. In terms of BELSOMRA and ramp.

First of all, BELSOMRA didn't have a bad start. So actually, if you look at the ramp of BELSOMRA for the first four to six months, it was actually quite good.

The problem is it then essentially went flat because the product didn't deliver on efficacy. So I think we will see, I think a ramp that should match or exceed BELSOMRA.

But I think it's -- the really important thing is what you see after six months. And does it continue to grow, and are we getting repeat business.

Because ultimately that's what's going to drive the long-term value, if we actually get patients on the product, they like it, they respond well, they want to stay on it. And then that's really as I say, what will drive the long term.

And Europe -- so I think Europe is a big opportunity actually. And I think people are probably underestimating it.

I think the regulators and even the payers are almost more concerned about the use of zeds and benzos than we see in the U.S. And you see in Germany for example, they restrict access to four weeks only in the U.K, it's 2 to 4 weeks.

So patients who basically have symptoms for more than 2 to 4 weeks have no options or total available to them. And we're going to come in with an indication, of course, that is chronic use based on our three months data and our 12-month extension.

And we're the only door that will enter the -- into the European market. So we're going to stand alone in a market where there's no other product that can be used for long-term use.

So we're seeing great, great interest, and great receptivity amongst the opinion leaders in particular. And in our early conversations with payers, and we're talking to Germany and the U.K.

at the moment. There is significant interest in the product because of their natural concerns about the use of sets and Benzos.

Thank you very much, Simon, very clear. On that note, I did get a question through the webcast that was very focused so I thought I would slip this one in, and it concerns the couponing and Andre, if you could provide some clarity as to how couponing is going to be accounted for, in terms of revenues, how does that function?

A very detailed question but I think it fits in nicely here.

Yeah, no -- SI couponing costings is -- in SI deduction between gross to net sales. So SI 120 million net sales that we guided for 2022 includes your couponing.

Okay, very clear. So the a 120 basically already takes that into account, because that is already deducted for.

Okay, Operator, next question, please.

Hello, James Gordon JPMorgan two questions, please. One was about revenues in the guidance for this year, so that a CHF120 million in sales, is that including a double-digit revenue contribution from PIPLAZ or is the vast majority of the 120 going to be QUVIVIQ and QUVIVIQ daridorexant I still say worriedly to not launching until May.

Are you expecting that much stocking or otherwise might have been very back-end weighted. So to manage our expectations, because two-thirds or three-quarters of the 120 end up being in Q4 this year or do you expect to more even spread?

And then just one other question was on the 25 top line target, I saw that you don't include -- we don't include clazo in the west or apro how much of that is because you still see significant risk around it versus the chances if being divested. You, How confident are you in the two things on a relative basis?

Thank you, James. I think Andre on both accounts, you've probably know best how those numbers came about.

Yeah. James, we don't want to disclose the breakdown between QUVIVIQ -- mainly U.S.

lower because it will be really launched in late Q4 in Germany and Italy, so we're almost no sales in Europe. So it's mainly U.S.

But it also include a significant amount for Clazosentan in Japan. Of course, the amount will also depend on their speed of uptake for clazo.

But also of course, we see a price, we are currently negotiating with the relevant bodies in Japan. If you look at your phasing as you understand their speed of uptake you won't see, especially with your co-pay and couponing, you will -- in order to gain its early adoption as Simon mentioned, you won't see much sales reported in Q2, but increasing over time, Q3 and of course Q4.

Of course, moving forward, we expect to see exponential curve in '23 and beyond. Back to 25, yeah, as I said, then you're right.

Not speculate on any additional approval. 1 billion, and again, as I said, we hope that we'll be able to meet these expectations will be mainly daridorexant, mainly U.S.

but Europe, depending also on the price that we'll be able to negotiate. It could be quite significant by 2025.

And here, again, we only include the EU for U.K., Canada and Switzerland, not adding any other countries in this staggered approach. And for clazosentan, I think that we will -- it's under -- it's like QUVIVIQ in Europe.

In my view, it's significantly underestimated by all the analysts and I hope we will be able to positively surprise with the sales of clazosentan in Japan.

Thank you, Andre. Can I just very quickly follow-up, the 145, does that include any kind of stocking?

The 145, you mean the 124 net sales plus the 25 --

Exactly.

From deferred revenue. Yeah.

It includes the normal stocking obviously. But it's a low proportion, especially for Japan.

And of course, slightly higher for daridorexant in the U.S.

Okay. And Jean-Paul, do you want to give another outlook on how bullish you believe Apro is going to come through as James put out the question whether that was one of the reasons why it's not included in the numbers.

I think you can never be a 100% sure, but this program has been based on the FDA recommendation it's really the FDA we designed with us. And they told us, we want this program for registered and potential, so I don't think there is if the study is positive regulatory risk.

And the results as I said, looks outstanding. So I think there is a very, very low chance of failure at this stage we are now with this program.

Okay. Thank you, Jean-Paul.

I'm aware that we already ten minutes after the hour. We're going to let us continue to run, Operator, are there more questions?

Hi. Just a few left for me, thanks.

If you could, what would be kind of reasonable price per patient for us to consider for [Indiscernible] in Japan. And then finally, just on your marketing strategy for daridorexant, how the roles is kind of split between yourselves and Syneos, and what proportion of patients are seen outside of the primary care setting?

Thank you.

Thank you, Lucy. Simon, do you care to take both of those?

Yes. I'll take those.

Yes. We're not in a position to disclose price on clazo in Japan at the moment.

We are in the negotiations with the authorities. We should -- you should see that in April when we conclude.

So hopefully your question will be answered in a few months from now, but we're not in a position to disclose that at this point. In regards to Syneos, essentially Idorsia is fully in control of the strategy and all of the core commercial capabilities in the U.S.

So we have -- obviously the marketing, the medical market access, price, and strategic control of the brand. Syneos is essentially a salesforce partner and they are providing our salesforce support.

We have done that in a creative way with the revenue auction for them, to whether they can gain some upside if they perform well. But essentially, the costs all run through the OpEx, it's a contract sales force that we've done it in a way that we allow them to have performance benefit if we overachieve, but essentially they are the sales force.

But we're in control and drive all of the strategy and the strategic elements of the product.

Thank you, Simon. So I've got another question coming in through the webcast, asking, this one's for Jean-Paul.

We've got so many milestones coming through. The share price doesn't seem to want to always react to them.

What is, what are your thoughts on how the share price decoupling is from all of our milestones.

I think -- thank you, Andrew, because this is a very often question asked. And I think that we at Idorsia, we the board and -- with the management, we have decided, and this was very clearly explained by André, we are guiding on basically the base case, which we have described, which is Dari in U.S., Europe and -- U.

S., Europe and Canada. And clazosentan in Japan.

That's it. All the rest is upside.

And this is unusual, this is unusual into the biotechnology field where most of the companies are valued and their stock price depend on sometime dreams and the all-bent expectations. And, you know, there is no limit to dreams and expectation and hope.

It's quite unlimited. It's very different when we make a base case like we do.

And that is the disadvantage of maybe people who are not really thinking in this way to value us. Just the value on this base case, is that don't give much value for the upside.

But that's, that's our strategy. And that means, for us that if we deliver on aprocitentan, and if we deliver on the clazo in U.S.

and Europe, if we deliver in many of the other projects, Lucerastat, maybe we are going to turn around the situation. If we succeed, we can really markedly change our stock valuation.

So I think it's much nicer and I have to say, not to be in a situation to disappoint the market, but to surprising on the positive side. That's our strategy

Excellent, thank you, Jean-Paul. Operator, do we still have questions in the queue?

Thank you for taking my questions. I have two questions.

Can you tell me something about your expectations regarding the peak sales of daridorexant? And my other question is that the equity ratio dropped from 41% to 7%, does that concern you?

Thank you.

I think on expectations Jean-Paul; I think versus if you give us an outlook of what you believe. And on the equity metrics, Andre, maybe you want to take -- tackle that.

I think that the drug, daridorexant has 14 years of patent life, at least. And so I think what is going to be the sales in 14 years, I cannot predict.

I think I can predict if we grow for the next 14 years because we don't have much competition. And frankly, that drug Ambien, or what is the -- I just forget the generic name, but it was selling for CHF4 billion in 15 years ago, when it was not -- before becoming generic.

And so I think that under these numbers I would be very disappointed in the future. And then that is -- the other question, sorry, I forgot.

The other ones for Andre on the equity ratio dropping from 41% to 7% as we -- basically we have a reflection of the convertible bond portion on our balance sheet. Does that concern you, Andre?

Not at all. To give a straight answer.

That's also taking the metrics from the U.S. GAAP accounts where, for instance, we know the convertible bond of J&J will ultimately convert into new shares.

But according to U.S.. GAAP, they say it's a conversion feature, leading to this accounting treatment.

Again, we're not funded to break even. We have various ways to fund the company.

And this should at one stage be reflected in the equity.

Excellent Andre. Thank you.

We did get two more questions, on housekeeping and pipeline on the web in written format. So on both Selatogrel and Lucerastat, Jean-Paul, where are we right now with those two compounds?

Selatogrel, Phase 3 fully in going, starting, we are really starting to include patients. We are opening centers by hundreds.

It's several hundreds of centers. And we are going to really get the pressure rising now this year, in terms of getting more and more patients recruited.

So that's going well. And we are quite in good situation for the auto-injectors to the production, everything is ongoing, so that's for Selatogrel.

And I think the other question for lucerastat, as I said, we got fantastic biochemistry that we got a very strong signal on renal function. And I would say also on the cardiac, we see some very interesting observations on the ecography, cardiac ecography.

Now, we are continuing to observe these patients in order to get a large number of patients treated for two years with Lucerastat. And we are starting the -- we will discuss with the regulatory authorities if we can use these data by comparing them with an artificial or easy to recall, if you want, control group, like it was done with Fabrazyme from Genzyme.

This was the way they got full approval. So we are going to discuss with the FDA.

But some of the countries have very different requests in terms of what is needed to approve such a drug in an orphan disease, and we are discussing with other regulatory authorities also. So I think at the end, I'm very hopeful that this drug can be approved in as many countries as we can.

Thank you, Jean-Paul. And then one more for André regarding flexibility of the commercial costs in 2022.

How much wiggle room is in that cost block that we are guiding for 2022, if the commercial ramp up were to be slower?

Well, for 2022 are not much, because we need to really properly launch a drug here in the U.S. You launched only once, so you need to succeed.

So it's really more stop and go depending on the uptake moving forward, '23, '24 and beyond.

Excellent, Andre. We've exhausted all the questions.

We've come to the end of this call. We've passed over the hour significantly, so thank you very much all for your ongoing interest in Idorsia and wanting to know how this story is going to evolve over the next few years.

It is very exciting, so stay tuned. Operators, please close down the lines.