Idorsia Pharmaceuticals Ltd

Good morning, good afternoon, everyone, and welcome to our financial update, now newly being hosted on a quarterly basis. We posted our third quarter nine-month results this morning at 7 a.m. Central European summertime. On the call with me today to provide additional color with prepared remarks and thereafter in the Q&A session are our CEO, Jean-Paul Clauzel, our CFO, André Muller, and our Chief Commercial Officer, Simon Joes. Next slide, please. As you know, we will be making forward-looking statements in this call. Hence, with this disclaimer slide, you have been adequately warned about the benefits and risks of investing in Eidosia stock. Next slide. With that said, let's kick it off. Jean-Paul, the floor is yours.

Okay, so thank you Andrew, and today it's my pleasure to introduce you to the great progress that Agdosia is making to transform itself into a commercial company.

Next slide. So many things have happened during the previous nine months of this year.

Now, first, and Simon will give you more precision about it, Daridorexan is becoming a global brand. In the U.S., it is soon going to become the first, the number one branded product in the insomnia field. PIVLAS in Japan is really progressing extremely well, since about 20% of the patients already with subacnoidal hemorrhage are treated with Kletozentan. André, we present to you the financial figures. As you have seen, we have made a sale in this back agreement to raise cash. And we are working on other non-dilutive measures to bridge the funding gap to the profitability level. And finally, the pipeline is progressing very well. Phase three data of aquacitantin will be shown at the American Heart Association Congress. and the phase 2B of the SceneryBot will be presented at the American Congress of Rheumatology. But as you know, so we are preparing for the readout of the REACT study for clasosanthin in US and Europe, and many other projects are moving on. Next slide. So, Simon, the floor is yours and you can explain the progress of QBB and the other drugs, of course.

Thank you, Jean-Paul, and good morning and good afternoon, everybody. As Jean-Paul said, it's a transformational time for Eidosia as we continue to gain momentum with our first two product launches and build our commercial organization. And I'm pleased to be able to share with you today the progress we're making with both Qvivik in the U.S. and PIVLAS in Japan. And I'll give you an update on our first launches of Qvivik in Europe. Next slide, please. So I'll start with Qvivik, which is, as you know, we launched in the U.S. in May. Next slide, please. And I'd like to begin by reminding everyone that our net sales do not reflect demand or prescriptions dispensed at this stage. As I highlighted in the half-year earnings call, to enable early patient access to Qubivit, we're offering a comprehensive copay program, including a free first 30-day prescription. We know this strategy is helping with early product uptake, and I'll show this to you shortly. And this demonstration of demand is critical to support our ongoing negotiations with payers. Now, in anticipation of questions later on, I will tell you that we are in continued discussions with all the main commercial plans. And although we're making progress, we have not yet aligned on a rebate level that we believe reflects the superior value of QVIVC. But as demand grows through the fourth quarter, we expect to be in a much better position to finalize contracts as we move into 2023. Next slide, please. Turning then to demand and prescriptions dispensed, you can see here the growth in prescriptions since our launch in May and the positive change in trajectory in August and September following the launch of the branded DTC campaign. In September, we exceeded 10,000 prescriptions dispensed with more than 70% being written for the 50 milligram strength, which is the strength we believe will provide the best efficacy and likelihood of successful trial, which we know is really important in this category. The graph on the right shows a breakdown of total QVivic prescriptions and the prescriptions coming through VitaCare and those being reported by IQVIA. As you know, and as we talked about last time, VitaCare is a specialty pharmacy services company that manages a key component of our patient support program, but IQVIA does not currently include VitaCare in its sample bank, and therefore, its syndicated data underreports prescriptions for Qvivic, hence why we're providing these data to you on a quarterly basis when we have these calls. Within these total prescriptions, we are seeing increased growth in refills, and refills now represent approximately one-third of prescriptions. Next slide, please. Our writer base shows a similar trajectory to our prescriptions, with continued month-over-month growth. Again, we see an increase in growth of prescribers following the launch of the DTC campaign. In the chart on the right, you can see the split by specialty, with 63% of our writer base being in primary care and 22% in psychiatry. This reflects the efforts of our sales teams that are focused on these two key audiences. and the split is consistent with how the overall insomnia market is structured. Next slide, please. Now, this is an important chart, and I showed it to you last time. It shows the traction we have gained in just five months from launch in new patient acquisitions. As I highlighted in the earnings call last time, we passed Davego after only six weeks from launch. A few months on, and we're closing in on Belsomra and expect to surpass it soon to become the leading branded insomnia medication in the U.S. in new-to-brand prescriptions. This is an important milestone at this stage in our launch, not because the Dora market is important as a source of business, it's obviously too small, but rather because it's a clear demonstration of physician receptivity to the profile of Qvivix. To have got this far in five months when the other two products have been on the market seven years and two years, respectively, I think speaks volumes to the perception of the product by physicians. But this, of course, is only the beginning, and the potential for Qvivic is, of course, much greater. But this will require us to grow the DORA market as well as being the leading product within it. Next slide, please. We are doing just that. Qvivic is driving growth in the DORA market. This chart shows MBRXs for the total DORA market in 2021 and 2022 year-to-date. As you can see, the market was actually in decline until the launch of QVIVC in May 2022, after which we have seen marked growth of the total market driven by QVIVC. So we're not simply just taking share from within the DORA market. Next slide, please. Our goal is to become the leading product to treat insomnia in the U.S. Becoming the leading DORA is simply the first step on this journey. But clearly, in order to do this and to expand the DORA class, we need to source our business from either new patients or patients on other classes of medication that dominate the U.S. market. As you can see here, the IQVIA data shows 42% of patients receiving Qvivix since launch are new patients. and 58% are switched from another therapy. And then the pie chart on the right shows you where we're getting these switches from. 33% are coming from Zed drugs, 27% are coming from benzos, and 26% from antidepressants, including, of course, Tretadone. And so we're very encouraged by this profile of our source of business. Next slide, please. The acceleration we're seeing in both prescriptions and prescribers of Qvivic is tied to our DTC campaign. We launched this in mid-August with world skiing champion Lindsey Vonn and our second commercial featuring actor Taye Diggs just a few weeks ago. As patient ambassadors, Lindsey and Taye are both currently taking Qvivic and having positive experiences with the product. These TV commercials, as well as surround sound messaging, by organic paid and social media resulted in an immediate increase in patient requests for Qubivic and in new prescriptions, MBRXs. Just to give you a few highlights, we've seen a 79% increase in traffic to our branded website. By the way, we have about a million people who have visited that website now. 173% increase in the unique co-pay registrations for people on the website, who are actually looking to download a copay card and an estimated 38% increase in new patient acquisitions, which essentially is taking our MBRX trend and then looking what the delta is post the DTC launch. Obviously, we expect that the impact of our DTC campaign will continue to build over time. And as I mentioned before, this increase in demand also provides a good basis to support our ongoing negotiations with payers. to secure access to Qvivic for patients at a rebate level that reflects the value of the product. Next slide, please. Now, looking beyond the U.S., Qvivic is on track to become a leading global brand. Following EU approval in April, we are ready for our first European launches in Germany and Italy next month, and I'll speak about that more in a moment. We have also completed our phase three study in Japan, and released the positive top-line results a few weeks ago. We're now preparing the marketing authorization application and are looking forward to bringing Qvivic to patients in Japan with our local partner, Meshida. And in contrast to the U.S., the DORA market in Japan with Suvarexant and Lembarexant represents approximately 20% of the insomnia market volume already and continues to grow. Next slide, please. Turning to Europe now, we see a significant opportunity for Qvivic as the first and only DORA available to millions of patients suffering from chronic insomnia. In this chart, you'll see the insomnia market volume in the top five European markets, where we've included an estimate of the off-label use of antidepressants and antihistamines to treat insomnia. It may be surprising to some to see that the volume market in the top five European markets is actually larger than the U.S., both in terms of standard units and on a per capita basis. It's also striking to see how different the product usage pattern is by market and the high usage of benzos in Italy, France, and Spain, this despite the concerns about the safety of the long-term use of these sedating products. You will also notice the relatively low volume in Germany and the U.K. This is due to these countries having greater controls in place to restrict the use of the sedating GABA agents, not because there's a lower incidence of insomnia. We believe Qvivik can help address the significant unmet need for safe and effective treatment options for chronic insomnia patients in all of these markets. Next slide, please. And physicians and patients in Europe are genuinely excited about the prospect of Qvivik. In market research we have conducted last year across the big five European markets, 91% of healthcare professionals indicated they were likely to prescribe Qvivic, and 85% of patients said that they were likely to ask their doctor about Qvivic, with 37% being extremely likely. These results are well above benchmarks for market research of this type on new products prior to launch. And we are actually hearing similar positive responses to the profile of Qvivic from key opinion leaders and doctors as we start to engage with them in our prelaunch activities. Next slide, please. The launch preparations in our early launch markets are well on track, and the local teams are actively engaging with medical experts and other key stakeholders to introduce Idorsia and Qvivic. In Germany, we will launch next month, November, with one year of free pricing. In the German market, there is a four-week prescription limitation for hypnotic and sedating agents known as Anlaga Dry. This is what I was referring to earlier about the sort of things people are putting in place to restrict the use of existing agents. So all these drugs have a four-week restriction on reimbursement due to the safety concerns. Now, earlier this month, the GBA issued a draft resolution that, if approved, would exempt Qvivic from this limitation and allow prescribing beyond four weeks in line with the EMA label. If this resolution is approved, Qvivic would be the only sleep medicine that would be reimbursed for adults in Germany for longer than four weeks. In Italy, we are also launching next month. Insomnia products in Italy are not reimbursed, so we will launch into the private market. At the time of launch, prescribing of Qvivik will be limited to specialists, which is actually something that is not uncommon for first-in-class CNS medicines. Next slide, please. So turning to PIV-LAS in Japan before I finish and hand to Andre. We launched PIV-LAS or plazacentin, as you know, in April to prevent vasospasm following an aneurysmal subarachnoid hemorrhage, a life-threatening condition which has a two- to three-fold incidence in Japan, more major than the Western markets. Next slide, please. I'm delighted with the positive trajectory we are seeing for PIVLAS since launch. We have generated net sales of 25.1 million Swiss francs since the launch in April. In terms of demand generation, over 80% of our target hospital accounts have ordered clazosanthan. and medical experts and neurosurgeons are supporting the inclusion of PIV-LAS in treatment protocols. We continue to see increased adoption, as Jean-Paul said, with approximately 20% of ASAH patients receiving PIV-LAS in September. This, of course, based on the estimate of the incidence of ASAH in Japan. We have also filed Clasicentan in South Korea based on the positive data from the Japanese clinical program and established a local affiliate there to prepare for the launch. So in summary, we are making strong progress in transforming Idorsia into a commercial company. I'm determined patients will get to benefit from our innovation by making Qvivic a leading insomnia medication on a global basis. The growth in demand of Qvivic in the U.S. means that we are close to becoming the leading branded insomnia medication in new to brand prescriptions after only five months on the market. We are also just weeks away from the launch of Qvivik in Germany and Italy, which will mark the availability of the first and only DORA in Europe. And of course, in the meantime, PIVLAS is performing strongly in Japan. I'm confident this positive momentum we are building will continue to grow. And with that, I will hand over to Andre.

Thank you, Simon. So next slide, please. Yeah, good afternoon, good morning to everyone. Thanks for your continued interest in Eidosia. Let's move to slide 21, please. Starting with the net results, I would say especially at least on the operating expense, Q3 is relatively uneventful. As you can see here, we have net revenue of 43 million. This consists mainly in the contract revenue of $16 million, of which $2 million is cash, and $14 million are deferred, and $27 million of net sales, as Simon indicated, $25 million coming from Japan.

Dear participants, please accept our apologies for the delay, so we'll resume shortly. Thank you.

Okay. Andre, can you recommend your comments? We seem to have lost the line.

Yeah, I don't know exactly when we were disconnected, but there was a trust explaining the US GAAP net results to minus 610. in U.S. GAAP EBIT and 25 million, of which 20 million for financial and 5 million for tax below EBIT. And of the 20 million in financial, mainly relating to the convertible bond financial expense, 13 million. Let's move to the next slide, please. So, going a little more in detail, we see a non-GAAP operating expenses. As you can see, we are almost flat in R&D. And contrary to our research, where most of the 86 million spent for the first nine months is really a fixed cost base, we have some CARC tox studies for approximately six to seven million. For developments out of the number of 133 million, the lion's share is relating to study costs and supply of drug substance or drug product, around 94 million versus 79 million for the fixed cost base in developments. Slightly further down, you will realize that the late-stage assets represent the majority of the study costs. We sell at around 25 million, including the development of the auto-injector. Scenario mode, 18 million. We see a Phase IIb care and the preparation for the initiation of the Phase III. Daridoxan is still high with 17 million, but Japan, which accounted for 8 million, and as you've seen, we have published top-line results in Japan that are really positive. And we have an unusual amount of, for leucerastats, with drug substance of 10 million in order to support the open label extension. Clazo, we still have 10 million, mainly relating to the reactor trials that should read out early 2023. And you see that only with these five late-stage assets, we have covered more than 90% or, yeah, close to 90% of these study costs. Marketing and selling, and GNA, of course, are the big driver for the increase with 358. So marketing and selling is slightly below 290, and GNA is slightly below 70 million. Ethics rates does not help, especially with the OPEX in the U.S. As Simon said, with the selling and the with Cineos, the contract sales organization, DTC, and the operating, commercial operating costs with the U.S. affiliates. The rest is split between Japan, UCAN, for the load preparation, as mentioned by Simon, and at central level. So with this, you see that the first nine months, we have 621 million non-GAAP operating expenses in, of course, a much higher due to launches across the globe, U.S., Japan, also preparing for the launch in Europe. Next slide, please. Cash flow, if we reconcile with the liquidity, so we started here slightly below 1.2 billion and we ended with slightly below 700. The non-GAAP OPEX, we just went through it, plus CAPEX and working capital requirements of respectively 23 and 33 million. As you see here, and we announced it a few weeks ago, the sale and leaseback transaction of 164 million gross, so net of transfer cost 162, plus other items of 21 that bridge us to the 695 million liquidity. Next slide, please. Here you just have the breakdown of the liquidity, and as you can see, our policy is really because we are Swiss operating company, also Swiss franc is our reporting currency, so we have out of the 695, almost 600 in Swiss franc, and 77 in U.S. dollar. The remaining are in various currency, Japanese yen and euro. Next slide. Finishing with the guidance, as you see, we confirmed the guidance that we gave from the beginning of the year with a non-GAAP operating loss around 785 million. and which would lead, including DNA, NSVC, to 840 million on the U.S. gap net operating loss. Next slide. Again, as we said, we see a same scope, i.e., what we know now, in the U.S., in Europe, U.K., Canada and Switzerland, Klaas & Tann in Japan, so not speculating on the upcoming results, notably for REACT. We believe that we will reach more than 1 billion sales in 2025. We'd like it to be 2024, but for the time being, it's 2025. and that with this level of sales we would become sustainable we will reach a sustainable profitability with this i hand over for uh conclusive remarks of uh with two uh two sample next slide next slide okay so thank you very much simon and i think that

I hope you have understood the progress we are making. And the year is not finished. Many things will happen this year. And we are working very hard. And I think we are going to see the continued increase of the demand for Qubit in the US. We are going to launch Qubit in Germany and Italy. As we said, many patients are really waiting for Juvédic in Europe. We will initiate the phase three program with Senderimod, and we want, after the presentation of the results at the American Heart Association, but we want to finish to end the five, the NDA for prostatitis this year with the FDA. And finally, we are actively preparing for the readout of the REACT phase three final study which will happen, the readout will happen first quarter 2023. Thank you very much. So, I hand over to Andrew for handing the questions.

Thank you very much, Jean-Paul. So we have come to the end of our prepared remarks and also to the past the bottom half of the hour and are ready to take your questions. For those listening over the internet or webcast, you may also ask your questions via the chat box on the website. Operator, we are ready for the questions.

Thank you, dear participants. As a reminder, to ask a question over the phone, you will need to press star 11 on your telephone keypad and wait for a name to be announced. Please stand by. We will compile the Q&A to you. This will take a few moments. Thank you. Now we're going to take our first question. The first question comes from the line of Harry Sefton from Credit Suisse. Your line is open. Please ask your question.

Brilliant. Thank you very much for taking my questions. I have a few to start with on QVivit. I recognize that it's still early in the launch, but what have you seen in terms of retention rates to treatments? given that lower retention seems to be the issue for Belsomera after its strong initial launch. Then you mentioned that you've not managed to agree an effective rebate for QVivic, but can you help us as to how the payers think of this? Is there an ISA type review that would give us an independent view of the value of such a brand over the very cheap generics? And can you maybe also help us in terms of the level of rebates that we might expect versus what we can see for Belsomra, which seems to be at about 60% rebate? Then on the European launch, we understand that Dora's did launch in Europe partly based on pricing. What are your views on a reasonable price in Europe and what increasing costs should we expect for the European launch? Thank you.

Thank you, Harry.

Simon, I think it was all for you. Sure. I wasn't expecting a question on QBID. So, hi, Harry. Taking them in order, on retention rates where, I mean, as I said in the opening remarks, we're seeing about one-third of our script volume now in refills. The longitudinal data is harder for us to pin down right now because with the VitaCare IQVIA mix, If a patient starts in VitaCare, but then they flip to the retail channel, then what is actually a refill patient gets cancelled as a new patient. So we're trying to clean all that up with IQVIA, but we think we've got a sort of compliance rate, if you will, in the sort of 40, 50% range, which is common and sort of in line with chronic medications in primary care. But I can't give you a lot more than that. But we're pleased that we're seeing growth in refills. And as I say, we're about a third of our volume is now in refills. And the refills are growing month over month, which is important, clearly, as you say. On the rebate, I'm not obviously going to give you levels and percents, but maybe to your point about the thinking of payers. This is sort of how it goes. They've got two existing doors and they've got rebates on those. They we've had many meetings with them. We've talked about the clinical profile and they see the benefit of the clinical profile. They want to see that play out in clinical practice and in demand. And if we're to want to have a sort of net premium price, if you will, which we believe we should have for the brand. So really, we need to put daylight between us and the other two DORAs in order for us to truly be able to demonstrate to them that this clinical profile that we presented to them that comes from our phase three program is truly going to play out in practice. Because if it doesn't, they're going to end up with a third DORA, and then they just divide their existing DORA uh market into three and and pay more less rebate if you will which sort of doesn't make sense i think once the demand grows and we put as i say clear daylight between us and the other two then i think we'll be able to demonstrate clearly to them that the product is different physicians and patients see it as being different and then that that sort of changes the dynamic so it's a it's a little bit of uh cat and mouse at the moment as we go into those conversations. I think, as I said last time, we could have a deal now. I mean, it's not that we're not talking numbers with these plans. It's just that we don't want to pay what they want now because we haven't pulled away from the other two products. In Europe, the other two Zoras, as you rightly say, didn't launch. We can't I don't fully speculate on why that was. I think perhaps pricing was something or just their sort of fear of entering a generic market in Europe. I also think there may be something in the clinical profile of the product. The European regulators are more biased towards subjective endpoints. And if you look at Belsomra particularly, the subjective data on Belsomra isn't great. So whether it was a combination of the regulatory pathway and the payer pathway is our suspicion. Either way, I think, you know, we feel very good about the opportunity in Europe, and we feel good about where we are with the discussions with payers. And I think the evidence we've just seen from Germany, where the GBA, now recommending that Qvivic is exempted from the four-week prescription limit also demonstrates that payers are looking at this as a different product from the Zevs and the Benzos, which are limited to short-term use. And that separation helps a lot with our pricing discussion.

Thank you, Simon. Thank you, Harry, for the questions. Operator, next question, please.

Thank you. Now we're going to take our next question. And the question is from Manos Mastorakis from Deutsche Bank. Your line is open. Please ask your question.

Yes, thank you for taking my question. So first of all, I just wanted to ask what is the timing for a first renegotiation of commercial contracts with major PBMs? And secondly, what are the approximate peak sales opportunities according to the REACT What do you think it could represent?

Okay, Simon, I think you'll take the first one. And then on the REACT data, Jean-Paul, do you want to tackle Clazzos and TAN as to what that represents?

I can answer Clazzos. I won't give details.

And on the first question, on the timing of the first contract, I can't tell you, to be honest. This is going to depend on, as I said before, it will depend on the shape of the demand curve as we move through the fourth quarter. And we're trying to triangulate time with the demand and the rebate level that we believe is fair. And you need to put all three of those things into the equation. And then you say, right, yeah, we've hit the sweet spot. I can't predict when that's going to be exactly. I would hope that we'll start to see us in a position with the demand curve as we exit the end of the year that we'll be in a position to have much more robust conversations as we move into 2023. But I can't give you an exact time.

Jean-Paul, on where you think patients benefit most on REACT and how many could that be?

I think that, you know, the Japanese market is a big market. But I would say that we see Europe and the US and also at least in terms of number of patients as big as the Japanese market. So you see the numbers already in Japan for the first few months of launch. I think that there is no competition. So I think it's going to be a very large market. But I would not give numbers now. It's certainly many hundred millions. Can it be a blockbuster? I think it's a question mark I would not commit. It will also depend a lot on the React results because we have, frankly, we have optimized We have now, in the REACT study, the patient selection has been optimized in order to really have the highest benefits. And the benefits will also condition the price of these drugs because by giving clazodentam, we prevent a lot of interventions, a lot of day of hospitalizations. So the extent of the effect will also condition the price. and certainly the sales potential.

Thank you, Jean-Paul. Thank you, Manos. Operator, next question, please.

Thank you.

Now we're going to take our next question. Please stand by.

And the next question comes from the line of James Gordon from JP Morgan. Your line is open. Please ask a question.

Hello, thanks for taking the questions, James Gordon, JP Morgan. A few questions, please. First question, QBQ in the US. So I heard about a best position to finalize reimbursement contracts in Q4. But under what timelines do you now think you might have broad commercial player coverage? and what the steps are going to be that are going to get payers to change their mind. Because did I hear right that you needed more data? Is there specific data that you're collecting that you think you're going to need to give payers and say what timelines could you have broad coverage? Second question was the reiteration of the 2025 profitability target. So clearly QBQ reimbursement is going a bit more slowly than initially hoped for. So is there an offset? Is it pivoting better or are you going to spend less? Or is it you still think you're going to be in the same place for QBQ in 2025 It's just it's going to have a different shape. And then third question, we haven't heard yet on divestment of any of the royalties there. Is there a gating factor to get that done by the year end? Or is that not plan A? Is plan A that you do something else that's a non-equity dilutive funding action?

Thank you, James. All right, Simon, do you want to have another kick at the QVIVC reimbursement? And then we can give it to Andre for some funding.

Yeah, I don't think I've got an awful lot to add to what I've already said. I think, James, in terms of the data that we need, fundamentally it's prescription demand. So we are very focused now on driving prescription demand, particularly where we can through the 20% of the market where we have open access. And as that demand grows, that's what's going to sort of, if you like, tip the balance in our conversations with payers. There's no, that's the sort of data that we need. And the timelines, as I said, I think that we'll likely be looking to hopefully contract as we go through into 2023. But it'll take us some months before we get to a significant proportion of that coverage as you'd expect.

Andre, do you want to take the profitability in 2025 and the APRO funding and whether there's a gating factor there?

Yeah, regarding the first one, the outlook for 2025, yes, we have a delay in the uptake of Curovivac in the U.S., no doubt. Many reasons for it. Simon alluded to it. But we fundamentally believe that it's only a delay. it does not impair the potential of Qvevic in the US. And in Europe, from the initial interactions that we have with the main countries, we believe, not only because we are the only DORA, that we have also a nice business case in Europe. Plus Japan with PIVLAS, The uptake since the launch late April here is really in line with what we expected. We are only handicapped by the FX rate, which unfortunately affects the sales number in the nine-month financial statement. So this, even if we have some delay, we believe that the 1 billion mark can be achieved in 2025. And this would bring us to profitability. Regarding the OPEX, you've seen already a trend in R&D. It's fixed. I gave you also some indication on where we spend in clinical development on the study costs who are moving forward. It's mainly Selatogrel and Senerimod that will drive the study costs for the next few years. And we also hope that we'll have other clinical compounds that will be advanced to the next stage. nothing meaningful here. So it's really a question of, at the end of the day, it's really how commercial will deliver and contribute to cover what I could consider between R&D and H2 GNA, the H2 cost base, if you want. But still planning to or aiming for profitability in 2025. Your second question regarding funding and the potential royalty monetization deal. Yes, first, all investors have access under CDA to see data generated with the precision trial, all correspondence with the FDA. You know, due diligence is valid for even outlicensing a deal. If you ask me, I believe it takes too much time, but that's what investors are doing, especially in the current environment. So I'm pretty confident that based on the discussion we have with a few potential partners, that we can ink a deal before year-end. And it's a form of royalty monetization. Is it strictly a royalty monetization or sort of a bond with a royalty reimbursement or royalty sweep? in it or a structured debt with collateral or security on some assets, including a portion of the royalty entitlement from Janssen on Aprocit Antan. This remains to be seen. For the time being, we have not yet to be a very clear binding term sheet, because then we would... We would definitely go from an exclusive discussion, but still hope to be able to close such a transaction before year-end.

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

Thank you.

Now we're going to take our next question. Please stand by.

And the next question comes from the line of Peter Verdelt from CT. Your line is open. Please ask your question.

We can't hear you, Pete. Okay, operator, then we'll take the next question. Maybe it comes back in.

Perfect. Thank you. Now we're going to take the next question. And it comes from the line of Rosie Turner from Jefferies. Your line is open. Please ask your question.

Hi. Thank you very much for taking my questions. So I'll just do three, if I may. Just going back to the comments made around this kind of non-dilutive royalty sale, I think at the beginning in the opening remarks it was said that this was going to take you through to profitability, i.e. that would mean kind of funding gap closed until 2025, whereas I think on the previous call it was meant to cover 12 months. So can you just clarify kind of what period we're going to cover in terms of funding gaps? And then on PIVLAS in Japan, you said you've reached 80% of kind of hospitals. Does that mean there was an element of stocking in the numbers this quarter? And then finally, just thinking about Germany, so it's free pricing. Do you expect that to last for the full 12 months, or is there a potential for getting that kind of added therapeutic benefit payment added any sooner? Thank you very much.

You want to take the timing option of funding?

Yeah, I'm not sure it's not a misunderstanding because, and I don't know which slide you're alluding to, but the transaction that we hope to close before year-end would not bring us to profitability. So, we will need in due course down the road to raise additional cash.

Yeah.

And should I pick up the other two? Yes, sorry. Hi, Rosie. No, I wouldn't say there's any material change in stocking in the third quarter. Obviously, that was really in 2Q as we talked about then, but I would say there's no, material change. There's no material stocking change in Q3. And on Germany, no, I don't think so. And I think the way the system works, essentially, we have the 12 months for free price. During that 12 months, we will negotiate the price that will become, if you like, the price at the end of 12 months. And that will be based on, obviously, the added benefit that we get when we go through that assessment. So I think we expect to have it for 12 months and then We'll have a negotiated price at the end of that, based on our negotiation in that year. Thank you, Simon. Thank you, Rosie.

Operator, do we have Peter Vadold back in the line?

Yes, we do.

I will just open his line. The next question comes from the line of Peter Vadold from Citi. Your line is open.

Thanks. It's Peter Vadold here from Citi. Hopefully you can hear me this time. Andrew, can you hear me?

Yeah, we can.

Yeah, sorry about earlier. I've got a few questions. Thank you. I've got a few questions, one for Jean-Paul, one for Andre, one for Simon. Jean-Paul, you'll probably say be patient and wait a couple of weeks before we see the precision data for AHA, but can we at least just kick the tires and I'd like to get your view on SYNCORS back to just that data. in treatment-resistant hypertension, 20 millimetres systemic blood pressure reduction, 11 millimetres placebo-corrected. Is this a benchmark that you think a prostatant can meet or exceed when we see the data? I realise you can't talk to the actual numbers, but I would like to get some benchmarks from you. Secondly, Andre, just a couple of high-level questions on OPEX for this year and next. The budget at the start of the year implied over $900 million of spend. We know revenue are coming in lower than expected, FX headwinds are stronger, but guidance has been unchanged and it's obvious that you're very comfortable meeting expectations. I just wanted to get a handle on whether this is due to just simply R&D phasing or or marketing spend coming in much lower than expected. And then, again, I realize this is not the forum for guidance for next year, but just conceptually, OPEX for next year, should that be flat in absolute terms, or do you fully expect it to grow further, given the pipeline and commercialization efforts around the globe? And then lastly, Simon, I'm sorry to come back to QB, the chicken and egg situation on revenue and access, but just a couple of tarifications in terms of pushing you on those prepared comments with regards to commercial access in 2023. Is that something that is probably going to be later in the year, or is there any sort of nuggets you can give us about commercial access opening up sooner? And can you confirm that Part D access is unlikely to come through until 2024? So, sorry about a lot of questions there, but hopefully there's some interesting answers.

Thank you. So, maybe I take the first one about... Yes, go ahead, Jean-Paul. Yeah, I think, you know, people always make a big mistake when they evaluate cardiovascular drugs, because you have to look at a few things, and this will be interesting to see what we have done in precision. First of all, you know, which patient do we treat? We have really, in precision, taken real resistant hypertension, which means taken with three drugs, and I would say more than 50% have four anti-hypertensive treatments. In many of the previous studies, sometimes there are only two drugs, so it's not really resistant hypertension. It's basically an add-on therapy, simple add-on therapy, without the definition of resistant hypertension. The number two is how many percentage of these patients have renal failure, have diabetes, have heart failure, Did we exclude these types of patients in the protocol? And finally, there is the efficacy. Is the efficacy limited to a subgroup of patients? Is it in every patient? And finally, of course, the safety, especially renal failure. And you know that, for example, with spironolactone, with aldosterone, uh inhibitors the risk of renal failure on top of existing therapy is very high so this is the whole picture that you have to look at when you really evaluate the cardiovascular drug and and then let's go to ahs to see the results okay audrey now yeah um

Peter, to your question for 2022 guidance, yes, you're right. With the initial plan, which was gross profit generated from net sales and contract revenue north of 100 million and OPEX around 900 million. Sales will be below what we initially planned. notably in the U.S., and also because the FX rate in Japan will definitely not help. Contract revenue should be higher because I'm also confident that we will announce the outlicensing of QVVIC for China before year-end. We've done good progress. We see a selected partner. But the revenue will be slightly lower than initially planned. And in order to stick to here again, We had a few tasks ascribed to various departments in R&D, in commercial, in G&A, just to make sure, and which will be reflected in the lower OPEX in order to meet the guidance. So that's for 2022. For 2023, I'm sure you anticipate already my answer. You need to be patient and wait for the full year results early February 2023. But what you need also to understand here is that with respect to the net sales, we need a few, there are a few assumptions, and we need more data points. And notably, we see volumes in the U.S. Of course, when we could get payers' coverage in the commercial space, mainly we see three main PBMs. And this will drive, again, for net sales. With respect to the OPEX, yes, that's why I also wanted to give you some cover on CR&D. Some of the huge spend in study costs will progressively go down, including Japan. Lucerastat with the open label extension, and this year was really relating to the supply in drug substance and drug product to support the open label. Clasazentan once REACT is finished. So, moving forward, you will mainly see a study cost will be mainly relating to cell autogrel, still a long way to go, where we see enrollment of patients, which is gathering speed, and the initiation of scenario mode. I would say R&D, yes, slightly going up. We see a fixed cost base, but on the study cost, we should be able to stabilize it, if not going slightly down. So it will be really in the commercial organization where We definitely need to put some marketing and selling in order to launch in Europe where we will definitely have an increase. But that's again the big picture. We need to refine it based on more data points, mainly in the U.S., before coming with the guidance for 2023. Hi, Pete.

Let me take the second part first, because it's a bit more straightforward. I mean, we're essentially now in the process of bidding for the 2024 Part D formulary. We would try to get something earlier in 23, but I wouldn't bank on it. I think that our base case assumption is that Part D will come in in 2024. In terms of commercial plans, I would be, I don't know, as I said already to other questions, we don't know the exact timing and it'll also depend on obviously that demand and rebate and timing matrix. I would be disappointed if it is later in the year as you sort of posed your question. Conversely, I wouldn't have any expectation that all of it's going to arrive on January the 1st. I just think we need to see how it plays out. But I would be disappointed if we start seeing this arrive later in the year.

Thank you, Simon. Thanks all for you. Thank you. Thank you, Pete.

Thank you. Operator, next question please.

Now we're going to take our next question. Please stand by.

And the next question comes from Thibault Bauderin from Morgan Stanley. Your line is open. Please ask your question.

Hello. Thank you for taking my questions. Just the first one, thank you for the color and the clarification on OPEX. I just want to spend a little bit more time on the composition of marketing and spending going forward. If we look at the spending this year, Part of it was DTC campaign. Part of it was a big push on the Salesforce for QVVic. So just when we try to think about how you're going to support QVVic going forward in the U.S., we expect more of this DTC. It's going to be more of a traditional commercial effort from there. So just if you could comment a little bit on your commercial strategy going forward. Second question, on the start of the Phase 3 programs for SceneryMod, what is the kind of condition to start a study in order to have the the full data from the phase two. Is it possible that you could wait a little bit longer to make sure that UVic is really taking off before engaging with the expense of the program start? And then last question on GCR-STAT. You mentioned that you're discussing with authorities in the first half of next year. Is the filing possible with the current data that you have in-house right now? Thank you.

Okay. Simon, do you want to take the first one on the structure of how you think your team is going to be spending next year?

Yep. Go ahead. Yeah, I mean, you're absolutely right. I mean, the sales force and the DTC spend represents the bulk of the OPEX in the U.S. Those are, if you like, the two big pillars of spend. Both of those were. in the 2022 numbers to a large extent, because of course the Salesforce came in probably sort of February time. And although our branded advertising started in August, we were doing some unbranded activity in the first half of the year. I don't see that changing particularly. I mean, I think we know that we need a Salesforce. We need to continue to educate doctors and make sure that they're, familiar with the product and the benefits. And we also know, and I think the reaction to the DTC campaign is bearing this out, is that, as we've always maintained, this is fundamentally a product that is going to respond well to consumer activation because of the nature of the disorder. And we're going to need to continue to invest in educating consumers and encouraging them to talk to their doctors about Qvivix. So I think moving forward, we continue to expect to the Salesforce and DTC as the two large pillars of our strategy and of our OPEX.

Okay. Thibault, I didn't quite understand your second question there in between.

Yes, sorry. So it was about SceneryMod and basically I think before you mentioned that you would start the Phase 3 program for SceneryMod before the end of the year. I don't know if this comment still stands or is there anything that could delay the start of the Phase 3?

Okay. I think I'll refer to Jean-Paul for both those questions, SceneryMod and Lucerestat.

I think that – do you hear me? Sorry, I just – Yep. Yeah. Do you hear me well? Okay. No, just for SceneryMod, it doesn't make sense to wait for SceneryMod because we have spent this year already quite a large amount to prepare the phase three, to recruit the centers. So now we have to start – And I think that, of course, this is a competitive field, and we believe we can be one of the first or maybe the best oral product in lupus. And if we wait, we will have lost this opportunity. So we have now discussed with the FDA. We have an agreement on the clinical plan. Now we have to move, and that's what we are going to do. I think in terms of Lucerastat, we are really now looking at the results because many patients have two years of treatment under Lucerastat. We can evaluate the continued benefit. And I think that what we are starting is to discuss with different regulatory authorities their approach to this data, and this is really what will happen in 2023. This year, I have to say, we are focusing on filing a precedent with the FDA and soon after with European authorities, and that's really our priority. We will see for next year for what we serve as that.

Thank you, Jean-Paul. Thank you, Thibault, for the questions. Operator, do we have questions left? We have already passed the top of the hour.

We have one more question left. Are you happy to take it?

Yes, please.

Thank you very much.

Now we're going to take the last question on audio lines. And the question comes from the line of Susila Hernandez from Kempen.

Your line is open. Please ask a question.

Yes, thank you for taking my question. I have a question on PIVLAS. Looking at the number of patients treated in Japan doubling compared to June of this year, do you expect this trend to continue, and what kind of efforts will support this? Thank you.

Simon, do you want to take projections on that? Yeah, I mean, I won't provide numbers in terms of projections. The only thing I would say, I mean, clearly you can't expect this to be linear and every single quarter we're going to add 10% because we'll just get to an enormous market share in a matter of several quarters after launch. I think what we are seeing is a very, very nice uptake, which I think is also in part because obviously we've got trial centers and trialists that are familiar with the drug and adopting it quickly. We will also now obviously start to move into other physicians who we are talking to already and they are using. But that adoption probably is slightly slower than we're seeing amongst trialists, which is quite understandable and quite natural. But we have a sales force that is regularly calling on these people. It's a highly concentrated market. We have about 600 hospitals that account for most of the patients. And we do, we are anticipating revisions to the treatment of ASAH and vasospasm guidelines in the latter part of next year, I think all of which will be catalysts to continue the growth.

And maybe also what I would, maybe it's Jean-Paul, what I would add for Clazo is that what we see in Japan is a change of the way the patients are treated now People are using much less fluid. They are controlling blood pressure in a very different way than 10 years ago when we started to do these studies. And this will be very important, I think, for REACT, because I do believe that with the present treatment, the chances to see... a larger beneficial effect of Clazo in the REACT study are there. I think that, frankly, 10 years ago, the anesthesia, the intensive care treatment of these patients were not as good as today. So, I'm really looking forward to look at the REACT results.

Thank you, Jean-Paul. Thank you, Shaila. All right. I'm double-checking on the web for questions coming through the chat box. It seems that all of them have been addressed via questions being asked by the analysts. So, operator, I think I'll be closing down the lines now. So, thank you very much for having us on this call and your continued interest in Eidosia.