Idorsia Aktie

Good day, and thank you for standing by. Welcome to the Idorsia Half Year 2026 Financial Results Webcast and Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to our first speaker today, Kevin Boss. Please go ahead.

Thank you, Nadia. Good afternoon or good morning, everyone, and welcome to our half year 2026 investor webcast. My name is Kevin Boss, and I'm responsible for Investor Relations at Idorsia. Today, rather than simply reviewing what happened during the first 6 months of the year, we want to focus on what will drive the next phase of growth and value creation at Idorsia.

Joining me on the call, we have Jean-Paul Clozel, Chairman and Interim CEO; Benjamin Limal, Head of Europe and International Markets; Shal Jacobovitz, President of Idorsia U.S.; Martine Clozel, Chief Scientific Officer and Head of Research; Dominique Le Terrier, Global Commercial Strategy and New Product Planning; Amer Joseph, Chief Medical Officer and Head of Global Clinical Development; and Arno Groenewoud, our Chief Financial Officer. Each of them will take you through the progress being made across the business before joining the Q&A session.

Next slide. As always, today's presentation contains forward-looking statements that involve known and unknown risks, uncertainties and other factors that may cause actual results to differ materially from those expressed or implied by such statements.

With that, let me hand over to Jean-Paul. Next slide.

Hello, everyone. It's a pleasure to be with you today. Next slide. Let's start with a quick overview of top-line achievements. QUVIVIQ sales reached CHF 91 million, an increase of 62% year-on-year, and we remain well on track to reach our full year guidance. This performance reflects strong commercial momentum in Europe and Canada. In the United States, after resetting the business on a more efficient cost base, we are now seeing a return to growth. Benjamin and Shal will provide you more details in a few moments.

I'm also delighted that Roland Wandeler will join Idorsia as CEO on October 1. Finally, we significantly strengthened our financial position during the first half. Arno will come back to this and the guidance later in the presentation. During the first half 2026, we have built a strong foundation for a new phase of company growth. Together with the management team, we have defined 4 clear drivers of growth, which should fundamentally change the trajectory of the company.

Next slide, please. These are the 4 key drivers of growth that are guiding our priorities. First, maximizing the current QUVIVIQ opportunity in insomnia. Second, expanding the long-term value of daridorexant beyond insomnia. Third, unlocking the value of TRYVIO/JERAYGO. And fourth, continuing to advance a broad and innovative pipeline. The team on the call will go through these growth drivers one-by-one. Next slide.

Let me begin by explaining how we intend to maximize the sales of QUVIVIQ in insomnia. We will continue the growth momentum through geographic expansion, expanded market access, greater reach into primary care, innovative patient engagement initiative and continued improvement of our label, including data in pediatrics. Benjamin and Shal will cover the progress in the different regions, and then Martine will present some of the life cycle initiatives we have to reinforce differentiation.

Benjamin, please take us through Europe, Canada and other international markets. Next slide.

Thank you, Jean-Paul. Good morning, good afternoon. As you all know, nutrition, exercise and sleep are 3 fundamental pillars of health. And despite the enormous impact insomnia has on quality of life and overall health, there remains a significant unmet need for effective long-term treatment options. In Europe, QUVIVIQ is the only treatment specifically approved for the long-term treatment of insomnia disorder.

By targeting the overactive wake signaling, QUVIVIQ helps patients sleep without acting as a traditional sedative and with positive impact on the daytime functioning. Across Europe and Canada alone, we estimate the addressable market to exceed 5 billion standard units annually. This remains a very large opportunity, and we are still in the early stage of unlocking its potential.

Next slide, please. On top of the U.S., Idorsia has a presence and QUVIVIQ is available in 10 European countries and Canada. We plan to expand into the Benelux countries, Republic of Ireland, Norway, Denmark and Portugal. On the left-hand side, you see that the phased launch of QUVIVIQ is driving steady growth in our quarterly sales. 63 million tabs of QUVIVIQ have already been prescribed to patients in the EUCAN this year. Public and private reimbursement, rapid adoption by specialists, primarily psychiatrists and neurologists and increased awareness among general practitioners are the 3 drivers of our growth. France, Germany, the U.K. continue to be our largest European market and are driving a substantial portion of overall growth.

Next slide, please. QUVIVIQ is publicly reimbursed in these 3 markets, and the sleep medicine community has quickly recognized QUVIVIQ's innovative approach to treating patients with insomnia. European guidelines published end of 2023 also support the use of DORAs in the treatment of chronic insomnia. But insomnia is a condition primarily managed by primary care physicians in these 3 countries, ranging from 60% in Germany to 90% of the insomnia market in the U.K.

So by collaborating with Menarini to support the launch of QUVIVIQ to primary care physicians, we are accelerating awareness and adoption of the product in primary care. We have achieved a significant market share in France. We are experiencing a rapid growth in Germany, and we are entering into a phase of accelerated growth in the U.K. Almost 40% of specialists in Germany and France, 26% of French GPs and 13% of German GPs have adopted QUVIVIQ already. To put this into perspective, DORAs were first launched in Japan 10 years ago. And today, accounts for approximately 38% of the total insomnia market in Japan. So we believe Europe and Canada remains at a much earlier stage of adoption, creating significant room for future growth.

Next slide, please. We are also continuing to expand geographic reach. Our footprint now extends far beyond our directly commercialized markets. In the first half of '26, we've added strategic partnerships in Latin America and the Middle East, and we are close to agreeing a distribution partnership for Central and Eastern European markets. Of course, signing an agreement is only the beginning. The real value comes from successful execution in the market, and we look forward to working closely with our partners as these launches progress.

Next slide. You all know that especially in Europe and Canada, access remains an important driver. Public reimbursement has been secured in France, in Germany, the U.K. and Australia, while Canada and Switzerland benefit from broad private insurance coverage. Discussions to further expand publicly reimbursed access are ongoing in Spain, Canada and across the Nordic region. As already mentioned, we also plan to expand into the Benelux countries, Republic of Ireland, Norway, Denmark and Portugal.

Next, please. Co-promotion partnerships continue to extend QUVIVIQ's reach beyond the specialist prescribers. We saw the effect of the existing co-promotion agreement with the Menarini Group in France, Germany and the U.K., and we also have an agreement with Menarini in Switzerland. We have very recently entered into an additional co-promotion agreement with Viatris, which initially covers Italy and Canada. Idorsia has already been detailing GPs in Canada, but this agreement will significantly expand our reach and improve our share of voice in a competitive market. Together, these initiatives increase the addressable patient population, and I look forward to updating you on our progress at the full year result presentation.

With that, I'll hand over to Shal to provide an update on QUVIVIQ on the U.S. market. Shal?

We're pleased to present the U.S. performance with you today. Over the past 12 months, our commercial strategy has evolved. We have taken concrete steps to streamline execution across all spend to maximize revenue and profitability. We are systematically transforming how QUVIVIQ reaches, converts, retains patients, creating a more scalable, profitable growth model while strengthening our position in the insomnia drug -- in insomnia as drug of choice and the preferred DORA.

Next slide, please. Our strategy is built around 3 principles: disciplined investment and execution, focused engagement with high-value prescribers and profitable growth. We are allocating resources to physicians, accounts and patient populations where we see the greatest opportunity to create long-term value. At the same time, we continue to build advocacy for QUVIVIQ 50 milligram as the preferred insomnia treatment option that delivers on both night and daytime efficacy with a safety profile that is comparable to placebo. These actions are driving the next -- the return to growth that you'll see on the next slide.

Next slide, please. Looking to the future, one of our most important opportunity lies in maximizing value of the growing body of clinical evidence supporting QUVIVIQ. This is providing us the ability to further enhance the value proposition for payers and support efforts to drive profitable access. New and emerging data from pediatric development across areas such as menopause and nocturia continue to strengthen QUVIVIQ's differentiated profile.

We are incorporating the data into updated value proposition designed to better communicate the full clinical and economic value of QUVIVIQ to payers, providers and patients. We are initiating a new study designed to confirm the daytime functioning results previously observed with the 50 milligram dose in our Phase III program with the objective of supporting inclusion of these benefits in the U.S. product label. We are continuing to support the process to remove scheduling restrictions for the DORA class. The enhanced evidence package strengthens our ability to negotiate improved access, optimize rebate strategies and further differentiate QUVIVIQ from other DORAs and legacy insomnia therapies.

As access improves, we expect to unlock greater prescribing opportunities while simultaneously improving the profitability of each prescription written across our various payer types. Perhaps the most significant evolution in our commercial strategy is our focus on innovative patient access models, including direct-to-patient or DTP.

Next slide. We believe DTP is innovative with the potential to fundamentally revamp our patients' access to QUVIVIQ by creating a more seamless end-to-end fulfillment experience. By reducing friction in the patient journey, we expect to increase overall treatment initiation, lower the abandonment rates, improve patient experience and increase refill persistence rates over time.

Importantly, this model has the potential to substantially reduce patient acquisition costs while increasing patient lifetime value, improving both growth and profitability. We view DTP not simply as an access initiative, but it's a scalable commercial ecosystem that can expand reach, improve patient outcomes and create durable competitive advantage beyond the traditional model. We have completed the design phase and are well advanced in the platform build and with the objective of launching the pilot program in the coming weeks. Learnings from a successful execution will pave the way not only for scale up, but also open up ways of further expanding patient access.

Taken together, these initiatives will reflect a commercial organization that has evolved from optimizing the traditional model to building a next-generation growth platform. By combining differentiated clinical evidence, precision execution, stronger market access and innovative patient acquisition and retention capabilities, we believe QUVIVIQ is increasingly well positioned to accelerate profitable growth and strengthen its leadership in the insomnia market.

And with that, I will hand it over to Martine to take you through some of the life cycle initiatives we are pursuing with daridorexant.

Thank you, Jean-Paul. After many years of breakthrough research and publications around dual orexin, the team at Idorsia is now leveraging the differentiation of daridorexant by generating additional clinical evidence in order to widen and maximize its therapeutic potential.

Next slide, please. This begins with a broad portfolio of investigator-initiated and investigator-sponsored studies across multiple patient populations, some with insomnia, but also many investigator-sponsored studies beyond insomnia. For example, in Alzheimer's prevention in-persons with parents or siblings affected by Alzheimer's disease. A study to help smoking cessation, one in alcohol dependence to reduce craving for alcohol, one to enhance buprenorphine adherence to help treat opioid disorder, one with the Department of Defense to reduce post-traumatic stress disorder.

The slide shows those studies which are ongoing with the time line for data availability estimated based on the current patient recruitment status and study duration. We are also supporting a series of studies in additional areas currently in preparation, and we will update you on as they progress. Collectively, these studies have the potential to further strengthen the medical utility and differentiation as it is a very unique molecule of daridorexant across a broad range of patient populations.

Next slide, please. Of course, the key news just a few months ago was a positive study of daridorexant in pediatric insomnia. Remember, there are no medications approved for pediatric insomnia in the U.S. and daridorexant is the only DORA under pediatric investigation. The study enrolled 165 children aged from 10 up to less than 18, and importantly, included 87 children with neurodevelopmental disorders, attention-deficit hyperactivity disorder and autism spectrum disorder, either concerned of subthreshold traits. Overall, a group of patients with a very high prevalence of insomnia.

The study delivered outstanding Phase II results in children with insomnia disorder, demonstrating a statistically significant and dose-dependent increase in total sleep time, and clinically meaningful improvements across multiple sleep measures. Efficacy was particularly pronounced in children with insomnia and neurodevelopmental disorder. Very importantly, the excellent safety and tolerability profile of daridorexant was confirmed in these children, including at the highest adult recommended dose of 50 milligrams per day. Following these results, we are engaging with regulators to define the pathway toward the potential pediatric indication in insomnia. We are also preparing presentations and publications that will provide a more detailed review of the data and we look forward to sharing these results with the scientific community.

Next slide. The results from the pediatric study in addition suggest orexin signaling may play a broader role than just for treating insomnia in children with neurodevelopmental disorders. Here again, supporting Jean-Paul's introduction, we are expanding the long-term value of daridorexant beyond insomnia. To capitalize on these findings, a second clinical program for daridorexant in neurodevelopmental disorder beyond insomnia is being designed. This could open an entirely new therapeutic for patients with NDDs, another area of significant unmet need. We are currently refining the development strategy and look forward to sharing more details once the data are presented publicly and after discussions with health authorities.

Now I would like to hand over to Dominique Le Terrier, who will guide you through the third driver of growth, unlocking the value of aprocitentan. Dominique, please. Next slide.

Thank you, Martine. I'd like to take you through the third growth drivers, unlocking the value of aprocitentan marketed as TRYVIO in the United States and approved as JERAYGO across Europe, the United Kingdom, Switzerland and Canada. We believe these assets represent a significant commercial opportunity, and this is supported by a differentiated clinical profile with compelling efficacy and safety across the comorbid population, increasing physician awareness of the significant unmet need in difficult to control and resistant hypertension. It's also supported by a compelling clinical and economic value proposition that resonates with current patient population-based payer needs, but also and we'll come through this, a capital-efficient path to commercialization.

Next slide, please. So let's start with the opportunity. Based on our initial commercial presence and physician engagements at the leading hypertension centers in the U.S., interest in TRYVIO's profile is strong and real-world feedback continues to reinforce its differentiated clinical profile. TRYVIO/JERAYGO is the first and only therapy targeting the endothelin pathway approved for systemic hypertension. The endothelin pathway plays an important role in many patients with difficult to control and resistant hypertension, yet it is only aprocitentan that addresses this pathway.

As a result, TRYVIO/JERAYGO brings physicians a uniquely differentiated therapeutic approach. Importantly, TRYVIO and JERAYGO demonstrated double-digit reductions in systolic blood pressure in patients already receiving at least 3 antihypertensive therapies with the majority receiving 4 or more therapies and still hypertensive. We see this efficacy consistently across multiple comorbid patient populations, including patients with chronic kidney disease, obesity, diabetes, African American and elderly patients.

Equally important is the favorable tolerability profile. There is no potential for drug-drug interaction, which is important in these poly medicated patients and our U.S. product information includes just 2 adverse events, mild and transient peripheral edema and an expected decrease in hemoglobin from plasma volume expansion. Across the clinical program, we observed no evidence of hyperkalemia, no hypotension, and no hyponatremia, which together create a highly differentiated profile.

At the same time, physician awareness of difficult to control and resistant hypotension continues to increase. This growing focus on the significant unmet need in these patient populations is creating an increasingly favorable environment for launch. While pre-partnering discussions continue, we believe it is important to build on the initial momentum. The current environment presents a meaningful opportunity to establish market presence, generate experience and further demonstrate the value of aprocitentan.

Next slide. So to support this opportunity, we are discussing a dedicated financing structure with investor in Idorsia Investments SARL, the special purpose vehicle that owns the rights to aprocitentan. These investors have made an offer to provide financing to support launch and patient access initiatives based on a commercialization strategy centered on the co-promotion partnerships in the U.S. and in Europe. Consistent with this approach, we are currently engaged in discussions with potential co-promotion partners in both regions.

As currently envisaged, the financing would be fully backstopped by existing SPV investors, while all existing SPV noteholders will be offered the opportunity to participate on binding terms have been agreed under long-form documentation and subject to applicable approvals. The market for difficult-to-control and resistant hypertension is being actively developed, awareness is increasing and TRYVIO/JERAYGO has a differentiated profile that positions it well to benefit from this momentum. We believe the financing and co-promotion model currently under discussion would provide an efficient way to capture this opportunity without allocating capital from Idorsia.

I will now hand over to Amer, who will take you through the fourth growth driver, advancing of pipeline. Next slide.

Thank you very much, Dominique. I'm pleased to provide an update on our pipeline and the progress we continue to make across multiple programs. As you will see, we are advancing a broad portfolio using creative, focused, but also efficient development strategies designed to generate meaningful value inflection points.

Next slide, please. But before discussing the programs we're advancing directly, I'd like to remind you that 2 late-stage assets continue to progress under our partnership with Viatris. And based on the latest public update from Viatris, recruitment into the Phase III SOS-AMI study of selatogrel as a self-administered treatment of myocardial infarction is expected to complete later this year. And the 2 Phase III studies evaluating cenerimod in systemic lupus erythematosus are expected to report results in the first half of 2027. These are very important upcoming milestones and both assets continue to represent significant long-term value creation potential for Idorsia.

Next slide, please. Now let me turn to the programs we are advancing ourselves. So earlier this year, we reached agreement with regulators on the registration pathway for lucerastat as a monotherapy for all adult patients with Fabry disease, irrespective of mutation type or prior therapy. And since then, the team has made substantial progress preparing our development program, the first component being a pivotal kidney biopsy study, which is designed to demonstrate a reduction in renal Gb3 burden after 18 months of treatment. We expect to initiate the study in the third quarter of this year.

In parallel, we are advancing preparations for the second study, evaluating the transition from intravenous enzyme replacement therapy to oral lucerastat and looking at the impact on long-term renal function and other clinical parameters when compared to ERT. Together, these studies form the foundation of the registration program with potential regulatory filing as early as 2029, and this could position lucerastat as the first oral therapy suitable for all patients with Fabry disease.

Next slide, please. We now come to our Phase II proof-of-concept and proof-of-mechanism portfolio. Now the most advanced program is our first-in-class oral CCR6 receptor antagonist currently being evaluated in a proof-of-mechanism study in adult patients with psoriasis. Now this compound targets the Th17 pathway through a differentiated mechanism designed to selectively reduce pathogenic immune cell migration while still preserving systemic immune function. We designed the study to assess efficacy, dose response and safety in a well-characterized Th17-mediated disease. And a positive outcome would establish both proof-of-concept in psoriasis but also provide us with some mechanistic validation for potential expansion into multiple additional CCR6 and Th17-driven indications. Recruitment is now completed, and we expect data towards the end of the year.

Next slide, please. Our second immunology program is a first-in-class oral CXCR7 receptor antagonist being evaluated in progressive multiple sclerosis. Now this program represents a potentially unique opportunity in MS as it addresses one of the most significant unmet needs in the field, which is restoring neurological function through remyelination while simultaneously reducing neuroinflammation. Now of note, current therapies is largely focused on controlling inflammatory activity.

This study reflects our broader development philosophy, generate maximum insights while managing development risk efficiently. And this study has a very mechanistically rich study design with pioneering high-quality brain imaging, and we aim to demonstrate biological activity and obtain early evidence of therapeutic benefit within a relatively short treatment period. A positive outcome would establish CXCR7 as a novel therapeutic approach in MS. Recruitment is ongoing, and we expect results in the second quarter of 2028.

Next slide, please. Our third immunology program is the first-in-class oral CXCR3 receptor antagonist being developed for vitiligo. Now vitiligo is driven by recruitment of CD8 cells, T-cells into the skin through the CXCR3 pathway. And by blocking CXCR3, our compound is designed to interrupt the migration of these pathogenic T-cells that target and destroy melanocytes. Thereby, this addresses a fundamental disease mechanism, but still whilst we hope preserving systemic immune function. What makes this program particularly interesting is its differentiation from the current treatment landscape, which relies heavily on JAK inhibition, which is associated with a number of toxicities. Site initiation activities for the clinical trial are underway across the U.S. and Europe, and we expect recruitment to commence in the coming weeks. This proof-of-concept study is expected to generate results next year.

Next slide, please. And here, you see an overview of the pipeline. During the first half of the year, we also reported additional positive results from our synthetic glycan vaccine program targeting clostridium difficile infection. The Phase I data demonstrated a favorable safety profile and a clear dose-dependent increase in immune response with all participants in the high-dose cohort generating high antibody responses. Now these results further validate both the vaccine candidate, but also the broader synthetic glycan technology platform. And as a result, we have initiated partnering discussions to advance this program and potentially the platform more broadly.

Looking further ahead, our novel CFTR type-IV corrector in the treatment of cystic fibrosis, which has the potential for universal additivity with all other therapies targeting CFTR, remains on track to enter Phase I first-in-human studies later this year. This program is a prime example of the scientific innovation that continues to emerge from Idorsia, combining an Idorsia-discovered compound acting on an Idorsia-discovered binding site. So taken together, we believe that Idorsia has a differentiated innovative pipeline with opportunities in rare disease, immunology, neurology and vaccines with several value inflection points emerging over the near term and over the coming years.

And with that, I hand over to Arno. Next slide.

Thank you, Amer. Good afternoon, and good morning to everyone following on the call. Next slide, please. In my first slide, you can really see the continuous growth of our QUVIVIQ sales, which has been achieved with a flat OpEx. As a result, the non-GAAP operating loss, excluding one-off contract revenue, significantly reduced compared to H1 2025.

QUVIVIQ product sales, excluding partner sales, increased with 62% from CHF 56 million in the first half of '25 to CHF 91 million in H1 2026. The main driver of the sales increase is the EUCAN region, where sales increased from CHF 44 million to CHF 74 million. But at the same time, also the U.S. returned to growth. As explained earlier by Shal, due to various measures that were taken in 2025 and '26, the product sales increased from CHF 12 million in H1 '25 to CHF 17 million in H1 '26.

Further, the reported quarterly sales numbers for Q1 and Q2 are distorted by stocking. You may have seen that. And they do not really reflect the actual growth. But I can tell you that also on a quarter-by-quarter basis, the sales volume in Q2 increased with more than 20% compared to Q1, which demonstrates the continuous growth of QUVIVIQ sales. Non-GAAP contract revenue of CHF 8 million mainly includes upfront payments from our partners for QUVIVIQ licenses for Latin America and the Middle East. This all resulted in a non-GAAP EBIT loss of CHF 54 million.

Next slide, please. In addition to an outstanding operational performance in H1 '26, we were also able to successfully strengthen our financial position and access to liquidity. As you know, we started the year with CHF 89 million in cash. Operational cash inflows included CHF 97 million from QUVIVIQ product sales, including sales to partners and operational cash outflows included CHF 96 million of SG&A and CHF 45 million of R&D costs. The CHF 27 million other cash outflows mainly included working capital movements.

Further, as announced in June, we refinanced the short term new money facility with a longer-term loan from Pharmakon. As you may recall, at the time of the debt restructuring in 2025, the bondholders provided a short term new money facility for CHF 150 million to fund the ongoing operations, of which we had drawn already CHF 105 million. We have now refinanced that new money facility with a term loan from Pharmakon, which pushes out the maturity to June 2031.

On signing of the loan, the company received CHF 147 million, net of the cost in OID, which is mainly used to repay the new money facility for CHF 117 million, including the OID and accrued interest. This resulted in liquidity of CHF 89 million at the end of June 2026. In addition to that, we have access to a further CHF 100 million from the term loan as additional drawings, totaling CHF 189 million in liquidity available to Idorsia. All-in-all, a strong liquidity that puts us in a very good position to fund our activities leading to inflection points.

Next slide, please. This slide summarizes the maturities of our company's debt. The additional comments that I can give is that in Q2, J&J converted CHF 85 million of the outstanding convertible loan into 7.4 million Idorsia shares, which leaves a remaining loan of CHF 250 million that can be converted at any time into 21.7 million shares based on a conversion rate of CHF 11.48 per share. Any outstanding amount at maturity in June '27 can be converted at the same fixed conversion price of CHF 11.48 at the discretion of Idorsia, so will not result -- necessarily result in a cash out.

The debt notes held in Idorsia Investments SARL have a very long maturity, extending to 2048 or 2050, and are secured by assets held within the SPV, namely aprocitentan, selatogrel and cenerimod. These instruments are structured as pay-as-you-gain obligations, meaning repayment is linked to future cash flows generated by those assets rather than near term cash requirements for Idorsia. This means that with the refinancing of the new money facility by the term loan from Pharmakon, Idorsia has no near term cash relevant debt maturities.

Next slide, please. Based on our strong performance in the first half year of 2026, we are well on track to reach our target sales of CHF 200 million and a non-GAAP EBIT of CHF 120 million. And therefore, we reaffirm our 2026 guidance.

And with that, I hand back to Jean-Paul. Next slide, please.

Thank you, Arno. I would like to conclude where we began. We all believe that Idorsia has significant untapped value and this will need to focus on our 4 key drivers: maximizing QUVIVIQ in insomnia, expanding the long-term value of daridorexant beyond insomnia, unlocking the value of TRYVIO/JERAYGO and advancing innovation across our pipeline.

Looking ahead, our focus will be on execution. And of course, the execution will be led by Roland. I am very much looking forward to handing over the leadership of the company to him later this year. Roland combines scientific expertise with exceptional commercial experience. He has worked across both large pharmaceutical companies and entrepreneurial biotech organizations in local as well as global leadership roles. I am convinced he is ideally suited to lead Idorsia through its next phase of development. Thank you for your time, your continued interest and your support.

Kevin, over to you for questions. Next slide.

Thank you, Jean-Paul. Thank you, everyone. Now we have time to take your questions. So operator, please open the lines for the Q&A.

[Operator Instructions] And the first question comes from the line of Kate Farrelly from Deutsche Bank.

This is Kate Farrelly from Deutsche Bank. Firstly, on QUVIVIQ on the direct patient launch, what's the expected uptake here? And is this included in the CHF 200 million guidance? And secondly, if you don't mind, on TRYVIO on the SPV financing offer, what's the expected timing to the binding terms? And what does the size and structure need to look like to fund a launch without Idorsia capital? And then just to double check, the co-promotion partner is a precondition for this launch and you wouldn't go ahead alone with just the SPV financing?

Thank you very much, Kate. Shal, do you want to take the first question on DTP?

Yes. Right now, remember, we are launching a pilot program, which will last between now and the end of the year. Once we get the results of the pilot program to see how effective it was, what needs to be adjusted, we'll have better guidance on any return of the DTP program.

Thank you, Shal. And Dominique on TRYVIO?

First, I will respond to the co-promotion, I mean, piece of the question. So we are currently discussions -- very active discussions with co-promotion partner. But at this stage, it's not possible to disclose anything as we don't have finalized that. So it will come a bit later. On the financing, maybe Arno.

Yes, about the time line. We are negotiating now or do the final negotiations with the funding partners and the co-promotion partners. And as soon as we have signed agreements, we will, of course, let you know.

And now we're taking the question from Sushila Hernandez from Van Lanschot Kempen.

This is Anna for Sushila. This is on QUVIVIQ and expanding the reach into primary care. Could you provide a bit more color and on how many primary care physicians are currently prescribing for chronic insomnia also specifically DORAs? And could you elaborate on your strategy to expand your reach into primary care?

Thank you. Benjamin?

Yes. I'll take this question. Thank you for the question. So the strategy is really to go with partners, co-promotion partners to reach out to GP and to primary care. So we have already an established relationship with -- and partnership with Menarini in 4 markets in France, in Germany, in the U.K. and in Switzerland.

In France, we see that already 26% of the GPs have started using QUVIVIQ, when 13% of the GPs in Germany already prescribed QUVIVIQ. We don't have yet the numbers in the U.K. and Switzerland because we just started the collaboration, the partnership in these 2 markets. We are entering into a new partnership, partnership that we just announced this morning with Viatris, who is going to detail QUVIVIQ to GPs in Italy and in Canada. At this stage, we did not have any promotion to GPs in Italy. So it's really new, when we already had some promotion to GPs in Canada, but we are expanding our share of voice through this collaboration with Viatris.

Does that answer your question?

Yes. Perfect. And if I can squeeze another in. This is also on QUVIVIQ for the DTP. How long could it take from reaching a patient through advertisement to treatment prescribed and home delivery? And would there be any review of treatment at 6 months?

Shal, do you want to take this one?

Sure. So right now, the way the system is set up, the flow-through really depends on the type of insurance that the patient has in terms of time end-to-end. But acquiring a patient, having them see -- having them speak to a healthcare professional is the quickest part of the process. That can take minutes. The next phase, when it goes to the dispensing pharmacy, the online pharmacy, that can take a little while to sort out the insurance. But we expect that the average patient should be able to go through the entire process within 25 days.

And the question comes from the line of Raghuram Selvaraju from H.C. Wainwright & Co.

Firstly, on daridorexant, I was wondering if you could comment on what you expect the effective dosage range to be for daridorexant in applications beyond insomnia and how you are thinking about prioritizing these indications, particularly from the perspective of adolescents and children versus adult indications? That's the first question. And then the second pertains to whether you can give us a broader update on the current status of the Viatris collaboration, particularly with respect to ongoing clinical development activities with selatogrel and cenerimod? And also just give us a sense of what the remaining financial obligations are for Idorsia under the terms of this agreement?

Thank you, Ram. Martine, do you want to take the question on the NDDs development for daridorexant? Martine, are you there? Otherwise we hand to Arno.

Yes. So we are working currently on that and planning discussions with health authorities.

Yes. As Martine has said, this is Arno. So we are evaluating the correct dose range. What could be applicable insomnia, of course, maybe not applicable in NDDs, but this is a careful discussion internally with experts and also regulatory bodies. So we can't comment on the dose ranging at this point in NDDs or other indications beyond insomnia.

You also want to take the next question on the Viatris collaboration then, over to Arno for the financials.

What was the first?

The first question was on the collaboration. They want more details on the development and the collaboration with Viatris.

Okay. Yes. So with the collaboration with Viatris, Viatris are taking really the lead on all activities from a clinical study perspective. And they're involving us in updates and safety updates, but they are really taking the full sponsorship role on both of these assets. Yes. And then on the financial commitments, we have a fixed cost-sharing obligation for 2026 and the total amount for this year was about CHF 25 million, of which we already paid half. So roughly CHF 12.5 million needs to be paid in the rest of the year. And that's the end of our financial obligations. After that, there will just be milestones and royalties that could come from the contract.

Okay.

Does that answer your question, Ram?

Yes.

And now we're going to take our next question, and it comes from the line of Joris Zimmermann from Octavian.

This is Joris Zimmermann from Octavian. Congratulations to the whole Idorsia team on the H1 achievements. And 2 questions, if I may. So firstly, I wanted to come back to this potential new financing from bondholders or noteholders in the SPV. Can you share the magnitude of amount or the expected magnitude of amount for those co-promotion launch activities? And then also, what does this mean for a potential aprocitentan licensing partner? Would that mean that the partner takes over this co-promotion agreement? Or could this partner then stop it again?

And the second question would be on the development plans for QUVIVIQ in neurodevelopmental disorders. Am I correct to assume that you look at both indications, ADHD and autism? And then based on the current or the existing Phase II data that you already have, do you expect a shortened or accelerated pathway to potential approval?

Thank you very much, Joris. Dominique, do you want to take the first 2 questions on TRYVIO?

Yes. So regarding the financing, I think it's a bit premature to give the magnitude of the investment and the numbers at this stage as we have active discussions here as well with the different investors. Regarding the partnering discussions, I think we still have partnering discussions. And while partnering discussions continue, we believe it is important not to lose the momentum and making sure that we can also tap the current environment, which presents a meaningful opportunity to establish market presence. So that's also why at the same time, in parallel, we activated these 2 approaches.

And Joris, maybe to add to that, I think you need to think about a significant amount that would allow us to really properly launch the drug and make the most of the potential of the drug. So I think that will be important to understand.

And then over to Amer for ADHD, autism and accelerated approval possibilities.

Thank you. So at this stage, we cannot comment on which specific neurodevelopment disease we will be evaluating further. We are carefully looking at the Phase II data with external experts and regulatory bodies to help contribute that decision. Further, again, we are looking at different scenarios on how rapidly we can accelerate the development in NDDs with QUVIVIQ. So this is clearly an avenue that we want to explore different designations with the FDA in order to accelerate development as much as possible.

Does that answer your questions, Joris?

Yes. Perfect.

Nadia, are there any further questions?

There are no questions at this moment. [Operator Instructions] Okay. And now we're going to take our last question for today. And it comes from the line of Joris Zimmermann from Octavian.

Very short question on cash and cash reach. So you stated that you have the CHF 89 million currently in the banks. There is CHF 100 million remaining from the Pharmakon loan. Can you confirm the previously communicated 2028 cash reach time line?

No. Joris. No. You're absolutely right. I mean with this cash and the undrawn facility, we have a cash runway that brings us into 2028.

Thank you, Joris, for your questions. I think this concludes our call for today. Thank you, everyone, for your time. Next schedules on our event calendar is the first quarter results on October 29, and we will also be present at several upcoming healthcare conferences in the near future. So we hope to get the opportunity to speak to more of you shortly. Operator, please close the lines.

This concludes today's conference call. Thank you for participating. You may now all disconnect. Have a nice day.

Good day, and thank you for standing by. Welcome to the Idorsia Pharmaceuticals Daridorexant Pediatric Insomnia Results Conference Call. [Operator Instructions] Please be advised today's conference is being recorded.

I would now like to hand the conference over to your first speaker today, Kevin Boss. Please go ahead.

Thank you, Nadia. Good afternoon, and good morning, everyone, and welcome to today's webcast. We are here to discuss the positive results of the Phase II study of daridorexant for children with insomnia disorder, which we announced yesterday. On the call today, we have Jean-Paul Clozel, Chairman of the Board and Interim CEO of Idorsia; Martine Clozel, our Chief Scientific Officer and Head of Research; and Alberto Gimona, Head of Global Clinical Development and Medical Affairs. They will provide context on our daridorexant program and walk you through the key results from the pediatric study. Following their remarks, we will be happy to take your questions.

Next slide. The information presented today contains forward-looking statements. You have therefore been appropriately warned about the risks and opportunities associated with investing in Idorsia. Importantly, to today's presentation, daridorexant for pediatric use is investigational and not approved or marketed in any country. Next slide.

With that, I'll hand over to Jean-Paul.

Good morning, good afternoon to all. I am very happy to have the opportunity to join the call today and share some very exciting results. While we still have a lot of work to do in order to analyze the wealth of data generated, the top line results are very impressive. I hope you understand that we will share the detailed results at upcoming congresses and in peer-reviewed publication. To be able to protect publication in top-tier journals, we have to restrict what we share today. I am sure that you will agree with me that these results are very exciting. And I think what I also wanted to emphasize is that the fact that these fantastic results are really due to the very specific properties of daridorexant, which was chosen after synthesizing more than 25,000 products. And Martine will explain to you why this drug is so different and so exciting.

Next slide, please. In this study of 165 children suffering from chronic insomnia with or without neurodevelopmental disorder, we see a major improvement of sleep, particularly in those children with neurodevelopmental disorders. This alone is exciting. But beyond insomnia, the data suggests that orexin may play a broader role in children with neurodevelopmental disorders, potentially opening an entirely new therapeutic avenue for these patients.

Next slide. We understand since [ Sakurai ] in 2007 that orexin, which is produced by only a very small number of cells in the brain is a central player in wakefulness. The very same year, we published in Nature Medicine that dual orexin has receptor antagonist, which we call DORA, induce sleep and a very good quality of sleep. Now we know that insomnia is characterized by another active wake signaling. And that DORA's are a very good way of treating insomia to inhibit the [ overactive wake signal ] by blocking the 2 orexin receptors instead of depressing the brain to induce artificial sleep as most older drugs in insomnia were doing.

Next slide, please. But not all antagonist of the orexin system are created equal. We have worked relentlessly, even stopping the development of our first dual orexin to arrive at the optimal molecule. As Jean-Paul was telling, after 25 years of research, more than 25,000 molecules designed and synthesized are dual orexin and guided by the revolutionary work of computer modeling, we achieved what we were aiming for in our drug discovery and data. An antagonist of both orexin-1 and orexin-2 receptor, blocking both receptors with equal potency. With the rapid onset of action and the duration of action long enough to cover the night, but short enough to be divide of carryover effect even at the optimal dose for sleep. That's the best possible profile for a sleep drug. By that research goal, we wanted to avoid the pitfalls of molecules for insomia with suboptimal and too long pharmacokinetics, giving either the risk of carryover some somnolence in the morning or a sub-optimal efficacy when trying to avoid the disturbing risk of morning and daytime insomnolence by reducing the dose. QUVIVIQ has basically the perfect profile. As we can see on the right of this slide, fast absorption, fast decline and no accumulation over time.

Next slide, please. Daridorexant, QUVIVIQ, really surpassed our expectations in adults with insomnia both on efficacy and on safety. It is an extremely effective drug, within adults, 1 hour more of more of sleep at night, improving both sleep induction and the maintenance of sleep, giving also a better quality of sleep, restoration of a physiological sleep pattern with, in particular, more sleep. Daridorexant works in all periods of the night with the largest efficacy in the fourth quarter of the night.

Next slide, please. And yet, when we were checking if there was any carryover effect in the morning, there was none. The highest dose here in green of 50 milligrams per night did not induce sleepiness in the morning. To the contrary, thanks to the much better night and the exceptional pharmacokinetic profile of daridorexant, morning alertness was improved at 50 milligrams.

Next slide. I believe that the better night sleep in combination with no residual somnolence and the equilibrated antagonism of both orexin receptor is 50-milligram also improves the daytime functioning so well. Using the insomnia daytime symptoms and impact questioner, so-called [indiscernible]. We found that QUVIVIQ 50 milligrams improved all 3 domains: sleepiness; alert cognition; and mood and all the 14 questions of those domains with an increasing effect over time. This makes QUVIVIQ the only therapy to demonstrate significant improvement in data and functioning in patients with insomnia.

Next slide, please. Finally, as already mentioned, a very good safety and tolerability after chronic daily repeated administration, even on very long term.

Next slide. You will now see that once again, we are impressed by what this molecule brings this time to children with chronic insomnia as young as 10 years of age. The burden of chronic insomnia is substantial, especially in children with neurodevelopmental disorders, such as autism spectrum disorder, or ASD, and attention-deficit/hyperactivity disorder or ADHD. It profoundly effect the quality of life of both the child and the family, yet there is currently no FDA-approved medication for pediatric insomnia in the United States.

Alberto will now take you through the study design and these very important results. Alberto, next slide, please.

Hello. Thanks, Martine. Dear all, I'm happy to present to you the results of daridorexant study in children. As a note, I think Idorsia was the first company to start the program in children with the DORA. And given the daridorexant properties that Martine has just described, we actually were very eager to negotiate a program [indiscernible], and we did it with FDA and PDCO, with EMA. But first of all, let me thank the investigators together with the children, the caregivers who invested time to advance the science. And I'm happy to say that their time and effort was eventually very well awarded.

Next slide, Slide 13. In this slide, you see the study design is a double-blind, placebo-controlled dose-finding study, where children were randomized to 3 doses. Please note, these are the same doses studied in adult, 10, 25 and 50 milligrams. The children, the parents had the burden of spending 3 nights, 2 at screening and 1 on day 1 at the sleep lab to undergo polysomnography, from which the primary endpoint was derived. And this is an important feature of the study is polysomnography and 3 cumbersome nights, but the children and their caregivers did it. One question you may see on the slide is that on day 1, the primary endpoint is measured. So it's baseline to night in sleep lab, day 1, there is a sleep lab, again. But why on day 1 and not at the end. Indeed, because health authorities were concerned about the discontinuation rate in children, particularly with those nights at the sleep lab. So they wanted to minimize the risk of missed data points by getting the primary endpoint as early as possible during treatment. And actually, this was probably driven by the experience they had with previous studies. But indeed, in our study, we have only 1 child that did not remain in the study until the end of the treatment period, giving the first hint that the drug was very well tolerated and actually, they indeed like the drug because they continue to stay in the study.

Next slide, please, Slide 14. So as mentioned, the primary objective was the valuation of the total sleep time by polysomnography. Again, the study investigated 3 different dose, and the main point is the dose report -- the evaluation of the dose response instead of the [ per ways ] comparison to placebo. The study was sized to show those response.

Next slide, Slide 15. And here, you see the stratification in the study, which is an important innovative feature of this study that I'm proud we were able to negotiate with the health authorities. In effect, that include patients or children with narrow development disorders as well as children without comorbidities. And again, this was done to accommodate both EMA and FDA. In the middle, there is also a group of patients with subthreshold ADHD ASD, which means that they did were not diagnosis, but at screening, we have tools, recognized tool to screen for symptoms in size of ADHD and ASD, and they did not meet the formal definition. Eventually, we were able to agree with both FDA and [indiscernible] that those response was evaluated under overall mixed population.

Next slide, Slide 16. You see the demographic characteristics in this slide. And interestingly, there was 20% of children were down -- with age 10 and 11, which, in my opinion, honestly, is a great -- was a great achievement by the study team in considering and the investigator as well to convince the parents or the caregivers and the children to stay in the sleep lab for 3 nights. Another interesting feature is that we have 50-50 split between males and females. It's slightly different to the adult population where we have approximately 2/3 women and 1/3 man. The body weight is represented at the bottom of the slide, and you see that this expect -- as expected in this population. But actually, I would like to draw the attention, it's nothing to do with the study. But indeed, you see that the range of body weight were exceeding 100 kilograms for children in all treatment groups. So there is overweight and obese children in line with the increasing burden of this disease also in the pediatric population.

Next slide, Slide 17. Baseline disease characteristics, the average time from the diagnosis of insomnia was approximately 4 years. And you see the 3 characteristics that define insomnia and they are difficult to get to sleep and maintain a sleep during night that were reported basically by all children. And actually, early morning awakening was a little bit less represented. But the most important feature of this slide for me is the fact that, as mentioned, we had already 30% of children with the diagnosis of autism spectrum disorder and ADHD, attention-deficit hyperactive disease. On top of this 30%, there was an additional 20% with subthreshold ADHD and ASD, meaning patients with -- children with feature symptoms but didn't meet the diagnostic.

Next slide, Slide 18. I'm happy and proud to share that the study was successful and highly statistically significant dose response was observed. You see the p-value over there. In this study against the first regulatory study with DORA in children. Importantly, and the different versus placebo, at the high dose, the 50-milligram high dose with even nominally statistically significant difference from placebo. Again, this was not a requirement of the study, but the effects of so strong that we had also a statistical significance there. But further, the effect was particularly impressive. Actually, I would say with -- I haven't seen it earlier on with unprecedented increase in TST versus placebo in children with neurodevelopment disorders. Of course, this is -- we should be still be cautious because this is a dose finding study. But really, the results you will see when we publish are impressive. Let me say that there are still so many data that we need to analyze and properly interpret that we cannot say more. But -- while any conclusion cannot be drawn, I'm really excited about what we have seen beyond sleep. Here is a total sleep time, but we have other measures in children with the neurodevelopment disorder, that actually surprised me and excite me, and we are going to further analyze to put into a very nice publication that shows -- this data show that we may have potential impact on the disease itself and not just on insomnia.

Next slide. Slide 19. I This, for the moment, what was already is -- a great achievement here of this study is that we can say already that the safety profile at the same dose tested in adults. So we have children with the body weight. I mentioned the high range, but I would also like to mention the lower range, which was about 28 to 30 kilos, even the highest dose 50-milligram was well tolerated and actually, there is no dose response on any adverse event, but also similar to what we have observed in adults also on event -- events of special interest such as excessive daytime sleepiness, suicidality or drag abuse potential, all adjudicated blindly by an independent panel. The word here, why we adjudicate some events by a panel because we don't want to miss any signal. And here, again, shows and make it robust to the fact that we did not see any dose response of any of these events and especially no event at all most of these categories, including drug abuse.

Next slide, Slide 20. It's a very boring slide. And I will say thanks to whoever, but there is nothing here. Nothing really relevant when looking at adverse events reported by the children. And then you see all the adverse event reported in the population are in 1 table, which is quite exceptional. And you can see notice for -- and reaching to what Martine said earlier on. So we have very few adverse event 1 to 3 patients across group, including placebo, with somnolence and fatigue, which is the -- what we usually review when we look at the data in insomnia. Again here, no dose response. So eventually, the weight tolerability and safety to file observed in the adults seems concern -- confirming children. Again, same exact as [indiscernible].

Next slide. Slide 21. You have seen earlier the morning sleepiness, or actually, the name is not really reflecting what it measure. Actually, it's morning alertness reporting in adult population. Again here, we showed a similar measure in children. Again, the green bar is daridorexant at top of those and the blue is placebo. On top, you see the baseline and you see at week 2 after only 2 weeks, you observed that an increase in -- versus baseline of daridorexant 50-milligram and also an increase versus placebo. Again, the highest dose, we do not observe any sleepiness in the morning, rather a better, more refreshed pediatric population. And you see the scale from 0 goes from extremely tired to 100 [indiscernible].

Next slide, Slide 22, which is going to be my last slide. So with this data, what are the next steps. First of all, I'm looking forward to discussing this data with the health authorities, the PEDCO for EMA and the FDA to agree on a path forward to bring daridorexant into the children with chronic insomnia. We have, as some of you may remember, we have a bit in Europe, and we need to discuss also with EMA, the optimal path forward for the younger children cohort at -- below 10 years of age from 4 years to 10 years. This is what is summarized on the left of the slide. But equally, actually and really more exciting, we need to fully evaluate the surprising results that we see in NDDS, neurodevelopment disorder subgroups and then discuss with the health authorities about the potential program from children with NDDS beyond the treatment on this insomnia. But maybe here, the most relevant part, already immediate relevant part is that actually, this data is also relevant for adults. Insomnia is a -- we have a broad indication for insomnia in the U.S. and in Europe. And there are already many millions of patients with ADHD or ASD in the population in the U.S.

With that, I will hand back to Jean-Paul with the next slide, Slide 23. To you, Jean-Paul.

Thank you, Martine. Thank you, Alberto. I have to say that I'm really very happy when I see these results because Idorsia went through difficult times, and really, I want to thank all the collaborators, all the Board members, everybody who stayed. Without them, without this perseverance, we would not see today this data which in my mind will -- and you will see after the publication really represents a scientific breakthrough. These results show once again that daridorexant is an outstanding drug and they present a great opportunity for Idorsia. First, the clean safety and tolerability profile in children as young as 10 will undoubtedly strengthen confidence in QUVIVIQ among prescribers treating adults. Second, our continued development in the pediatric population should influence the descheduling process with the FDA and DEA.

Third, the unmet medical need in pediatric insomnia is substantial. Millions of children experienced chronic insomnia that profoundly affects daytime functioning, mood and cognitive and physical development. Remember, daridorexant is the only DORA currently being investigated in the pediatric population, positioning it to become not only best-in-class for adults, but potentially first-in-class for children.

Finally, the emerging data on neurodevelopmental disorder could unlock an entirely new therapeutic domain for daridorexant beyond insomnia. And we look forward to initiate discussion with health authorities on the data. As soon as we secure presentation at the high-impact congress and scientific publication in a high ranking journal, we can go, and we will go into more detail.

Many thanks, Jean-Paul. With that, Nadia, I think we can open the lines for questions.

[Operator Instructions] And now we are going to take our first question, and it comes to line of am Raghuram Selvaraju from H.C. Wainwright & Co.

Congratulations on this very exciting data. I was wondering if you could provide us with some additional granularity regarding what's the scope and nature of clinical development for a drug like daridorexant might look like, in the context of neurodevelopmental disorders, particularly autism spectrum disorder and how the efficacy endpoints in such a context might change relative to what you would typically use like total sleep time, for example, in the insomnia setting specifically.

And also, if you could give us some additional data on how the market opportunity, the total addressable market could change for daridorexant if it were granted an official label some years down the line, for example, in neurodevelopmental disorders, including but not limited to autism spectrum disorder.

Thank you, Ram. Maybe, Alberto, you take the first question, and then we hand over to Jean-Paul for the second question.

Yes, of course. I think as we will -- it's too early to look at what is the development plan that could be in neurodevelopment disorders, autism ADHD. Of course, the main hypothesis is emerging is that, okay, there is no doubt, this is my personal opinion, there is an effect in insomnia in this population. However, the new program will not look at insomnia in patients with neurodevelopment disorder rather potentially bringing the treatment of the disease is what also Martine was alluding to. And in that case, of course, the endpoint will be different compared to what we have now with TST or other measures of insomnia. So we will -- we may target directly the disease. And we have -- basically there are some scales that we can use and can be discussed with the health authorities. There is an EMA guidance, for example, on autism. so I'm not sure that the answer completed the first question. Kevin, tell me if I missed something.

That's fine. Thanks, Alberto. Then we can address the second question, Jean-Paul.

Yes. I think I have some numbers. I'm not speaking about commercial market, but the clinical need. I was turned first in adults. And as Alberto said, these adults today with insomnia can be treated with daridorexant. There is no exclusion from these patients. And I wa stunned done by looking that there are about 15 million adults with attention deficit disorders and about 25 to -- up to 50% of them have insomnia. So 7 million, if you want an average. 7 million of patients with ADHD, adults with insomnia. With intellectual disability or development disorders, 2.3 million adults with 85% prevalence of insomnia. And in autism, it's 5 million adults with autism today, and I would say, from 32% to 72% according to the publication. So about 50%, let's say, as an average, have, insomnia. So this is, frankly, a stunning number in adults. Now in children, of course, and I'm just speaking about the U.S., and I think that you could about -- multiply, have the same numbers in Europe. But focusing on the U.S., there are, in children, 5 million children with attention deficit -- or sorry, with hyperactivity and 25% to 50% of them have insomnia. There is -- there were 9 million children with intellectual disability. And they nearly are -- 90% have insomnia. And autistic children, there are about 2 million children. And I would say a majority of them have insomnia. So you see that -- even if we would take insomnia alone, there is a huge market in the U.S., and this is why I'm focusing on the U.S. number because there is no treatment today. So you see that there is a very big number of adults and children within insomnia, but also, of course, without insomnia. And as we mentioned, now we are going to really evaluate and certainly initiate a program in these patients with MDD. So I hope I answered the question.

I think you're on point, Jean-Paul.

Please, go ahead, Ram?

Yes. Sorry. I Just wanted to point out that as many in the audience may already know, autism spectrum disorder is growing at an unprecedented rate among neurodevelopmental disorders. And by some estimates, has increased by 175% in pediatric patients over the course of the past 2 decades. So I think that's an important thing to note. Two other very quick items I wanted to touch upon, if I may. One is with respect to whether or not you intend to seek additional prosecution of further patent claims around daridorexant to broaden the IP estate based on the observations that were made from the Phase II pediatric insomnia trial. And the other is from a competitive landscape perspective. If we look at the DORA class, and the unique attributes of daridorexant from a safety and tolerability perspective, is it your view and your expectation that because daridorexant seems to be uniquely safe and well tolerated, particularly for use in children as this Phase II trial showed that this might erect a competitive moat around it that will enable it and it alone to be applied in the pediatric setting and in the neurodevelopmental disorder context. Whether or not its ultimate activity lies solely in the domain of improving sleep or extends to other efficacy parameters.

So we -- we certainly have very unique properties by having this optimal pharmacokinetics and the data on -- data and functioning in adults are very, very compelling. And you see now -- you have only a glimpse of the results we are progressively discovering in the pediatric study, but we see this dose-dependent increase or increase at the highest dose, which is quite really surprising both in adults and now in children of an increase in morning alertness. And I think that we have really a perfect profile for children, and the safety and tolerability, which as you have seen are amazing, including a total absence of signs of abuse or withdrawal or addictive signs. So we have really a drug which is really perfectly suited for children and the result in sleep and [indiscernible]. So yes, of course, we are serving and taking care of the protection of the data, absolutely.

Yes. We have worked very actively on protecting this data. Of course, that's something which is key, and we have all the -- we have been active in the coming -- in the last weeks to really protect this new data. What I wanted to say that we had daridorexant, and we knew that we had an active drug, but we did not have the ideal drug. As Martine said, it took us 10 years and 25,000 new drugs in order to discover daridorexant. And it's only because daridorexant has it's unique pharmacokinetic properties, it's unique binding that we can achieve this data. It was really worthwhile to wait 10 years to work so hard for the chemist to get there. And I really believe that without these properties, it will be extremely difficult to go in children, for example, of a very low weight or to avoid the somnolence in the morning because of the pharmacokinetic characteristics that you need to get to this profile.

Maybe -- Alberto here. If I can add 2 words actually, I think in the competitiveness, I think that we have -- given what Jean-Paul and Martine has said, I can just add that from a development perspective, we are the -- in the adults and now it seems to be confirming children that it's the only one with a dose response on efficacy and no dose response on safety. And that can be seen easily in the FDA reviews of the data, and we have done exactly the same analysis with daridorexant that they did for lemborexant, for example. And actually, we were able to demonstrate that we don't have a dose response on safety. That's why they translate clinically the profile that Martine and Jean-Paul were highlighting from a scientific perspective. Sorry, just a comment.

Thank you, Ram, for your comments. Nadia, next question.

And the next question comes line of Joris Zimmermann from Octavian.

Joris Zimmermann from octavian. I have a follow-up question on the regulatory path forward. You mentioned that for the neurodevelopmental disorders, it might be a bit early, but I was wondering if you could share the expected next steps in terms of the general pediatric insomnia patient population? Or if my understanding here is indeed correct that you pursued the 2 indications independently? And if so, what your expectations are around the needed trials, time lines and if possible, already on the costs?

And then second question on the potential. I was wondering how do you assess the potential from the pediatric indication versus the potential that you could see from the potential halo into the adult population?

Thank Great. Thanks, Joris. Alberto, do you want to take the first question?

Absolutely. Again, as I mentioned earlier, it's too early. But indeed, the next steps will be to discuss with the health authorities. So for -- and you're right, we may -- we will -- need to pursue general insomnia, and with the data that we have in Phase II, although the data being so good that maybe we can discuss what are the further steps. But certainly, the bottom line is to get an agreement on path forward from both health authorities, with the minimize -- the idea is to minimize the number of patients or studies to be done. And the NDD is completely different -- separate. Again, we are not targeting NDD insomnia in those patients in those children, rather the symptoms or the feature of their disease. And for that, we need to get discussion. Again, there are only -- we are guided only by the guidelines for EMA at this point. And -- but we -- and there is no guideline from the FDA. So again, we need to use certainly specific scales and endpoints that are validated in for autism and then see what kind of studies the authorities request us to do. Again, I didn't answer very [ quick ], and I'm not answering about cost or time lines at this point because it's really too premature.

To answer your question on the repercussion for adults, I think, we have really a duplication or a replication of the amazing efficacy and safety profile in children. We knew daridorexant efficacy and safety at the same doses without dose adaptation in elderly, we are learning progressively that in patients with nocturia, as published, the efficacy on sleep also was replicated. Every time we are reproducing that this children study at the same doses as in adults with the amazing efficacy on sleep, particularly in the neurodevelopmental disorder subgroup are very, very impressive. And for that, I think, yes, it repercussion in the understanding of the potential in [ adult guideline ].

For the halo effect, how do we quantify. It's -- I would not be quantitative, but maybe qualitative. I think that what this data bring, if you can tell to a doctor that the really high dose, the higher dose, which can be -- which is allowed in adults has been given to children of 10 years old without any problem, I think it will convince them that this drug should really be safe in adults, I'm speaking. And really, you know that sleep drugs have always got a negative value because up to now, they had all side effects. So I think it's really going to help the marketing of today daridorexant in adults. But maybe the most important halo effect in adults with neurodevelopmental disorders because I think that when this data will be presented, you will understand why -- frankly, there would be only 1 drug to give to this patient when you see our data, and this is daridorexant. So -- and here, we are completely covered by the present label, both in the U.S. and Europe. So the halo effect for me, the most important is adults with neurodevelopmental disorders.

Thank you, Jean-Paul. Nadia, next question?

And the question comes from line of Sushila Hernandez from [indiscernible] Kempen.

This is [ Samreen ] on for Sushila. Congrats on the results. So first of all, I would like to go a bit more into your -- yes, the market that you were addressing. So how many of these 10% to 30% of U.S. children and adolescents that are impacted by insomnia do you aim to target actually? And which segment in the children -- in that market do you think would benefit the most?

And also a bit more on the future. So again, you said the financing is still preliminary, but can you tell us anything on whether the company feels sufficiently financed to conduct an extra study in pediatrics? And could you maybe expand a little on your current capital allocation priorities?

Thanks for the question. Jean-Paul.

I'm just saying that it's a little bit different between Europe and the U.S. for the children, I think that there are a lot of patients with insomnia -- children within insomnia in the U.S. who are treated. And this is not as a big number in Europe. So the market is certainly much bigger in the U.S. And I think that we have not really -- we have just got the results, and I would not be able to guide you on the potential market, but it is very big. And I think that if we consider is in the U.S., it's very big. Of course, neurodevelopmental disorders is also a very big market, but we need to do additional studies. And -- but I really -- when you speak about the cost of this study, first, these studies are just a questionnaire. This is not like many in many studies where you really need a CT scan, MRI, very expensive. Here, it's simple -- it is going to be a simple questionnaire and observation by the doctors, by the parents, by the caregivers. So these are not very expensive studies as you could imagine in other neurological problems. That's number one. The number two, I really hope that this halo effect that everybody believes is going to happen, we'll pay for it.

Nadia, next question.

And the question comes line of Justine Telliez from Kepler Chevron.

Congrats on this promising data. One follow-up question again, please, coming back on the potential program you aim to initiate in NDD patients. Could you please elaborate on how you are thinking about the target population? Would this initially focus on pediatric patient, age 10 and above? Or could we also think about a broader approach over time, potentially extending into adult populations?

Thanks, Justine. Alberto, do you want to take that question?

Yes, of course. I start from the last part. Certainly, we will need at 1 point to do as a line extension potentially to look at adults assuming, we will be successful in the children pediatric population. For looking at the population, I cannot say much. But indeed, we -- one of the things that we are trying to target is really to identify a specific neurodevelopment disorder, not in general disorders, for which we have specific scale, which are agreed by the health authorities. So I would certainly say that at the end of the analysis that we are doing, further analysis that we are doing on the children that we have between ASD and ADHD, 2 neurodevelopment disorder that we have in our study, we will be able to choose 1 and then get -- as Jean-Paul said, not a simple study, never simple study in this disease. But certainly, not in insomnia, but looking at the symptoms and therefore, using questioners. Did I answer your question or...

Yes, yes, you did.

Thanks, Justine. Are there any further questions, Nadia?

There are no further questions for today. I would now like to hand the conference over to the management team for any closing remarks.

Thank you, Nadia. If there are no further questions, we will conclude today's call. Thank you all for joining us today to look at these exciting results. Nadia, please close the lines.

This concludes today's conference call. Thank you for participating. You may now all disconnect. Have a nice day.

Good day, and thank you for standing by. Welcome to the Idorsia Full Year 2025 Financial Results Conference Call and Webcast. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to our first speaker today, Srishti Gupta, CEO. Please go ahead.

Thank you, Nadia. Good afternoon and good morning, everyone, and welcome to our webcast to discuss the financial results of 2025. My name is Srishti Gupta, I'm the CEO of Idorsia, and I'll start the call today with an overview of the operational progress we made in 2025 and the exciting plans we have for 2026. I'll then hand it over to Arno Groenewoud, our CFO, to walk you through the company's financial position. We'll then take your questions.

Next slide, please. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties and other factors. These may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements.

Next slide, please. We entered 2025 facing significant financial pressure, but we leave the year stronger and more focused. 2025 was a year of stabilization and preparation. We reinforced our balance sheet, delivered disciplined commercial execution and positioned our pipeline for decisive milestones ahead. Most importantly, we continued advancing medicines that address meaningful unmet needs for patients.

Our Idorsia-led QUVIVIQ sales for 2025 have more than doubled compared to 2024, rising from CHF 60 million to CHF 134 million, just above our target, which we upgraded in May last year. This performance was a result of strong commercial traction and growing demand for QUVIVIQ in Europe and Canada, the stabilization and optimized model in the U.S. I will share more on this later.

Our non-GAAP operating results have improved from a loss of CHF 308 million to a loss of CHF 100 million. Key to this operational recovery has been our commercial strength paired with cost control. Arno will share more on our financial performance later.

Next slide, please. Idorsia represents a rare combination of valuable assets. We are a commercial stage pharma company with 2 products that have blockbuster potential. We also have a rich pipeline of first or best-in-class medicines.

We have a clear path to making QUVIVIQ the standard of care in insomnia. In parallel, we are actively engaging in partnership discussions to maximize the value of TRYVIO/JERAYGO and change the treatment landscape of uncontrolled hypertension. We also have plans to advance our innovative pipeline, leading where we can and partnering where we should.

Next slide, please. Let's start with QUVIVIQ. As you know, QUVIVIQ is a best-in-class dual orexin receptor antagonist. It works by suppressing an overactive wake signal rather than sedation as some older drugs tend to do. As a result of this mechanism and the best-in-class pharmacokinetic properties, we can confidently say that only QUVIVIQ offers restorative sleep and revitalized days.

Before we talk about the commercial performance of QUVIVIQ, it's important to ground ourselves in the patient experience of insomnia. Insomnia is not just the loss of a night's rest and it does not end when the night is over. It infects the entire next day.

Patients describe difficulty focusing, feeling emotionally depleted and struggling to keep up with work and family responsibilities. What they value most is a treatment that helps restore their ability to function during the day. That next-day benefit is what matters to patients and it's central to how we think about addressing this condition.

Next slide, please. We continue to expect sales growth of QUVIVIQ in 2026 as we guide to sales of around CHF 200 million, but this is just a step on our path to changing the treatment landscape and becoming a global blockbuster. We have a clear plan to achieve this. First, market expansion in Europe and Canada; second, unlock the true value of QUVIVIQ in the U.S.; and third, continue to build a global brand. Let's look at the progress we are making on this and what's ahead.

Next slide, please. In Europe, QUVIVIQ is the only pharmacological treatment for long-term management of insomnia disorder. Our 3-pronged approach to market expansion in Europe and Canada is proving very successful. First, we secure public reimbursement. Second, we invest in focused promotional efforts targeting psychiatrists, neurologists and sleep specialists. Finally, we expand into primary care with co-promotion partnerships.

Starting 2025, we had secured reimbursements in France, Germany, the U.K. and the private insurance markets in Switzerland and Canada. We continue to focus on reimbursement. And during the year, we obtained public reimbursement in Austria, successfully negotiated premium reimbursed price in Germany, entered price negotiations in Quebec, while submitting in Finland, and continuing our discussions in Spain.

This continues to be our top priority for additional markets. And in 2026, we expect to secure public reimbursements in Spain, Finland and Quebec while preserving our price corridor, submit in the Republic of Ireland and continuing discussions in Sweden, Italy and the rest of Canada.

Our promotional efforts targeting psychiatrists, neurologists and sleep specialists are leading to strong positioning in retail and hospital settings. We've expanded into primary care with co-promotion partnerships with Menarini in France in October 2024 and Germany in April 2025. And in February 2026, we added the U.K. This is having an incredible effect on our reach, and we continue to look for partners who have established presence and relationships with GPs in other countries.

The result of these efforts has been an outstanding trajectory, particularly in France, but closely followed by Germany, the U.K. and Switzerland when considering the relative market sizes. And that trajectory can continue. Just to highlight a few markets, demand in the final quarter of 2025 increased by 25% in Germany, 38% in Canada and 45% in the U.K.

Next slide, please. In the U.S., in 2025, we executed a targeted digital marketing strategy with Syneos Health to establish stabilize sales and maintain our core patient base. Going forward, ensuring more patients have access to QUVIVIQ remains a priority. To achieve this, we are advancing 3 key initiatives.

First, descheduling the DORA class, recognizing the safety in the same way as it is recognized in all other countries. This would simplify prescribing, facilitate access, expand the prescriber base and improve the patient experience, especially with regards to refills.

Second, we will conduct a streamlined label-enhancing clinical study agreed with the FDA to have QUVIVIQ's benefits on daytime functioning recognized in the U.S. label, again, in the same way as it is recognized in all other countries. This would reinforce our differentiated profile with physicians, patients and payers.

Third, we will be launching a direct-to-patient digital distribution model aligned with the evolving U.S. market and to increase access.

Next slide, please. In 2025, we continue to expand QUVIVIQ's global reach and change the standard of care for insomnia with new approvals, launches and strategic commercial partnerships. Several license agreements help cover markets shown here in green.

QUVIVIQ is available in Japan through our partner, Nxera, and they recently saw positive Phase 3 results in South Korea. Our partner, Simcere, has had a very strong uptake in China within the private setting with 300,000 to 400,000 patients treated within the first 6 months.

In June, we signed a licensing and supply agreement with CTS in Israel and more recently in 2026 with EMS in Latin America. In Brazil, the regulatory dossier has been submitted to ANVISA, marking an important step forward towards market entry in that region.

In red, you can see the next wave of planned distribution agreements focused on Central and Eastern Europe as well as the Middle East and North Africa. These partnerships are part of our strategy to broaden geographic reach efficiently. We expect to make further progress through mid-2026, and we'll keep you updated as these agreements are finalized.

Next slide, please. In 2025, we completed the recruitment into our pediatric study of daridorexant, enrolling children aged 10 to 18 with data expected in early Q2 2026. This will be an exciting readout that can pave the way for the first therapeutic option for children suffering from insomnia.

Pediatric insomnia is a major unmet need with an estimated 12 million children in the U.S. affected and no FDA-approved therapies available. Insomnia is more prevalent in children with neurodevelopmental disorders like autism spectrum disorders and attention deficit hyperactivity disorder, and our study includes these patients.

Daridorexant is the only DORA in pediatric development and, as the new standard of care, could revolutionize the treatment paradigm. We are particularly excited to share the results in the coming weeks and discuss the path forward with regulators.

Next slide, please. Our second approved product is aprocitentan, commercially available under the trade name TRYVIO in the U.S. and JERAYGO in EU. We secured regulatory approvals in the U.K., Switzerland and Canada during 2025. It is the only -- the first and only endothelin receptor antagonist approved for the systemic hypertension market. We are actively engaged in partnership discussions, evaluating global and regional deals. Our objective is to expand access for patients while creating value for all stakeholders.

Next slide, please. TRYVIO/JERAYGO is uniquely placed in the treatment landscape for difficult to control or resistant hypertension. Its efficacy and safety profile differentiates it to existing therapies and any of those in development. Our registration trial, PRECISION, remains the only hypertension study to enroll true resistant hypertensive patients, all on 3, 4 or more drugs when entering the study. Notably, there was no exclusion based on any antihypertensive drug class.

It also had the broadest inclusion criteria, including patients with eGFRs as low as 15. Aprocitentan delivered a double-digit blood pressure reduction of 15.4 millimeters of mercury in just 4 weeks, on top of a standardized triple therapy administered as a fixed-dose combination pill.

Aprocitentan has an excellent safety profile with low discontinuation rates observed over 40 weeks, no drug-drug interactions and no increased risk of hyperkalemia, hypotension or a decline in eGFR.

The FDA approval provided a broad U.S. label that indicates TRYVIO is suitable for use in all patients who are not adequately controlled on other therapies with the cardiovascular outcome benefit cited within the indication statement.

TRYVIO benefited from several important derisking milestones in 2025. In March, the FDA removed the REMS requirement, simplifying prescribing and distribution. Then in August, aprocitentan was incorporated into the updated comprehensive hypertension guidelines issued jointly by the American College of Cardiology and the American Heart Association, which was an important step in reinforcing its role in clinical practice.

Our recently published CKD subgroup data shows strong blood pressure lowering plus significant reductions in proteinuria, supporting TRYVIO as a compelling and differentiated option for these patients. Market access work for JERAYGO is also underway in Europe to support our partnering efforts.

Next slide, please. TRYVIO is currently being prescribed at more than 25 of the top hypertension centers as part of our focused prelaunch activities to generate on-market experience. In the clinical setting, we see consistent double-digit blood pressure lowering across subgroups, including CKD stages 3 to 4 with excellent safety and tolerability. We see prescriptions coming from key specialties, including nephrology and cardiology.

Early on-market experience is translating into increasing new patient starts and improving refill rates, reflecting growing physician confidence in the therapy. Prescribers report meaningful and reliable blood pressure control and comfort using TRYVIO across diverse comorbid patient types. TRYVIO's early real-world experience confirms and reinforces the pivotal trial data from PRECISION.

Next slide, please. Our U.S. label allows us to target patients with uncontrolled hypertension despite treatment on 2 or more therapies. Within this broad patient population, there are clear and identifiable patient subgroups that would be the natural initial choice for prescribers. These include patients who remain uncontrolled despite treatment with 3 or more therapies, truly resistant hypertension by definition. This is a group with significant unmet need and high clinical urgency.

Second, patients with uncontrolled hypertension and comorbidities where endothelin is known to play a role, such as diabetes and obesity. Third, there is a clear need among patients with uncontrolled hypertension and chronic kidney disease, including those with eGFR down to 15. In this setting, TRYVIO offers a differentiated option without the hyperkalemia risk or eGFR decline that often limits other therapies.

Importantly, our on-market experience shows strong uptake across these same patient segments. Notably, given the significant unmet need and clear medical value in these patient populations, the prior authorization process has been very smooth.

Next slide, please. Let's turn now to our pipeline. 2025 was a year of meaningful progress, laying the foundations for long-term growth. We are making deliberate focused investments to accelerate our most value-creating assets, supported by a leaner and more streamlined R&D organization. We have advanced our first-in-class immunology portfolio of 3 chemokine receptor antagonists.

The study for our CCR6 receptor antagonist is already enrolling in psoriasis with broad potential in T helper 17 driven autoimmune disorders. A study to show anti-inflammatory and remyelinating properties of our CXCR7 receptor antagonist is in progress and progressive multiple sclerosis will start shortly.

And a study for our CXCR3 receptor antagonist as an oral precision treatment for vitiligo will begin later in the year. Each will be a proof of concept in a specific indication under investigation as well as a proof of mechanism for a range of related disorders.

Next slide, please. We recently announced the exciting news that we have established a clear route to registration for lucerastat in Fabry disease. Fabry disease is a serious and progressive condition affecting around 16,000 people today, a number expected to rise to 21,000 by 2034. There is a high need for treatments capable of addressing disease biology across the full Fabry population as existing therapies are partially effective, have cumbersome intravenous administration or are limited to specific mutation types.

Lucerastat's mutation-independent mechanism, oral delivery and long-term data make it uniquely differentiated option in a market expected to reach USD 4 billion. The body of evidence we have generated to-date shows that long-term treatment with lucerastat consistently reduces the glycosphingolipids substrates that accumulate in Fabry disease.

We also observed a slower decline in kidney function compared with patients' prior historical trajectories. Importantly, kidney biopsy data from patients receiving long-term treatment demonstrate low to no levels of characteristic lysosomal deposits per our related data recently published at WORLD Symposium 2026.

Next slide, please. Following constructive interactions with regulatory authorities, we now have a clearly defined clinical program for lucerastat. This program builds on the substantial body of data already generated and outlines the agreed path towards future NDA in the U.S. and in line with feedback from the European Medicines Agency.

The agreed development plan includes a pivotal baseline controlled biopsy study supported by a second study designed to demonstrate that an oral therapy has the potential to deliver clinical benefits comparable to enzyme replacement therapy, which is complex and burdensome for patients.

This developmental program is structured to reinforce lucerastat's potential as the first oral monotherapy suitable for all Fabry patients regardless of mutation type. If successful, the data are expected to support regulatory submissions as early as 2029.

With that, I will hand it over to Arno to take you through the financial results and our guidance for 2026.

Next slide, please.

Thank you, Srishti. Good afternoon and good morning to everyone on the call. In my first slide, you can really see the impact of our increased QUVIVIQ sales and contract revenue, together with our cost-saving measures, resulting in a significantly improved operating result.

Net revenue of CHF 214 million includes CHF 134 million from QUVIVIQ product sales, excluding partner sales, a significant increase compared to the CHF 61 million of sales in 2024. The main driver of the sales increase is the EUCAN region, where sales increased from CHF 32 million to CHF 108 million.

The sales in the U.S. remained flat despite a significant reduction in sales and marketing costs. As mentioned by Srishti, the aim is to maintain our U.S. prescriber and patient base in a cost-efficient manner to bridge to a potential descheduling.

Non-GAAP contract revenue of CHF 72 million includes the USD 35 million exclusivity fee from the undisclosed partner for aprocitentan that was received in Q4 '24, but recognized in Q1 '25 after the exclusivity period ended without resulting in a deal.

As a reminder, the undisclosed partner was not able to close the deal for reasons absolutely unrelated to aprocitentan. In addition, we received a CHF 40 million signing and approval milestone from Simcere related to the out-licensing of QUVIVIQ in China.

The cost rationalization efforts initiated in '24 and '25 further improved our operational cost base with savings of more than CHF 80 million compared to 2024. As a result, the non-GAAP operating results improved from a loss of CHF 308 million in 2024 to a loss of CHF 100 million in 2025.

Based on successful negotiations with Viatris in Q1 '25, Idorsia's cost-sharing commitments were reduced by USD 100 million against a reduction of potential future regulatory milestones. This resulted in a gain of CHF 90 million. Other non-GAAP to GAAP differences mainly include depreciation and amortization and stock-based compensation.

This resulted in a U.S. GAAP EBIT loss of CHF 33 million. The U.S. GAAP net loss of CHF 112 million also includes the financial expenses of CHF 72 million, which also includes a CHF 61 million noncash expense related to the convertible bond restructuring and the new money facility. And we had an income tax expense of CHF 6 million.

Next slide, please. In addition to outstanding -- to an outstanding operational performance in 2025, we were also able to successfully strengthen our financial position and access to liquidity. As you know, we started the year with CHF 106 million in cash. Operational cash inflows included CHF 142 million from QUVIVIQ product sales, including sales to partners, and operational cash outflows included CHF 215 million of SG&A and CHF 93 million of R&D costs. The CHF 11 million other cash outflows mainly included working capital movements.

Further, as announced in May '25, we secured a CHF 150 million funding facility from our bondholders. And in June '25, we drew the first tranche of CHF 70 million. We also raised CHF 68 million net of cost through an equity raise in October '25 by way of an accelerated book building process as well as the sale of some of our treasury shares to bondholders.

We were very happy with the oversubscribed demand from the top-tier institutional investors that participated in the book building process. This resulted in a liquidity of CHF 89 million at the end of the year. And in addition to that, we still have access to a further CHF 80 million from the new money facility, which totals CHF 169 million liquidity available to Idorsia.

All in all, I think we can conclude that we finished the year with a strong liquidity that puts us in a good position to fund our activities going forward and leading to next inflection points.

Next slide, please. Here, we come to the comparison against the guidance. We are proud of our strong performance against an ambitious guidance target, which was significantly upgraded in May 2025. Our QUVIVIQ sales of CHF 134 million exceeded the guided sales of CHF 130 million due to an excellent execution of our commercial strategy, as Srishti already alluded to.

The company also delivered on the announced reset of the cost base. And as a result, the operating expenses, net of other income, were in line with the guidance that we provided in May '25.

The U.S. GAAP operating loss of -- or U.S. GAAP loss of CHF 33 million is lower than the guidance, mainly due to one-off lower stock-based compensation costs. Equally important compared to achieving the financial guidance for 2025 is that we've built the structures to transition this momentum into the future.

Next slide, please. We continue to guide on Idorsia net sales, excluding sales to partners because this is the performance that we can actively steer and have control over. We expect a continuous QUVIVIQ sales growth and with sales of CHF 200 million, we will have a positive commercial contribution for the first time.

Our 2026 OpEx, including cost of goods sold, will be flat compared to 2025, a little bit higher than might be anticipated in the market, but purposefully so, focused on creating shareholder value and within strategic guardrails. Our 2026 OpEx is fully consistent with a disciplined plan that supports the next wave of growth drivers. These expenditures are targeted, program-specific and clearly tied to our medium-term value creation plans, such as lucerastat program and the proof-of-concept studies with our immunology portfolio.

In a nutshell, sales are going up, OpEx remains flat and overall losses are going down, reflecting the improved underlying business performance and the embedded operational leverage within our business model.

And with that, I hand over to Srishti.

Next slide, please. Thank you, Arno. 2026 is shaping up to be a catalyst-rich year across commercial execution, strategic partnering and important scientific readouts. We are particularly looking forward to sharing the pediatric insomnia data in early Q2, along with several additional milestones throughout the year that we believe have the potential to meaningfully advance our portfolio and create value for shareholders.

Next slide. With 2 approved products with significant commercial potential and a pipeline of first and best-in-class compounds, Idorsia is positioned to create meaningful value. I am proud of the team's performance in 2025. We delivered on upgraded ambitious guidance, accelerated QUVIVIQ's commercial trajectory and continued building the foundation for long-term growth.

TRYVIO/JERAYGO represents the fourth endothelin receptor antagonist brought to approval from our pipeline, underscoring our deep expertise in this pathway and its potential in an area of high unmet need. We continue to advance other assets with discipline and focus. And as we look to 2026, we are committed to executing against even more ambitious objectives with a clear focus on delivering sustainable growth and long-term value.

With that, Nadia, please open the line for questions.

[Operator Instructions] And now we're going to take our first question. And it comes from the line of Raghuram Selvaraju from H.C. Wainwright & Co.

Firstly, I was wondering if you could elaborate a little bit further on the digital distribution model for QUVIVIQ. And specifically, a, how you anticipate this to have an impact on the forward sales trajectory; b, how it might improve your operating efficiency going forward; and c, how it could conceivably be leveraged for the use of launching additional products in the future or if it's going to be very specific to the needs of QUVIVIQ as a product franchise and wouldn't be applicable necessarily to other potential products that you bring to market in the future?

And then secondly, I was wondering if you could provide us with kind of what you see as the ideal time frame within which you would want to have a TRYVIO/JERAYGO partnership in the United States as well as regarding guidance, just some clarificatory points. Are you still confident in the previous 2027 top line guidance? Or how has that changed? And are you including in that forward assessment any potential contribution from TRYVIO/JERAYGO? Or is that going to be entirely driven by organic growth in the internal products over which you maintain commercial control?

Thank you, Ram. So the first question, area, we can tackle first on the distribution model that we're thinking about for the U.S. for QUVIVIQ. Is that the first question, area?

Yes.

And so we have -- yes, we're thinking a little bit about -- I mean, what we've learned from the weight loss space is that when there's a high degree of self-diagnosis, the ability to then find a provider and find -- be able to go into online to broaden access and broaden the availability to patients that that can have a huge unlock for certain therapeutic areas.

And we very much believe that sleep could be the next therapeutic area that could benefit from this type of model. So we've been exploring right now in the U.S. how we could do a direct-to-patient distribution model for QUVIVIQ. We've heard this is a friction right now in terms of both on the prescriber side as well as on the distribution side with pharmacies that they're not always stocking because of the DEA oversight. And so what we've understood is that some of these models for distribution can consolidate the regulations and the oversight, both on the telehealth providers as well as for the distribution. And so that's what we're exploring right now to start as a pilot in 2026.

So we definitely anticipate that this could -- in addition to our current model, be on top of that, we would anticipate that as we can get this up and running, it would have some forward momentum on our sales for QUVIVIQ. And then we would also expect that given its efficiency, we could, at some point, it would have impact as having a lower OpEx.

DTP models are common now, are getting more and more common in the United States. And so we would anticipate that if we were to make other products like TRYVIO available through that model, it might actually have an impact. But right now, the current focus really is QUVIVIQ, especially because we have more experience with QUVIVIQ and understand the points of friction that were there for patients and prescribers.

So then moving on to your second question area of TRYVIO and the ideal time frame for a partnership in the U.S. I mean with the approval and the availability of TRYVIO in the U.S., obviously our focus is to make sure that this is available to patients as soon as possible. We would actually love to scale. We know that patients are benefiting already from our focused efforts to introduce this in the top hypertension centers.

Prescribers are very eager to make sure it's available to patients. So we would absolutely love to be able to build on our very, very focused prelaunch work and scale that through partnership. And so that is top priority for the company right now is to be able to find a partner and move that forward as soon as possible.

And our efforts to do all the work that we've done on distribution with Walgreens Specialty, our work with the hypertension centers, our work on the guidelines and making sure that we're continuously present at conferences and hosting ad boards and working with KOLs is really to make this as turnkey as possible for a potential partner. So we would love to make sure that as they -- as we find that partner in the U.S. that they are able to make TRYVIO available to more and more patients.

In terms of your questions on guidance, I'll start with that, and then I'll hand it over to Arno. I think right now, the company is really focused on guiding on a one-year timeline. I think with the catalytic events and sort of the unknowns with things like descheduling, the partnership timeline, we -- it's not meaningful to guide beyond a year. And so our 2027 with outlook that we provided in May 2025, at the time it was the best available information we had. But of course, as we move forward, we are seeing more data. We see potentially we could see the descheduling, we could get more information on partnership. And so our forward-looking guidance could change in the next year. I think 2026 is actually quite a shaping year for us.

But with that, I'll hand it over to Arno to see if he has anything to add.

Yes. Maybe also to take it a bit broader because, I mean, the outlook that we gave in May 2025 was in the context of the whole financial restructuring. And I think after that, I think with the 2025 performance and the guidance for '26 and in particular, the growth of QUVIVIQ sales, we are really making clear steps to profitability and cash flow breakeven.

The 2025 sales were in line with our guidance. And our guidance for '26 is also in line with what we said in May 2025. But like Srishti said, I mean, going forward, we will limit our guidance to the current year as there are many variables and inflection points in '26 and onwards in commercial, in partnerships and also with our pipeline. And considering these moving parts, I think giving guidance beyond 2026 would not be meaningful for the market. And we would like to stay credible and transparent with guiding on numbers where we have a solid visibility.

Yes, of course. Now we are going to take the next question. And the question comes from the line of Joris Zimmermann from Octavian.

This is Joris Zimmermann from Octavian speaking. Two, if I may. First, on the QUVIVIQ pediatric data that you expect later this year in I think Q2, what is the immediate impact that you expect and kind of the next steps that would follow those data? And then also a bit from a longer term perspective, what's your strategy here? Will you pursue an updated label? Does it have -- does it come with a pediatric extension as well? So that would be on QUVIVIQ.

And then the second question on your cash and cash reach. With the current cash of around CHF 89 million and the CHF 80 million remaining from the new money facility, how would you assess your funding situation? Kind of what is the estimated cash reach? And does that include all the costs to cover the -- kind of to drive your pipeline assets and to reach all the key inflection points that you outlined in the presentation?

Joris, thank you for joining, and thank you for the questions. I'll take the first one and hand the second one over to Arno. On the pediatric QUVIVIQ daridorexant study that is -- we're expecting in Q2 2026, it's a dose-finding study. So we tested in 3 doses and we'll do a dose response curve. And so what we're expecting hopefully to see is both positive results with daridorexant in insomnia in the pediatric population as well as to get some data on the dose.

The next step would then be to take that information to the regulators and agree on a pathway forward, both with the U.S. as the FDA as well as the EMA. So we would have to run a Phase 3 program. We're expecting to be running a Phase 3 program, but we would like to shape that program based on the findings of the Phase 2. So that's where we are on the data.

I mean we're very excited, though, because there is no FDA-approved therapy for insomnia in this pediatric population. And there are no other doors with the safety profile that does non-sedative to work on the wake signal in this population. And as we know from the data that we have in the adult populations that we use all around the world, the daytime functioning could have a huge impact for pediatric patients as well. So we're very curious to see how the Phase 2 results pan out, and we're very curious to be able to shape a Phase 3 program that is able to do that later.

The other part of it for me that's very exciting is that there's the huge safety halo that comes from having a product that's effective in the pediatric population. And especially in the United States where we've had the burden of being a Schedule IV product, we would love to be able to have the safety halo that comes from showing use in the children with insomnia.

With that, I'll hand it over to Arno.

Yes. Thanks, Joris, for your question about the cash and the cash reach. I think we're very fortunate that we have a very strong liquidity at the end of the year with CHF 169 million. We clearly have sufficient cash to bring us to the next inflection points. And as already mentioned by Srishti with the previous question, I mean there are many variables and inflection points to come. So that will also clearly have an impact on our cash need going forward. But for now, I'm pretty happy with the cash runway that we have and that we're able to reach the inflection points based on which we can take additional decisions on whether to further invest or not.

Now we are going to take our next question. And the next question comes from the line of Niall Alexander from Deutsche Bank.

Hi, it's Niall Alexander from Deutsche Bank. So I guess maybe just moving to the pipeline, just on your CXCR7 antagonist in MS, I understand it's just a proof of concept right now. But it would be helpful to understand how you feel this mechanism could potentially be differentiating, and especially so to the likes of the CD20s right now or even the BTKs in the space. Just trying to understand what your hypothesis or views are on the mechanism. And then the same applies to the CCR6 and CCL20 in psoriasis. Just wondering how the mechanism there can potentially be different from the likes of IL-17s and 23s in this space.

Thank you, Niall, for the questions. Maybe I'll start with CCR6 first because that's the one that's enrolling right now. So it's a first-in-class oral small molecule, and it's selective for the CCL20-driven recruitment of the pathogenic CCR6 expressing immune cells. So we -- first thing, I think, is the potential for an oral therapy that delivers a biologic-like efficacy, and that's very compelling. We've designed the trial that evaluates the speed and the magnitude of the response as well as the dose performance and safety in the T helper 17 driven psoriasis in the PASI. And the reason we went with that test as well as with this -- with psoriasis is because that mechanism is the most clean. I think we don't see sort of off-target in that area. So we were really hoping that we could get a clean response on the PASI. So a positive outcome in this proof of concept would confirm that in the mechanistic validation and the expansion to other associated indications. And so that's kind of what we're thinking about for CCR6.

In terms of CXCR7 and the kind of the unique or the differentiating is that we have this oral, again, that is both potentially anti-inflammatory as well as remyelinating. And the brain penetrating potential is quite strong, which would have an impact in the -- to be able to transform the treatment paradigm in MS. And so the proof of concept is primarily the progression and so of the multiple sclerosis. And so what we're trying to see is if we can -- through the -- its imaging -- yes, with via imaging, we could see a slowing of the demyelination. And so that's kind of our -- the proof of concept that we've designed for the CXCR7.

Now we're going to take our next question. And the question comes from the line of Sushila Hernandez from Van Lanschot Kempen.

This is [ Sandrine ] on for Sushila. We have 2. First, could you provide more of an update on the QUVIVIQ descheduling process? Like how likely is it that it will happen this year? And second, on the Fabry disease, now that you've reached alignment with the FDA, what are the next steps? Like when will you start the kidney and the renal studies?

Thank you, Sandrine, thank you for joining. So on the first question on descheduling, we expect the next major update to be the initiation of the public comment period from the DEA. And so that's the next time we think we'll have public information available on the descheduling process.

In terms of where we are, I mean, we've now seen that -- we have probably around 13 million patients ex U.S. that have been on ADAURA across the globe between Japan, China and Europe and a couple of million patients in the U.S. And we consistently know that QUVIVIQ is valued for its safety. We don't see any meaningful signals of abuse dependence or withdrawal. And so part of our update to the FDA has been to share this kind of comprehensive ex-U.S. data.

This is on top of the Citizens Petition from '23 and a recent update that we did to the FAERS analysis. So the FAERS is the FDA's own adverse event reporting system database and where we -- again, we went back to the database and we did an updated analysis and we demonstrate that the DORA class has significantly reporting odds for adverse events related to drug abuse compared to the Z drugs and other nonscheduled drugs such as trazodone, which are used in the U.S. off-label. So we're kind of combining those things in our mind and hoping that the FDA's recommendation that moves forward is to be descheduled, but we'll only know when the DEA opens it for public comment.

That being said, I think it's important to know that we're not waiting for the descheduling to unlock the value of QUVIVIQ in the U.S. The daytime functioning in the label, the label-enhancing study as well as the work with the direct-to-patient, we're setting up those -- we're setting up the model on direct-to-patient to be able to accommodate for the current schedule as well as then expand based on any descheduling that happens.

So we are really focused on making sure that even in its current form that we can increase access for patients and they can have the benefit. And then, of course, all of those things in total, as we get more and more patients on QUVIVIQ, we can update the FDA with the safety profile and the lack of abuse signals. So that's the question, I think, probably on descheduling, but we'll only know when it goes from the DEA into public comment.

On Fabry, we're expecting to initiate the pivotal study for the biopsy in this year. And so that's the pivotal. That's the 16 patients I showed it earlier. It's baseline controlled. We're expecting to take patients that are treatment naive or pseudo-naive, and it's 18 months of treatment, and we're expecting that it's in our budget to be starting that study this year. Soon thereafter, we'll do the second study, which is to show the switch from ERT. So we'll take patients that have been on ERT therapy for a year or more, and we'll do the switch study. And so with the idea that we'd like to submit in 2029. Did I answer?

[Operator Instructions] And the question comes from the line of Myles Minter from...

Congrats on the progress. A couple on lucerastat. Just wondering if you can comment on kind of the powering assumptions for that 74-patient renal function study that you're doing against ERT in Fabry. And then I noticed at the WORLD Symposium, you seem to see a greater efficacy signal in patients with pretty severe declines in eGFR but at baseline and also antidrug antibody positive patients on the ERT side. So I'm just wondering whether you're going to stratify the readout of that trial in any way based on those factors?

And the final one is just in terms of the number of patients that remain in the open-label extension there. I think it was 47% of the original amount that crossed over. Can you just provide any sort of major reasons as to why there was discontinuations there? That would be very helpful.

Myles, thanks for joining, and thanks for the questions. I think your first question was on the power of the second study. So we were not requested by the FDA to power the eGFR study. And so that's -- so we were working under the assumption that we don't have to have statistical significance. So we designed that study with that idea.

In terms of the WORLD Symposium, the decline in the eGFR and the antibody and the stratification, I think we'll have to see where we are in terms of the eGFR study and the enrollment on how we might want to stratify that study. But right now, as we're looking for a broad monotherapy label for all adult patients with Fabry, we're not looking to kind of have a specific use in those patients with ADA. We are trying to get the label to be as broad as possible. We would like to make sure that our study design is consistent with that.

And then finally, on the open-label extension for MODIFY, that was 43 months, which was, I mean, I think, 6 years, right? Like we're in total with the 6-month MODIFY trial, that's 6 years. I mean 50% is actually a really good retention rate after 6 years. I don't know if there's anything I'm doing right now that's the same as I was doing 6 years ago. So I think that retention rate actually seems pretty good for this type of study for chronic -- for a daily oral and with for chronic condition.

And the question comes from the line of Joris Zimmermann from Octavian.

One more question from my end on the aprocitentan partnering, if I may. I was just wondering, looking at like the data is there, the data is good. The first market feedback, to my understanding, is also very positive. And now you have the whole REMS requirements omitted and you're even in the guidelines. So I was wondering what is it that is kind of -- why do the aprocitentan partnering discussions still go on? Can you maybe comment on that? So is it more on the finding the right partner in the U.S. and Europe probably? Or is it more on the deal terms? What's kind of the main discussion topic you're currently having here?

Thank you, Joris for the question. The second -- the third question, actually. So I mean, there's a lot of the positives, right? We have the data, we have the market feedback, the REMS, we have the differentiation, especially for those patients that have an eGFR down to 15 where there are no other options. And we've been in the process of looking for a partner for a while, I mean, especially even to the time when J&J decided to not pursue work in cardiovascular anymore, and we took the rights back for apro so that we could bring it forward because we have such conviction in the endothelin receptor antagonist space and its ability to be used in systemic hypertension.

Now after the approval process, I think we have gotten into a point, we're having a commercial asset that has not had the ability to be resourced for a launch. That's a new mechanism of action that is -- needs to be introduced in a pretty complex health care system right now with incredible cost pressure. And with the commercial payer system that's highly under evolution with PBMs and it's like every other week, a pharma company is being hauled into the White House. I think it's really important for partners to be able to understand the commercial fit.

And so with a commercial stage asset, the commercial fit, I think, from the partner perspective is one of the things that needs to be worked out on both sides. Like, we need to see that they're able to resource that apro or TRYVIO gets to the patients and are willing to put the effort to make sure that TRYVIO can reach the most patients, but they also need to make sure that it fits with their programs given that it's commercial stage.

A lot of the -- sort of the sweet spot for most deals is kind of a little bit before Phase 3 or at this derisking stage where they can prepare the market. And so I think right now, we're just in a peculiar stage with TRYVIO, but we are actively engaged in a range of conversations. I think one last point to make is that the sort of complicated U.S. drug pricing system and its implications for internationally are also impacting. And so that's why I think we are exploring both global as well as regional partnership. We have 2 different labels, 2 different brands, 2 doses for TRYVIO/JERAYGO, and I think that gives us the flexibility to really pursue regional opportunities. And so that's also kind of evolved our focus on the partnership discussion.

Dear speakers, please be advised there are no further questions for today. And I would now like to hand the conference over to the management team for any closing remarks.

Well, thank you, everyone, for the time today. We will have our first quarter results on April 28. And together with some of the participation that we have in investor conferences on this side of the Atlantic as well as in the U.S., we hope to get the opportunity to speak to more of you in the near future. Thank you again for joining. And with that, we can close the lines.

This concludes today's conference call. Thank you for participating. You may now all disconnect. Have a nice day.

Hi. Good morning, everyone. My name is Farhan Khan, and I'm an associate with the Healthcare Investment Banking Group here at JPMorgan. It's my great pleasure today to be introducing Idorsia. Presenting today is Idorsia's CEO, Srishti Gupta. We also have key members of the leadership team, Arno Groenewoud, CFO; and Martine Clozel, who's the Co-Founder, Chief Scientific Officer and Head of Research, will be joining for the Q&A panel.

After the presentation, we'll have about 10 minutes for the Q&A. So please hold your questions until then. And with that, please join me in welcoming Srishti.

Hi, everyone. Thank you for joining us. I'm Dr. Srishti Gupta, the CEO of Idorsia, and it is a pleasure to be here. It's the first time I'm presenting at JPMorgan since becoming the CEO in July 2025. Prior to that, I was on the Board. I've been on the Board of Idorsia since May 2021. So today, I'll share the highlights of 2025 with you as well as our strategy going forward for 2026.

So for those of you who don't know us, we built on a proven foundation; the talent, The legacy, and the drug discovery engine of Actelion. And that's the reason we have conviction in our strategy. The teams, the core science and the capabilities that created so much value in the past are the same ones that will be creating value in the future.

We are executing a focused and balanced approach to our strategy, which is to commercialize our 2 assets as well as bring our pipeline forward in a disciplined and focused way. We're committed to creating meaningful value for our patients as well as for our shareholders. Before I begin, standard disclosures, we will be making forward-looking statements.

So Idorsia is unique because we have blockbuster potential products that are commercially approved as well as a pipeline of first and best-in-class drugs. So our 2 commercial products, QUVIVIQ, which is daridorexant. It's a dual orexin receptor antagonist is poised and ready to be changing the standard of care for insomnia.

We also have TRYVIO and JERAYGO which is the first approved innovation in hypertension in close to 3 decades. It is an endothelin receptor antagonist and is approved for the control of difficult-to-control hypertension. We have commercial footprint that extends North America and Europe and we have a global footprint through partnerships with companies like Nxera and Simcere.

On the pipeline side, our track record is proven. We have 3 drugs approved in the last 4 years. We have 3 additional Phase III assets and we're in the process of starting 3 proof-of-concept trials. Multiple assets in our pipeline have multibillion-dollar peak year sales potential. We're committed to creating meaningful value for our patients through changing the standard of care and how the diseases are treated.

So I'll start by talking about our 2 products, which are entering a value acceleration phase in the commercial side.

QUVIVIQ. Insomnia, it significantly impacts both productivity and public health. We think of insomnia as a 24-hour disease because it affects every aspect of life; how you function, how you stay safe and how you work. So we see a significant impact on the productivity side with over $400 billion of global annual GDP loss because of absenteeism, which is not showing up for work because of insomnia-related sleep disorders, presenteeism, showing up and not being productive at work and overall productivity loss.

More importantly, what we see on the public health side is an increased risk of accidents and permanent work-related disability as well as sleep and fatigue contributing to long-term sleep issues in health, like -- chronic issues like cardiovascular disease, stroke, dementia and psychiatric and other related disorders.

The biggest issue that is understated in the space of insomnia is the escalating public health crisis of mis and inappropriate benzodiazepine use. This is where Idorsia comes in. we have brought forward a best-in-class asset with QUVIVIQ. It is a dual orexin receptor antagonist, and it is designed for and here for both restorative sleep and revitalized days. QUVIVIQ is the only therapy to demonstrate an improvement in daytime functioning, with statistically significant and clinically relevant patient-reported outcome that was used in the registration trial. This was the patient reported outcome that had 14 questions across 3 domains: sleepiness, alertness and cognition as well as the mood.

And we saw a significant improvement in all 3 domains with 50-milligram use of daridorexant. While the daytime functioning is included in many labels around the world, it's not included in the U.S. label. So one of our focuses this year is to do a small and focused trial to include daridorexant in the label for the U.S. And why is this important? We need to do this because we have to show that insomnia is a 24-hour disease. We also need to prove that with physicians and patients that this is a distinction thing because there's no approved products that address the 24-hour aspect of the disease. No approved insomnia product has both nighttime as well as daytime functioning.

The problem right now is that insomnia is being treated inappropriately with benzodiazepines. And part of that is the U.S. health care system, which pushes people to products that are inappropriate for use because they're cheaper, not because they're better. And benzodiazepines happen to be cheaper. They don't have a daytime functioning claim. They don't address the daytime issues. So with a claim for daytime functioning, we would be able to show that we are differentiated and can preaccess things with payers. We've been able to build QUVIVIQ into a global brand based on the fact that we've been able to address the issue of insomnia -- we've been able to address the issue of insomnia as a daytime and nighttime disease in many countries around the world because we've been able to include it in the label.

So we have shown this in Europe where we have now changed the standard of care in many countries. And our partners in Japan, Nxera have been able to show this with daridorexant as QUVIVIQ in Japan, where insomnia treatments are close to 35% of the treatment for insomnia.

In China, we're seeing that over 100,000 patients in the first few months of launch have become our -- on QUVIVIQ and we're well on our way in Europe because we see that in Europe, we have countries like France and Germany, which we have more than 5% or 7% of patients on QUVIVIQ and in France, actually, what we're seeing is that the rise in QUVIVIQ use is coming with a drop in benzodiazepines.

We're well on looking to enter partnerships in LatAm, in MENA in Israel as well as Central Europe and other countries around the world. And the fact that we are able to create QUVIVIQ into a global brand is a proof point that it's a best-in-class asset that has the ability to change the insomnia market and we're able to kind of make sure that we're able to see that the blockbuster potential is there by relaunching in the U.S. So let's talk about that.

So we have the ability to change the advanced standard of care for insomnia. We've talked about Japan, where we have over 30% use. We have Europe, which is on the rise; China, which is on the rise. So what's going on in the U.S. So we have U.S. with the idea that there's currently dissatisfied patients. We have under 2% market is in the DORA class. We have high use of trazodone inappropriately, we have high use of benzodiazepines inappropriately and we have the opportunity to completely disrupt this market.

So what is our clear path to global blockbuster potential with daridorexant. We have seen in Europe that as a best-in-class asset, we are driving up sales. And we have a path forward with 3 ideas in the U.S. As you might know, in April 2023, we filed the Citizens Petition for the descheduling of the entire class of Merck and Eisai's product as well as our product. And so what we're trying to do is make sure that we're advancing the descheduling of this asset.

In addition, we're looking at new sales models. So we've seen with the GLP-1s and other products is the direct-to-patient models. And what we're excited to do is that we're taking the same model and trying to put it forward with other assets. I think the other big thing is the daytime functioning claim.

So without any other products in this space that have the ability to affect daytime functioning, we are able to bring something forward for insomnia, doesn't -- that includes something completely distinct. So the combination of what we see in Europe, the combination of the Europe, the U.S. relaunch and as well as expanding globally, we fully believe that QUVIVIQ has blockbuster potential. And with U.S. exclusivity at least to 2036, we definitely have the pathway to get there.

One thing that I think would be completely amiss not to talk a lot about is the fact that pediatric insomnia is a complete unmet need. And this is a staggering impact both on the patients as well as on the caregivers and families. There are no approved products for insomnia in pediatric patients in either U.S. or Canada. And the approved product in Europe is melatonin and with questionable efficacy. Children with neurodevelopmental disorders are even more severely impacted by insomnia. It's more chronic, it's more severe. It affects not only the children, but also affects their caregivers.

We've estimated the prevalence to be 10% to 30% in the U.S. alone, and that's about 12 million patients right off the back. QUVIVIQ or daridorexant, and Idorsia is the only company that's actually investing in a Phase II trial for pediatric investigation. So we have a Phase II dose finding study, which is coming up in March 2026. And our trial design has included patients with not only autism spectrum disorder as well, but also patients with attention deficit disorder.

The trial is fully recruited, and we're expecting results in Q2 2026. In addition, since we're the only one who has been pursuing this as part of our regulatory commitment, this would allow us to have some patent term extension. So I can't underestimate the impact that insomnia is having in the pediatric population. And we're excited to bring forth the first and best-in-class asset as the first mover advantage to be able to treat pediatric insomnia.

Let's move on to TRYVIO and JERAYGO, the first approved anti-hypertensive therapy targeting the endothelin system. These drugs are approved in the U.S., EU, U.K., Switzerland and recently Canada.

What is uncontrolled hypertension? It's a major public health problem. We estimate 1.4 billion people around the world are living with hypertension, with 30% to 50% of them being not well controlled. In the U.S. alone, we estimate 26 million patients not adequately controlled despite being on treatment with 2 or more medications. And when uncontrolled, we know that hypertension leads to a higher risk of stroke, kidney failure, heart failure or acute -- or heart attack.

Many patients will never be controlled unless you address the underlying pathology. And that pathology is often driven by endothelin. Endothelin-mediated hypertension needs to be addressed, and we have not well -- this is the first time we have a medication that will be targeting the endothelin system for systemic hypertension.

So let's talk about TRYVIO and why it's uniquely placed in this landscape. Idorsia invested in a trial called PRECISION and it took the hardest to treat patients who had truly resistant hypertension with the broadest inclusion criteria. The study was conducted in patients after they were screened on their background therapy, and then they were put on a run-in period. And both from the background therapy and after the run-in, they were checked for their hypertension, and they were still uncontrolled. So these are truly uncontrolled hypertension patients on 3 or more medications.

The inclusion criteria included a broad range of patients, including those with congestive heart failure, diabetes, obesity and chronic kidney disease. So we had patients in chronic kidney disease with an EGFR down to as low as 15. This is actually a very unique thing if you're following late-stage assets in the hypertension space because other assets have not been evaluated down to an EGFR down to 15. So all patients were on 3, 4 or 5 or more medications at the time of screening. So this was a very rigorous trial. Now what happened after that? The FDA actually gave us a label that was broader. So it's the first dual endothelin receptor antagonist approved for systemic hypertension for patients not adequately controlled on one or another medication.

So even though we did the trial in definitional resistant hypertension, the label that was received was much broader than that. And the mechanism of action because it's unique and sort of separate from the Renin-Angiotensin-Aldosterone System allows for the safe addition to those other therapies. We've been approved, and we've been on the market. And because of that, we actually can see what the emerging clinical differentiation is. We see excellent efficacy and safety across all patient subgroups including the double-digit blood pressure reduction that we saw during the trial and even better control over the longer period of time with no increased risk of hyperkalemia, no decline in EGFR or no orthostatic hypertension. Our approach to this has been to try to take our product to some of the highest -- some of the top hypertension centers in order to understand which patients and which physicians are using it.

But let's talk about the market opportunity. We see a path to $5 billion peak year sales because there's 26 million -- at least 26 million eligible patients for the product, with 8 to 13 million of those patients not well controlled. We see readily identifiable patient population, those with CKD stage III, IV, those with obesity, elderly, the African-American population. All of these groups are likely to have endothelin-mediated hypertension.

Using some reasonable penetration and adoption principles, we see about starting off with about 0.8 million to 1.6 million accessible patients. And then with the WAC price of $775 and the strong payer support that we're seeing with reasonable utilization management criteria, we can see a path to $5 billion peak year sales. With geographic expansion in the countries of approval as well as patent life extension beyond 2034, we also see the potential with expanded indications and further evidence generation.

We have excellent feedback from the market because we're already approved. So we are utilizing some of the top hypertension centers, including Colombia, Cedar Sinai, Stanford and Duke. We see the prescriber feedback confirms the PRECISION results, and we have good tolerability and safety across patient groups. Our approach has been to start with these top hypertension centers, establish a medical evidence base and then drive adoption with other physicians.

The types of physicians prescribing TRYVIO right now in the U.S. include cardiologists, nephrologists and internal medicine doctors. Here are some of the feedback that we see from physicians. 10 to 15 mmHg drop in blood pressure, well tolerated. First time patients have an option with -- for patients with an EGFR down to 15 not having to worry about hyperkalemia, not having to worry about monitoring blood test. Resistant hypertension has its complexities, and there was a patient with a clear need, which is now normalized with TRYVIO and again, confirming the double-digit blood pressure reduction, especially in context where patients were not tolerating other medications.

In terms of the patient populations, we actually see that we have both add-on use as well as switch. So add-on, we are seeing in truly with definitional resistant hypertension. We're also seeing in those patients that are not able to take other medications, so have an EGFR down to 15, to CKD type patients. So we see a large group of patients that these physicians are using that are add-on and then we see a large group that are switch. So these are switching from medications that are not well tolerated that include spironolactone, clonidine, hydralazine and switching because of the side effect profile, the dosing or the drug-drug interactions.

So let me move on to our pipeline, which is poised to deliver the next generation of breakthrough medications. We have 2 late-stage assets in partnership with Viatris which are driving some part of our long-term value creation. Selatogrel for acute MI and cenerimod for systemic lupus and potentially lupus nephritis. As you might have heard in the Viatris presentation, selatogrel is poised and ready to change the standard of care for acute MI. It's a potent fast-acting and regulated P2Y inhibitor, which is a self-administered therapy. So upon symptoms of an MI after having an MI, we have the ability to preserve heart muscle through the self-administration of this product.

It's a Phase III event-driven study that we're doing that we -- Viatris is leading on, and they're able to enroll about over 1,000 patients a month, which is an extraordinary sort of enrollment period, and they're working very hard to make sure that their current target of 14,000 patients is met and they're able to bring this medication forward. Cenerimod is a highly selective S1P1 receptor modulator. It's developed as a novel approach for lupus. Its enrollment is ongoing with the Phase III interim results expected at the -- for the first phase is expected at the end of this year.

These are 2 assets that we are working on with Viatris that they're on the lead on that we are not making any more capital investments on, but we have a royalty and milestone payment structure that would bring value to the company on our innovation. Beyond that, we have a Phase III asset called Lucerastat, which has the potential to define -- redefine the treatment of Fabry's disease. So Fabry is estimated at a $4 billion market and it's predicted to affect 21,000 patients in key markets, which include the U.S., European 5 and Japan. It's an oral alternative to intravenous ERT. And it's non -- it's mutation independent. So we started a trial about 7 years ago called MODIFY, actually more than longer ago, to call MODIFY. It had a several -- a primary endpoint of neuropathic pain, but also its secondary endpoint of EGFR slope as well as biomarkers for urinary and plasma Gb3 levels.

Unfortunately, we weren't successful in the primary endpoint, but we had very great data from the secondary endpoint and the exploratory end points. So we decided to do an open-label extension. We've published some of the results recently in Nature Communications on the interim open-label extension, and we're looking forward to presenting full results at the WORLDSymposium for Lysosomal Diseases in February.

Again, this is a market disruptor because we can have a full mutation independent oral alternative to Fabry's Disease. And with the program that we've run with the EGFR and the kidney biopsy substudy, we have the potential for demonstrating the renal protection or the renal preservation.

We also have a pipeline of first or best-in-class drugs outside of lucerastat. we have 3 chemokines. We've mentioned those in the past. We're very lucky to have Martine Clozel here today, one of our founders and our Chief Scientific Officer. And we're happy to go through some of the mechanisms and the trial designs on those. But at a very high level, we have CCR6, which is a receptor antagonist, which we're doing a proof of concept or proof of mechanism in psoriasis; CXCR7, which is a receptor antagonist that we're using with a proof of concept in progressive MS. This compound is potentially first-in-class and best-in-class in that it has the ability potentially to both be anti-inflammatory as well as remyelinating. And then we have CXCR3, which is a receptor antagonist for vitiligo, which we will be moving forward later this year.

So we're grateful to be in a financial position to drive our growth. And for those of you who have seen us in the past, this might not have been an obvious conclusion from last year's presentation. But we now have cash runway into 2028, we have liquidity or cash and near cash assets of about USD 258 million, and our revenue outlook is around $262 million from QUVIVIQ sales in 2026. We're looking forward to providing full year guidance in the end of February.

2026 is going to be a catalyst-rich year for us. We have several areas of focus, which include continuing the sales support for QUVIVIQ as well as new distribution models. We have the global expansion that we're continuing on QUVIVIQ. We have the USD scheduling possibility in the U.S. for QUVIVIQ for the class-wide descheduling. We're looking forward to moving forward on the partnership discussions on TRYVIO and JERAYGO. We'll expand our BD efforts across our pipeline to lead where we can and partner where we should. We'll advance the lucerastat registration as well as we'll initiate the daridorexant enabling study for the daytime functioning in the label.

On the R&D milestones, we're starting CXCR7 in Q1 later in this quarter. We will report on the results from the Lucerastat study. We have the pediatric readout for daridorexant in Q2 or early part of Q2. And we also have the midyear high dose results from the C diff vaccine on our synthetic glycan program as well as the initiation of CXCR3, and again, our partner, Viatris will be reporting on cenerimod later this year.

So again, here we are with Idorsia. It's a unique opportunity for value creation because of both the blockbuster potential products, which we're moving into a value acceleration phase as well as our best-in-class assets and which we are moving forward in a very disciplined way. I joined Idorsia as the CEO from the Board to bring value to our patients, to the people at Idorsia as well as to our shareholders. And with the management team, we're doing exactly that right now. And we are trying to be as balanced and focused as we can to create shareholder value as well as set the ground for innovation going forward. And really build off the revenue that we can get with our potentially blockbuster products that are on market today. Thank you very much for your time, and I look forward to answering your questions with the management team.

Thank you so much Srishti. I really appreciate that. Great presentation. So we'll kick off the Q&A session. So if you've got any questions, please feel free to raise your hand, and we'll bring a mic to you. And please hold your questions until the mic is brought.

[indiscernible] Morgan. A couple of questions from me. One was on TRYVIO just on the -- how you're thinking about the current proportion of patients that are coming from add-on versus switch therapy, just to put that into context a little bit more? And second question is on the ASIs. I think we'll see launches from one of them at least this year. So how are you thinking about the potential impact of that on the launch trajectory for TRYVIO.

Thank you for the question. I'll take the second question first. On the ASIs, actually very grateful that the ASIs are coming into the class because they'll help us define the therapeutic area of resistant hypertension. As we are a smaller company, and we originally had this asset with J&J, who no longer is in cardiovascular, it's been really hard for us sometimes to demonstrate that resistant hypertension is truly a disease state in a disease area. There's a lot of people out there who believe that this is a compliance question and not necessarily a distinctive disease.

And as we know, there's multiple drivers that are driving hypertension, especially when patients are on other therapies and the endothelin system has been widely underrecognized as one of those drivers for hypertension. So we're looking forward to having some of the education on the resistant or difficult to control or not well controlled hypertension being set by the larger companies who are coming into the space or other partners or other companies who are coming into the space.

And then we're looking forward to differentiating ourselves being the only drug approved right now for the endothelin component of hypertension. And then in terms of the other differentiations with the ASIs, I think it's a little bit of apples and oranges. If you look at the trial designs for those drugs, the inclusion criteria as well as what type of hypertension they were treating, they were not necessarily designed to treat truly resistant hypertension.

There was a component of resistant hypertension as well as uncontrolled hypertension in their trial designs and their inclusion criteria didn't go down beyond 45 eGFR, at least in their registration trials. So we have a truly distinct value proposition and that our inclusion criteria are much broader than that. And the mechanism of action is very different.

In terms of the patients on your first question on where we see the most patients or how we're seeing the distribution of patients between add-on and switch. I think it's a little bit early for us to tell. But I think that we do see the switch patients are definitely ones that -- where the distinct value proposition is very clear because they are not -- they're not tolerating or they're not effective on the blood pressure medications they're on. And given the high concerns around polypharmacy and drug-drug interactions, we see that physicians are very excited to kind of be able to move patients off of drugs where they're not effective into a drug that's immediately almost immediately recognized as effective in them.

And then in add-on, we do see it the most first and foremost, in definitional resistant hypertension because that's where the trial is the most unique. Martine, do you have anything to add on the patient population?

On the patient population, they will be cared to take for a prescription of ASI in combination with [ AHI ] would not be probably possible. Potassium will have to be taken into account the level of kidney function at baseline where we have a very broad possibility to use without a need to control for much except pregnancy perhaps. But otherwise, there is really no need for controlling before and during treatment. There is no need for blood control, no risk of hyperkalemia, no risk of degradation of kidney function, no hyponatremia.

We're looking forward to continuing real-world evidence, though, to be able to more clearly understand what the ratios are going to be between add-on and switch. Our guidelines are open to either one of them and the label is open right now because it's on one or another medication. But as we get more and more real-world evidence with use, we're looking forward to clarifying this and then really targeting our efforts.

People who have been trying, I think, 3 medications or more and have not been, despite compliance, able to improve the blood pressure are likely to have an endothelin dependent hypertension.

I've got a question for you. Just wanted to say, obviously, congratulations on the growth and momentum of QUVIVIQ. Could you better -- could you help us better understand what is kind of unique about the design of QUVIVIQ?

Martine, maybe I'll hand that one to you to some of the properties that make QUVIVIQ the best in class.

Yes. Thank you for the question. QUVIVIQ is a result of many, many years of work to optimize the molecule to have a duration of action which would not be beyond this duration desired of sleep. So the results of the compound is that we are improving by 1 hour per night sleep duration in patients who are either having difficulties to fall asleep or patients who have waking up in the second half of the night. And the effect of QUVIVIQ on both 30-minute improvement of time to fall asleep and 30 minutes shortening of the awakening.

What is quite incredible is that because of the pharmacokinetic and pharmacodynamic properties of the molecule, which was during the totality of 7 or 8 hours of night, the morning is not associated with any carryover somnolence effect. In the contrary, we have a dose-dependent improvement in alertness in the morning. And because of this profile, we have been able to think that we could potentially improve what is one of the biggest problems of insomnia and chronic insomnia in particular, which is daytime functioning impairment.

So we developed and validated the tool, which -- it sits with PRO, where the patients are asked on 14 questions every evening. And these questions have been optimized with insomnia patients, so they are highly relevant. And we have seen attached to the profile, improved quantity and improve quality of sleep. No carryover effect. We have been able to improve this daytime functioning rapidly, but increasingly even in efficacy over time, and that's completely unique.

Thank you, Martine. Okay. I've just got 1 more question and that I wanted to bring up. You mentioned the synthetic glycan vaccine platform. So can you just share a bit more details on that.

Martine, do you want to take one?

We had been at the time of Actelion been asked to try to create a [ newco ] with another approach to the research we have been doing on small molecule organic chemistry. And we decided after reviewing many, many different technologies to create this synthetic glycan chemistry-based vaccines. And we have started working with producing a few papers on different bacterial approaches. And we have decided to go first with Clostridium difficile, which is one of the very prevalent CDC cited priorities.

And this synthetic chemistry allows to make in the lab enough of millions of doses and to be able to have a highly reproducible vaccine. But in addition to that, it doesn't require growth of the culture of the bacteria. And Clostridium difficile, for example, is an anaerobic bacteria, which is impossible to grow.

This synthetic chemistry allows to mimic a glycan, which in the Clostridium difficile situation is a natural glycan. And we have, therefore, for the very first time ever, the possibility to target not the toxin, which are easy to target, but the bacteria and the [ spores ] . And we have obtained a proof of concept, which I think is very important for the C. diff development, but also as a proof of concept for our technology beyond the Clostridium difficile. So results are showing that we have immunogenicity only after 2 injections already in a dose-dependent fashion and that is antibodies which are developed are functional, recognize the bacteria and are functional.

Behind that, we have a portfolio of vaccines, Klebsiella pneumoniae. So we are really basically targeting the [ MRAs ], the bacteria which have high likelihood of multi-bacterial resistance -- multi-antibiotic resistance. For Klebsiella vaccine, for example, so we have a lot of derivations from that research. We have the possibility to create new hybrid, for example, artificial glycans, which will cover several of the natural glycans of the surface of the bacteria. And that's what we are applying for Klebsiella. Behind that, we have Gonorrhea and we are working also on additional technologies, which are very promising.

I have one other question, which is on the SLE readout. I think you said one of the Phase IIIs might be this year. So just on the -- I think you said is a S1P mechanism, I just want to understand because there's been a lot of developments in SLE, like BAFF receptor CD40. So thinking about what we should expect to see there from you in the Phase III and why S1P might be a better target than some of the other mechanisms that are being explored.

Well, we have our partners, Viatris in the room today? But Martine, I think you were pivotal in sort of designing the Phase III program. Do you want to talk a little bit about that?

Your question was on the machanism of the Phase III readout?

Mechanism [Technical Difficulty]

Mechanism is very, very interesting. It's very broad. We are-- cenerimod is able to target basically a combination of what all other approaches are doing. And therefore, the results have been very promising for now and Viatris is now into Phase III trials in systemic lupus and lupus nephritis, I believe.

The Viatris presentation yesterday had a very thorough sort of on that one. And we appreciate that Viatris is this scale and the ability to move this one forward -- moving this innovation forward to patients. So they're right in front of you. You can grab them.

Any other questions?

Thank you for the time, everyone. We're looking forward to keeping you posted in Idorsia's progress and hopefully we will be back next year.

Thank you so much.

Good day and thank you for standing by. Welcome to Idorsia's TRYVIO Investor Q&A Webcast and Conference Call.

[Operator Instructions]

Please be advised that today's conference is being recorded. I would now like to hand the conference over to Idorsia's Chief Executive Officer, Srishti Gupta. Please go ahead.

Thank you, Nadia. Good afternoon and good morning, everyone, and welcome to our webcast to discuss TRYVIO and its role in the treatment landscape for difficult-to-control hypertension. After decades of limited progress in hypertension research, we are now entering an exciting new era, led by TRYVIO, the first innovation in hypertension in over 2 decades. It is the first and only hypertension therapy to target the endothelin pathway.

Ahead of the European Society of Cardiology, ESC, meeting, we published an on-demand investor webcast, sharing our perspectives on TRYVIO's ability to address a significant unmet need and difficult-to-control hypertension. Since then, we've engaged with leading hypertension experts at both ESC and the American Heart Association's Hypertension Scientific session. We've also met with many of you in the investor community as the back-to-school season kicks off in the U.S.

Today, we'll address the key questions we've been hearing in those discussions and then open the lines to take your questions on TRYVIO. Joining me are Martine Clozel, our Chief Scientific Officer and a recognized leader in the endothelin system; Alessandro Maresta, Global Medical Affairs Therapeutic Area Head for cardiovascular, renal and metabolism; Michael Moye, President of Idorsia's U.S. Operations; and Julien Gander, our Chief Legal and Corporate Development Officer.

Next slide, please. Before we begin the Q&A, please note that our remarks today include forward-looking statements informed by our research, physician feedback, advisory boards and market insights. As always, we encourage you to consider both risks and opportunities when evaluating Idorsia.

Next slide, please. TRYVIO in the U.S. and JERAYGO in Europe represents the first systemic hypertension treatment to target a new pathway in more than 30 years. This pathway is the endothelin pathway. That brings us to the key question investors are asking. Why is addressing the endothelin pathway such a meaningful innovation and differentiator in hypertension. Martine, can you share your perspective?

Thank you, Srishti. Endothelin upregulation is a central driver of hypertension. It plays a role at very early stages of hypertension during the progression of hypertension and at the stage of end organ damage in hypertension. But endothelin upregulation has remained unaddressed until TRYVIO. The fact that endothelin regulation was left unimposed up to TRYVIO explains why so many hypertensive patients, despite their treatment or combination of sometimes many antihypertensive drugs, could not be controlled, and their blood pressure remained higher than the target blood pressure threshold. This was particular true for certain groups of patients whose hypertension is not obviously difficult to control: African-American, elderly, postmenopausal women, obese patients, and those patients with CKD type 2 diabetes, heart failure or sleep apnea, all of which are actually associated with endothelin upregulation.

Endothelin probably also explains why the patients with difficult to control hypertension are at higher risk of death, strokes and renal failure, almost double the risk compared to well-known -- to well-controlled patients. Indeed, endothelin is a multifunctional peptide, via both its receptor, ETA and ETB, it promotes vasoconstriction, vascular and cardiac hypertrophy, fibrosis, inflammation, catecholamine release, aldosterone release and is increased by salts, thereby mediating high blood pressure, endothelial dysfunction and organ damage.

Aprocitentan blocks the actions of endothelin via both its receptors and therefore, is a multifaceted drug. In healthy volunteers with no underlying disease, even doses 50x higher than the therapeutic dose up to 600 milligrams, TRYVIO had no effect on blood pressure. TRYVIO is only active on an upregulated endothelin system like in hypertension. We proved this in Phase II and in Phase III. The lack of interference with physiology explains its very good safety and tolerability in pathology.

Thank you, Martine. That's very clear. Endothelin plays a key role, it's not been tackled until now. And by targeting the endothelin system, TRYVIO is bringing a completely novel and different approach to patients with hypertension.

Alessandro, let me turn to the PRECISION study. This was a registration trial with the design agreed upon with the FDA. Can you walk us through the key highlights from that study and what they mean for TRYVIO?

Of course, Srishti. First of all, I would like to mention that the compelling efficacy and safety of TRYVIO is well established in labeling and further reinforced by its recent inclusion in the ACC AHA hypertension guidelines. So TRYVIO achieved a meaningful reduction in blood pressure within 2 weeks. This is very important in patients with resistant hypertension that are at risk of cardiovascular events, and the blood pressure was sustained over 48 weeks with a decrease of 19 millimeters of mercury by the end of the study.

Talking about resistant hypertension, the design of the Phase III PRECISION study was especially rigorous with an 8-week running period, a standardized triple fixed dose background therapy with confirmation of compliance and inclusion of only of patients with true resistant hypertension. This trial enrolled high-risk subgroups where classical anti-hypertensive are least effective, including Black patients, all the adults, postmenopausal women, obese patients and those with chronic kidney disease, diabetes, heart failure or sleep apnea, all conditions, as you heard from Martine, associated with endothelin overactivity.

Looking at safety. TRYVIO was well tolerated with only 2 treatment-related side effects, mild early and transient edema and a modest expected decrease in hemoglobin. No direct drug interaction observed a significant advantage for patients on multiple therapies like antihypertensive patients. Importantly, no signal we've seen for hyperkalemia, hypotension, headaches nor heart rate increase. Finally, the label that the FDA approved is based on the totality of the data for adults whose blood pressure remain inadequately controlled on other antihypertensive, a broader population compared to enrolled -- in the one enrolled in PRECISION. In addition, the label includes the relevance of lowering blood pressure for reducing the fatal and nonfatal risk of cardiovascular events, especially strokes and myocardial infarction.

Alessandro, people can follow the on-demand webcast to get more details on the data for TRYVIO. But as a cardiologist, can you perhaps give us some context on the current landscape for not well-controlled hypertension?

Sure, Srishti. So today, paradigm in hypertension relies on a different classes of antihypertensive, of those addressing the renin angiotensin aldosterone system, calcium channel blockers and diuretics, which by the way, they stimulate the RAAS system. But if blood pressure remains uncontrolled, a mineralocorticoid receptor antagonist such as spironolactone can be added, but many patients do not tolerate it, mainly due to hyperkalemia, worsening of renal function, gynecomastia and in addition, we observed a high discontinuation rate.

So despite all the classes of antihypertensive drugs, millions of patients remain uncontrolled and TRYVIO offer a solution with a completely new mode of action.

Thank you, Alessandro. That certainly highlights the significant unmet need that a safe and effective drugs like TRYVIO can address in the current landscape. What about compounds in development?

Yes, Srishti, there are several products in development, but most of them are still targeting the RAAS system, including the aldosterone synthase inhibitors. These drugs are still in development, and we don't know yet what their label will look like. But what we know is that the studies were not as robust as PRECISION in enrolling true resistant hypertension patients. And there are safety concerns such as hyperkalemia, hyponatremia and decrease in renal function, particularly if combined with other drugs that are targeting the RAAS system. And this is where TRYVIO stands apart. It addressed the endothelin pathway, a fundamental driver of disease, that other treatments don't reach with a proven efficacy and a good safety and tolerability profile.

So TRYVIO is differentiated to the current and potential emerging treatments. Which patient populations do you see TRYVIO being used for?

So if we take into consideration the new mode of action, the efficacy and safety profile and the FDA granted label, TRYVIO is the ideal choice for many patient groups. I can list for you some: patients with risk factors for hypertension, which will be difficult to treat because they are endothelin-dependent; black, elderly obese patient, patients with sleep apnea, type 2 diabetes, early heart failure and chronic kidney disease. Then we have patients that are not adequately controlled despite 2 lines of hypertensive therapies and patients who cannot tolerate certain classes of drugs because of their side effects.

There are also the patients that we have studied so they're truly resistant hypertensive patients that are not controlled despite treatment with 3 or more therapies at their maximum tolerated dose. And then I would like to tease out the patients with chronic kidney disease stage III and IV and resistant hypertension because for these patients that have currently no alternatives. In all these patients, TRYVIO represented an obvious choice with very little competition.

Thank you, Alessandro. So there's a large addressable population of patients with hypertension that is not adequately controlled. Michael, given that the U.S. market is essential to realizing TRYVIO's full potential, can you walk us through the key drivers that support our $5 billion peak sales estimates?

Yes. Thanks, Srishti. Our forecasts are grounded in extensive market research and analytics to understand both the size of the opportunity and how physicians intend to use TRYVIO.

Next slide, please. So today, of the 40 million treated patients in the U.S., there are roughly 26 million patients treated with 2 or more therapies. And 30% to 50% of those are inadequately controlled despite receiving treatment and therefore, eligible for TRYVIO according to the FDA label with the only contraindication being pregnancy and sensitivity to aprocitentan. This population is expected to grow, given the aging demographics, higher rates of comorbidities linked to endothelin function and increasing recognition of the severe consequences of uncontrolled hypertension.

Importantly, these consequences are already reflected in the FDA indication that removes any need for a separate outcome study. We estimate that around 7 million patients as we move to the middle of the slide -- the 7 million patients are easily identifiable and are well defined a good area to focus on first coming into the market. Patients with endothelin-driven comorbidities often face restrictions with other therapies. Chronic kidney disease, as you've heard, is a prime example -- it's a prime example. Patients with hypertension and CKD are often treated with 2 or more agents yet few effective options exist.

TRYVIO is approved for patients with an eGFR as low as 15 and has demonstrated excellent safety and tolerability with no hyperkalemia and no hypotension. Other identifiable groups include patients who can't tolerate certain classes of drugs and those with true resistant hypertension. So we now have real-world efficacy and safety outcoming the mirror of what we saw in PRECISION.

These drive adoption and penetration assumptions. So as you can see, they range here from 12% to 22%. So our insights are informed by over 1,000 qualitative and quantitative interactions with multi-specialty physicians, including top hypertension centers. Physicians consistently recognized TRYVIO's efficacy, safety and its unique mechanism of action when they're addressing -- that address what additional RAAS blockade cannot. In comparison with emerging therapies, TRYVIO is viewed favorably by these physicians, particularly for patients with CKD and based on the impact on both blood pressure and uACR measures.

And finally, the payers, which we know are all very important, have responded very positively, highlighting the robust primary endpoint of more than 15-millimeter drop from baseline, the statistical strength and the sustained efficacy through the duration of the PRECISION study as very compelling reasons for coverage. We have set a WACC at $775 a month and we're focused on a very favorable gross to net as a first-in-class differentiated therapy. TRYVIO is currently being reimbursed with reasonable utilization management criteria, which supports our commercial model. Srishti?

Thank you, Michael. Beyond the U.S., we also see an additional upside from geographic expansion. Aprocitentan has already improved at JERAYGO in the EU and the U.K., and there is significant opportunity in Japan and China. We also see that we can get further value through IP extension strategies, for example, with fixed-dose combinations with the SGLT2 inhibitors and indication expansion such as exploring renal protective benefits in CKD. Of course, realizing the full potential of TRYVIO will depend on securing the right partner, which is why we're actively engaged in these discussions at this time.

Julien, could you share a little bit more about how we're thinking about partnering discussions?

Yes, happy to. Look, we've been very consistent in saying that we lead where we demonstrate scientific or commercial advantage and strategically partner where external expertise, scale or speed adds value. So specifically on TRYVIO, partnering TRYVIO remains a key strategic priority for us. We are actively engaged in discussions with potential partners, which reflects the interest in the assets and the opportunity TRYVIO represents. While this process takes time, we're encouraged by the progress and look forward to updating you as we move forward.

In the meantime, I can tell you, we continue to work very diligently and at high speed to maximize the value of TRYVIO. We've seen some of this in the past weeks and months. I think of the REMS removal, the collection of early, very positive real-world experience, the inclusion of TRYVIO in the ACC AHA hypertension guideline. And very recently, the recent initiative announced with Duke and Stanford University.

Thank you, Julien. Having addressed some of the key questions that we have received around TRYVIO, I think it's a good time to open the lines for additional questions. Nadia, can you please go to the next slide and open the line, please?

[Operator Instructions]

And we're going to take our first question. It comes from the line of Joris Zimmermann from Octavian.

This is Joris Zimmermann from Octavian. I have two questions. One will be on partnering that you just highlighted, Julien. Is there any timelines you could give us? Or at least do you still expect to close a deal this year? And then the second question would be until you have found the right partner and signed an agreement, and given the limited resources you can currently deploy in the U.S., where will you put your focus in terms of the aprocitentan launch.

Thank you, Joris. Julien, will you respond to the questions?

Yes, very happy to. Thank you, Joris. Look, I mean you will understand that we cannot really comment on specific timelines. But what I can say, and I can ensure that the partnering aprocitentan is really a key priority for us. And to your point, we resource this project accordingly. We, of course, want to move very quickly and also considering the time advantage we have towards emerging therapies. But you will understand that actually, our focus is not only just speed, but it's also securing the right partners to maximize TRYVIO commercial success.

To your second point, Idorsia is indeed has limited capacities, but I think considering these constraints, we've done a lot to make sure that the product is advancing, is prepared to be launched. And the product is commercially available, and we have very good early evidence, and we'll continue those efforts, and we are hoping to give you an update as soon as we can on achieving this goal of partnering.

Thank you, Julien. Michael, maybe I'll have you add to that with your presence at the AHA -- recent AHA meeting and some of the other work that we're doing on retail distribution.

Yes. Thanks, Srishti, and thanks for the question. Yes, we -- despite these -- the resource constraints, we are quite busy continuing our kind of launch and market prep. So Srishti, as you said, we're at the major congresses. So we have a really strong presence there. We're working with a lot of the top KOLs and a lot of the top hypertension centers. You heard about the Duke, Stanford relationship that come out. We are -- have really finalized a lot of the core materials. So we have a full digital presence. Our consumer and HCP websites are up and running. We've got print materials and things out there.

And then the last couple of things. We're continuing our payer discussions, which continue to go really well. And then as Srishti made reference to at the end, the pharmacy distribution. So once the REMS was removed, we're able to move in addition to having a specialty pharmacy, we are quite literally right now coming online with full retail distribution across all retail pharmacies in the U.S. So yes, despite the resources, we're making great progress, again, across KOLs, congresses, payer discussions and pharmacy distribution. Srishti?

Thank you, Michael. Nadia, we'll take the next question.

[Operator Instructions]

We have a follow-up question from Joris Zimmermann from Octavian.

Okay. Sorry. I hope I didn't jump the line now. But two more questions. I mean you talked about the patient populations and that you see a very broad target population. But maybe you can give us an idea based on this broader label that you got versus the study inclusion criteria, what are the kind of -- where do you see the quickest uptake in the market? Which type of patients do you think will be the ones that physicians consider prescribing aprocitentan first? And then also, maybe you could give us a little bit an idea of the hurdles that you foresee as well.

Joris, thank you for the question. Michael, would you like to walk a little bit through how we think about the targeting of the patient populations in the U.S. and how we might access them with the centers of excellence.

Yes. So when we look at that and we look at both our research and our interaction with the physicians, we're definitely seeing the data across all the subgroups has been one of the things that's jumped out of physicians. So you heard a little bit in our opening that clearly, the CKD is a differentiated piece and that we see that as a great opportunity. The other thing about the subgroups that we're seeing kind of across these multiple comorbid patients, you heard about patients challenge with hypertension management, black patients, obese patients, again, patients with CKD.

The thing about the profile that continues to jump out is the fact that we don't -- we have efficacy and safety across all these subgroups. We don't have any real exclusions or contraindications and especially we don't have any drug-drug interaction problems, obviously, with these patients being on multiple medications.

So when we think about those different subgroups and those comorbid patients that are at more risk, including the CKD patients, we see consistently the one pill, one dose, once daily, good tolerability, no drug interactions. That allows -- those factors are what the physicians are pointing out to us that allow us to treat these high comorbid risk subgroups.

Thank you, Michael. And Joris, in terms of your second question, I'd like to turn it over to Alessandro. Alessandro has been attending a lot of the KOL meetings in all over the United States over the last couple of months, meeting physicians, understanding how they think about TRYVIO. So Alessandro, can you talk a little bit about how you think about the hurdles that physicians are thinking about as they are deciding on prescribing TRYVIO.

Thank you very much, Srishti. I think that, in my opinion, the best -- the most important hurdle is the new mode of action. The physicians are used to the RAAS system, are used to calcium channel blockers and now they need to realize and understand that there is a new kill of the block that is an endothelin receptor antagonist, and that endothelin receptor antagonist can be very, very beneficial in the subgroup of patients that I and Michael highlighted.

So basically, I see this as the major hurdles because the results are really impressive. The safety profile is also very, very good. And we have a clear understanding on which are the patients that would benefit the most from this -- from TRYVIO. And last but not least, there are many, many patients that despite they add on 2, 3 or even 4 drugs, they are still not at goals. And these patients, they need -- they deserve treatment. So I don't see many hurdles in front of us.

Alessandro, thank you for that. And it underscores the importance for us of finding a partner who can help us on the broad outreach and the medical education required to enhance the importance of the end -- addressing the endothelin upregulation that occurs in a lot of hypertension. So this is definitely something we are thinking about and focused on as we move forward. Joris, thank you for the questions again.

Thank you. Dear speakers, there are no further questions for today. I would now like to hand the conference over to your speaker, Srishti Gupta, for any closing remarks.

Thank you, Nadia. So this concludes today's call. Thank you for joining us and for your continued interest in Idorsia. Our next scheduled update will be on October 30 when we report our third quarter results and will provide a comprehensive update on QUVIVIQ performance. Operator, you may close the line.

This concludes today's conference call. Thank you for participating. You may now all disconnect. Have a nice day.