Idorsia Ltd

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.

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.

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.

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.

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?

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.

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.

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.