Idorsia Pharmaceuticals Ltd

Good day and thank you for standing by. Welcome to the Eidosia Full Year 2025 Financial Results Conference Call and Webcast. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be the question and answer session. To ask a question during the session, you need to press star, one, one on your telephone keypad. You will then hear an automatic message advising your hand is raised. To withdraw a question, please press star, one, and one again. Please be advised that this 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 Grunewald, 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 Idorsio-led QVIVC sales for 2025 have more than doubled compared to 2024, rising from 60 million to 134 million Swiss francs, just above our target, which we upgraded in May last year. This performance was a result of strong commercial traction and growing demand for QVIVC 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 308 million Swiss francs to a loss of 100 million. Key to this operational recovery has been our commercial strength paired with cost control. Arna will share more on our financial performance later. Next slide, please. Adorsia represents a rare combination of valuable assets. We are a commercial stage pharma company with two 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 Q-Vivic the standard of care in insomnia. In parallel, we are actively engaging in partnership discussions to maximize the value of Trivio-Durigo 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 Q-Vivic. As you know, Qvivik 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 Qvivik offers restorative sleep and revitalized days. Before we talk about the commercial performance of Qvivik, it's important to ground ourselves in the patient experience of insomnia. Infamia 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 QVIVIC in 2026 as we guide to sales of around 200 million Swiss francs. 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 QVIVIC 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, Tubavik is the only pharmacological treatment for long-term management of insomnia disorder. Our three-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 continued 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 Menorini in France in October 2024. and Germany in April 2025. And in February 2026, we added the UK. 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 results of these efforts has been an outstanding trajectory, particularly in France, but closely followed by Germany, the UK, 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 UK. Next slide, please. In the U.S. in 2025, we executed a targeted digital marketing strategy with Zinio's Health to stabilize sales and maintain our core patient base. Going forward, ensuring more patients have access to Qvivic remains a priority. To achieve this, we are advancing three 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 QVIVX 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 Cuvivic'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. Cuvivic is available in Japan through our partner, Nexera, and they recently saw positive phase three results in South Korea. Our partner, Sincere, has had a very strong uptake in China, within the private setting with three to 400,000 patients treated within the first six months. In June, we signed the licensing and supply group with CTS in Israel and more recently in 2026 with EMS in Latin America. In Brazil, the regulatory dossier has been submitted to NVISA 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 daridurexan, 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. Diredurexan is the only DORA in pediatric development, and as a 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 Aprocitantan, commercially available under the trade name Trivio in the U.S. and Gerigo in EU. We secured regulatory approvals in the UK, Switzerland, and Canada during 2025. It is the first and only endothelial 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. TrivioGerigo 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 three, four, 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. APROSI 1010 delivered a double digit blood pressure reduction of 15.4 millimeters of mercury in just four weeks, on top of a standardized triple therapy administered as a fixed dose combination pill. APROSI 1010 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 decline in EGFR. The FDA approval provided a broad U.S. label that indicates Trivio is suitable for use in all patients who are not adequately controlled on other therapies, with the cardiovascular outcome benefits cited within the indication statements. Trivia benefited from several important de-risking milestones in 2025. In March, the FDA removed the REMS requirement, simplifying prescribing and distribution. Then in August, a ProC1010 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 Trivio is a compelling and differentiated option for these patients. Market access work for Gerigo is also underway in Europe to support our partnering efforts. Next slide, please. Thrivio 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 Trivio across diverse comorbid patient types. Trivio'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 two 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 three or more therapies, truly resistant to 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, Trivio 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 three 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 the 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 leucerous dot 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 FABRI 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 a uniquely differentiated option in a market expected to reach $4 billion U.S. dollars. The body of evidence we have generated to date shows that long-term treatment with Lucerostat consistently reduces the glycosphingolipid substrates that accumulate in FABRE disease. We also observe 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 glycosomal deposits. for 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 Lucerestat. 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 the serostats potential as the first oral monotherapy suitable for all FABRE 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, Christy. Good afternoon and good morning to everyone on the call. In my first slide, you can really see the impact of our increased QVC sales and contract revenue. together with our cost saving measures, resulting in a significantly improved operating results. Net revenue of 214 million includes 134 million from QVivec product sales, excluding partner sales. A significant increase compared to the 61 million of sales in 2024. The main driver of the sales increase is the EU-Can region, where sales increased from 32 to 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 de-scheduling. Non-GAAP contract revenue of 72 million includes the 35 million U.S. dollar exclusivity fee from the undisclosed partner for Aprocitantam that was received in Q4-24 but recognized in Q125 after the exclusivity period ended without resulting in the deal. As a reminder, the undisclosed partner was not able to close the deal for reasons absolutely unrelated to our proceedent time. In addition, we received a 40 million Swiss franc signing and approval milestone from CIMSIR related to the outlicensing of QVVIC in China. The cost rationalization efforts initiated in 2024 and 2025 further improved our operational cost base with savings of more than $80 million compared to 2024. As a result, the non-GAAP operating results improved from a loss of $308 million in 2024 to a loss of $100 million in 2025. Based on successful negotiations with Viatris in Q1 2025, Eidosia's cost-sharing commitments were reduced by 100 million US dollar against a reduction of potential future regulatory milestones. This resulted in a gain of 90 million Swiss franc. Other non-gap-to-gap differences mainly include depreciation and amortization and stock price compensation. This resulted in a US gap EBIT loss of 33 million. The US GAAP net loss of $112 million also includes the financial expenses of $72 million, which also includes a $61 million non-cash expense related to the convertible bond restructuring and the new money facility. And we had an income tax expense of $6 million. Next slide, please. In addition 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 106 million in cash. Operational cash inflows included 142 from QVV product sales, including sales to partners, and operational cash outflows included 250 million of SG&A and 93 million of R&D costs. The 11 million other cash outflows mainly included working capital movements. Further, as announced in May 25, we secured a 150 million Swiss franc funding facility from our bondholders. And in June 25, we drew the first tranche of 70 million. We also raised 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 over subscribed demand from the top tier institutional investors that participated in the book building process. This resulted in a liquidity of $8 million at the end of the year. And in addition to that, we still have access to a further $80 million from the new money facility, which totals $169 million liquidity available to Eidosia. 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 reflection 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 cumulative sales of 134 million exceeded the guidance sales of 130 million due to an excellent execution of our commercial strategy, as we 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 US GAAP operating loss or US GAAP loss of 33 million is lower than the guidance mainly due to one of lower stock price 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 IDOR-CLF sales excluding sales to partners because this is the performance that we can actively steer and have control over. We expect a continuous QMVIC sales growth, and with sales of 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 two approved products with significant commercial potential and a pipeline of first and best-in-class compounds, IDORCEA is positioned to create meaningful value. I am proud of the team's performance in 2025. We delivered on upgraded ambitious guidance, accelerated Qvivix commercial trajectory, and continued building the foundation for long-term growth. Travio-Gerigo 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.

Thank you so much. Dear participants, as a reminder, if you wish to ask a question, please press star 1-1 on your telephone keypad and wait for a name to be announced. To withdraw a question, please press star 1-1 again. Mr. Bauer will compile the Q&A or studies. We'll take a few moments. And now we're going to take our first question. And it comes to the line of Raghuram Selvaraju from HC Wainwright and Co. Your line is open. Please ask your question.

Thank you so much for taking my questions. Firstly, I was wondering if you could elaborate a little bit further on the digital distribution model for Q-Vivic, 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 QVivic 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 timeframe within which you would want to have a Trivio-Jurago 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 Tri-V or Gerigo, or is that going to be entirely driven by organic growth in the internal products over which you maintain commercial control? Thank you.

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 QVIVC. Is that the first question area? And so 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 be able to go 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 Qvivic. We've heard, you know, 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 Qvivic. 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 Trivio available through that model, it might actually have an impact. But right now, the current focus really is Q-Vivic, especially because we have more experience with Q-Vivic and understand the points of friction that were there for patients and prescribers. So then moving on to your second question area of Trivio and the ideal timeframe for a partnership in the U.S. With the approval and the availability of Trivio 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 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, you know, 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 Walgreen's 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, you know, as we find that partner in the U.S., that they are able to make Trivio 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, 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, you know, 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.

Yeah, 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 guys were 26 and in particular the growth of QVIVX sales, we are really making clear steps to profitability and cash flow break even. that 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 Christy said, I mean, going forward, we will limit our guidance to the current year. There's 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.

Thank you.

Next question.

Yes, of course. Now we're going to take our next question. And the question comes line of Joris Zimmermann from Octavian. Your line is open. Please ask your question.

Yeah. Hi, everyone. This is Joris Zimmermann from Octavian speaking. Thank you so much for taking my questions. Two, if I may. First, on the QVBIC 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 come with a pediatric extension as well? So that would be on QVivic. And then the second question on your cash and cash reach with the current cash of around nine million Swiss francs and the 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? Thank you.

Thank you for joining, and thank you for the questions. I'll take the first one in hand. It's the second one over to Arnaud. On the pediatric Q-Vivic daridorexan study that we're expecting in Q2 2026, it's a dose-finding study. So we tested in three doses, and we'll do a dose-response curve. And so what we're expecting, hopefully, to see is both positive results with daridorexan 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., the FDA, as well as the EMA. So, you know, we would have to run a Phase III program. We're expecting to be running a Phase III program, but we would like to shape that program, you know, based on the findings of the Phase II. 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 DORAs with the safety profile that is 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 The other part of it for me that's very exciting is that there's, you know, 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, you know, 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 Arnaud.

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 169 million, we clearly have sufficient cash to bring us to the next inflection points. And as already mentioned by Sristi with the previous question, I mean, there are many variables and inflection points to come. So that will also clearly have an impact on... on our cash needs 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.

Next question. Thank you. And now we're going to take our next question. And the next question comes from Neil Alexander from Deutsche Bank. If the line is open, please ask your question.

Hi, it's Neil Alexander from Deutsche Bank. Thank you very much for taking my question. So I guess maybe just moving to the pipeline, just on your CXCR7 antagonist in MS, I understand it is just a proof of concept right now, but it would be helpful to understand how you feel this mechanism could potentially be differentiating, especially so to the likes of the CD20s right now, or even the BDKs 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 IL70s and 23s in the space. Thank you very much.

Thank you, Neil, 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 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 as well as 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 cleaner 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 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 to be able to transform the treatment paradigm in the 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 imaging, yeah, via imaging, we can see a slowing of the demyelination. And so, that's kind of the proof of concept that we've designed for the CXCR7.

Understood. Thank you.

Thank you so much. Now, we're going to go to the next question. And the question comes from . Your line is open. Please ask a question.

Hi. This is for Shashida. Thank you for taking our questions. We have two. First, could you provide more of an update on the QVIP scheduling process, like how likely is it that it will happen this year? And second, on the Saturday 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, and 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 ADORA across the globe between Japan, China, and Europe, and there's a couple million patients in the U.S. And we consistently know that QVIVC 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-US data. This is on top of, you know, 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 non-scheduled 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 de-scheduling to unlock the value of Qvivik 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 the model on direct-to-patient to be able to accommodate for the current schedule, as well as then expand based on any de-scheduling that happens. So we are really focused on making sure that even in its current form that we can increase access for patients as they can have the benefit. And then, of course, all of those things in total, as we get more and more patients on COVID, 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 Fabre, 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. Perfect.

Thank you so much. Did I answer? Yeah. Yes. Perfect. Thank you.

Thank you so much. Dear participants, as a reminder, if you wish to ask a question, please press star 1 1 on your telephone keypad. And now we're going to take our next question. And the question comes to the line of Myles Minter from... Hi.

Thanks for taking the questions. 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 ART and fat breeds. And then I noticed at the World Symposium, you seem to see a greater efficacy signal in patients with, you know, pretty severe declines in EGFR at baseline and also anti-drug, antibody-positive patients on the ERT side. So I'm just wondering whether you're going to stratify that. 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. Thanks very much.

Miles, 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, you know, 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 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 FABRE, 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 from Modify, that was 43 months, which was, I mean, I think six years, right? Like we're in total with the six-month Modify trial. That's six years. I mean, 50% is actually a really good retention rate after six years. I don't know if there's anything I'm doing right now that's – the same as I was doing six years ago. So, I think that retention rate actually seems pretty good for this type of study for a chronic, for a daily oral and with a chronic, for a chronic condition.

Great. Thanks for the questions.

Thank you. Now, we're going to take our next question. And the question comes line of from Octavian. Your line is open. Please ask your question.

Thank you. One more question from my end on the opposite end on 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 guideline. So I was wondering, what is it that is kind of – why do the proceeding on partnering discussions still go on? Can you maybe comment on that? So is it more on the finding the right partner in the US 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 third question, actually. So, I mean, you It'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, you know, 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 endothelial 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 where having a commercial asset that has not had the ability to be resourced for a launch that's a new mechanism of action that needs to be introduced in a pretty complex healthcare 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 Tri-VO gets to the patients and are willing to put the effort to make sure that Tri-VO 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 three or, you know, at this de-risking stage where they can prepare the market. And so I think right now we're just, you know, in a peculiar stage with Trivio, but we are actively engaged in a range of conversations. I think one last point to make is that the 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 partnerships. We have two different labels, two different brands, two doses for Trivio-Durigo, 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.

Thank you.

Thank you, guys. 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 28th. 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.