Good day, and thank you for standing by. Welcome to the Idorsia Unlocking the Value of TRYVIO/JERAYGO 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 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 today's conference is being recorded. I would 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 investor webcast. My name is Kevin Boss, Director of Investor Relations at Idorsia. Last week, we announced a proposed commercialization partnership between Idorsia and the SPV noteholders to unlock the blockbuster potential of TRYVIO/JERAYGO. Today, we have members of management with us to walk you through our strategy, why now is the right time, and why this represents an attractive use of capital for Idorsia. 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 our new CEO, Roland Wandeler. Next slide.
Good morning and good afternoon, everyone, and thank you for joining us. As this is my first investor webcast since becoming CEO of Idorsia, let me begin with a few reflections from my first four weeks in the role. Over the past weeks, I have spent my time listening, learning, and building my own understanding of the opportunities in front of us. I have met colleagues across the organization, reviewed our commercial portfolio and pipeline in depth, and spoken with physicians, partners, and investors. Across those conversations, I have been looking for the opportunities that can create the greatest impact for patients and the greatest value for shareholders. I joined Idorsia because I believed the company possessed assets of exceptional quality.
What I have seen over these first four weeks has only strengthened that conviction, and I am even more convinced today than when I accepted the role that we have significant unrealized value within our portfolio. What stands out to me is that the opportunity in front of us is increasingly about execution. We have differentiated medicines. We have attractive growth opportunities. We have a proven innovation engine. The challenge now is not to redefine our strategy. The challenge is to execute against it with focus, discipline, and urgency. And there is perhaps no better example of the value this company can create than today's announcement that daridorexant has received FDA breakthrough therapy designation for insomnia in children and adolescents. To me, this recognition reflects both the strength of our science and the significant opportunities that remain ahead of us. Next slide, please.
At our mid-year results, we outlined four key drivers of future growth and value creation for Idorsia, and those priorities remain unchanged today. What matters now is execution. The four growth drivers we shared, together with a disciplined capital allocation, remain the right framework for value creation. My role is to ensure that we execute against them with focus, discipline, and urgency. The first driver is continued growth of QUVIVIQ, building on the momentum we see across markets, including promising signals in the U.S. The second is unlocking the value of TRYVIO and JERAYGO. The third is expanding the value of daridorexant beyond sleep through development in autism spectrum disorder. The fourth is advancing the next wave of innovation from our pipeline. Together, these four drivers provide a clear framework for how we intend to create value over the coming years.
Today's webcast focuses on the second of those drivers, unlocking the value of TRYVIO and JERAYGO. Over my first weeks at Idorsia, together with QUVIVIQ, this is one of the opportunities I have spent the most time evaluating. What I have learned has led me to a clear conclusion: the opportunity is more compelling today than many appreciate. Let me explain why. Next slide, please. When evaluating a commercial opportunity, there are three questions that are critical: Is the medical need significant? Is the product differentiated? Can that differentiation be translated into commercial success? For TRYVIO/JERAYGO, I believe the answer to all three questions is yes. First, the medical need is substantial. Millions of patients living with hypertension remain uncontrolled despite treatment with multiple antihypertensive therapies and continue to face elevated risks of serious cardiovascular and renal complications.
What I have heard consistently from physicians is that many of these patients still need additional treatment, particularly those with complex comorbidities such as chronic kidney disease and diabetes, where treatment options are limited. Second, the product is genuinely differentiated. TRYVIO/JERAYGO is the first and only dual endothelin receptor antagonist approved for systemic hypertension. Importantly, this medicine introduces a new and orthogonal mechanism of action, targeting a pathway that has not previously been addressed in hypertension. Combined with compelling efficacy and safety, as well as broad applicability across patients whose hypertension is difficult to treat, this creates a highly differentiated profile. Third, we believe this differentiation can translate into meaningful commercial success. Over the last four weeks, I have spent considerable time reviewing this opportunity, reviewing the available data, challenging assumptions, and listening to both internal and external perspectives.
What I have learned has led me to the clear conclusion that the opportunity in front of us is more compelling today than it was at launch, and more compelling than many appreciate. What gives me confidence is not a single data point. It is the consistency of what we are seeing across multiple indicators. It is the combination of increasing physician awareness, growing recognition of the unmet need, a clear understanding of where the product creates the greatest value, and encouraging early experience in the U.S. That has led us to what I would describe as a disciplined fast follower strategy. We are not attempting to compete head-to-head with large pharmaceutical companies across the entire hypertension market. Instead, we are focusing on clearly identified patient populations at launch, where TRYVIO's differentiation is strongest, and where we believe we can create significant value with a focused deployment of capital.
As awareness of difficult-to-control hypertension continues to grow, we believe we can benefit from many of the broader market development efforts already taking place, while concentrating our own efforts on the patients and specialists where we see the greatest opportunity. In my view, the combination of significant unmet need, a differentiated medicine, increasing market readiness, and disciplined execution creates a compelling path towards blockbuster potential. The conclusion I have reached is straightforward. This is an opportunity that merits investment, and now is the right time to make that investment. The financing proposal we are discussing today is designed to make that investment in a disciplined and focused manner. Importantly, we believe the ultimate opportunity may be substantially larger than what is reflected in our current plans. The financing proposal is not intended to realize the full potential of TRYVIO overnight.
Rather, it is designed to accelerate the next phase of growth, generate additional evidence and experience in the market, and establish a clear path toward building a blockbuster brand. Next slide. To help explain why our conviction has strengthened, I would like several of my colleagues to share their perspectives. First, Martine Clozel will discuss the scientific foundations of the endothelin pathway and explain why we believe this biology represents an important and differentiated opportunity in hypertension. Next, Amer Joseph will explain what this science means for physicians and patients in everyday clinical practice. Following Amer, Rudy Sharan will discuss what we have learned from the market and how early physician experience in the U.S. has strengthened our confidence in the commercial opportunity.
Finally, Arno Groenewoud will explain the proposed funding structure and why we believe it provides a disciplined mechanism to accelerate value creation while aligning stakeholders around long-term success. With that, let me hand over to Martine. Next slide, please.
Thank you, Roland. We now understand better the crucial role of the endothelin pathway in hypertension and why TRYVIO/JERAYGO can transform the treatment of hypertension when blood pressure is difficult to control on other drugs. Next slide, please. Endothelin had been described by Masashi Yanagisawa in his very first paper in 1988 as the most potent vasoconstrictor ever known, but it is much more than that. Endothelin and its receptors, ETA and ETB, form a tissue-like system within arteries, heart, kidney, and other organs, which is very silent in normal conditions, but extremely powerful when it is stimulated or upregulated, and then induces the many pathological changes which you see on this slide. Endothelin upregulation causes vasoconstriction, vascular and cardiac remodeling, fibrosis, and inflammation in several organs, and these detrimental effects are mediated by both ETA and ETB receptors.
In hypertension in particular, endothelin is upregulated very early, even before hypertension develops, suggesting or indicating causality. Next slide, please. The renin-angiotensin-aldosterone system, which we see on the left, has been the basis of a large number of antihypertensive drugs, from ACE inhibitors and mineralocorticoid receptor antagonists introduced more than 40 years ago, to angiotensin receptor blockers 30 years ago. It is still the main source of development of new drugs, for example, RNA-based angiotensinogen therapeutics or aldosterone synthase inhibitors. However, there are limitations to the extent to which the renin-angiotensin-aldosterone system can be blocked. Since the terrible experience of the renin inhibitor aliskiren in the years 2007 and 2010, which resulted in a contraindication and safety warnings for combinations containing aliskiren, and also led to recommendations against the combination of ACE inhibitors and angiotensin receptor blockers with a second blocker of the renin-angiotensin-aldosterone system.
We learned that too much RAS blockade can increase the risk of worsening renal function, acute renal failure, hyperkalemia, hypotension, and syncope. As we know today, there are no such risks when blocking the endothelin system, and this is why it is so important that aprocitentan targets a different system, separated from the RAS. Aprocitentan is the first antihypertensive medicine to target a completely new pathway in nearly 40 years. Next slide. Many patients with hypertension do not respond to antihypertensive therapies, even in combination of three or more drugs, and remain hypertensive. Because endothelin is so potent and is not tackled by classical modes of action of antihypertensive therapies, we hypothesize that these types of hypertension may be endothelin-dependent forms of hypertension.
Indeed, among the groups of people with hypertension in whom blood pressure remains uncontrolled very often despite treatment, there is an upregulation of the endothelin system in each and every one of them. This is the case of patients with obesity, African American, elderly, sleep apnea, patients with diabetes or kidney disease. The hypertension is very often very difficult to control. Only an endothelin receptor antagonist can antagonize the upregulation of the endothelin system and all of its consequences. Next slide. Why aprocitentan? In our search for the optimal molecule for systemic hypertension in combination with other drugs, aprocitentan was chosen because it fulfills all the elements of our wish list for this indication and for these patients. In particular, there is considerable evidence that blocking both ETA and ETB receptors provides superior efficacy in pathology as compared to selective blockade of one endothelin receptor.
Aprocitentan has no identified drug-drug interaction because its metabolism is not dependent on cytochromes. Its long half-life of approximately 44 hours provides the comfort of a once-a-day drug and a sustained efficacy throughout the day and the night. Aprocitentan elimination is independent of kidney function, so no need to worry about change of dose. The once-daily oral dosing is easy, with no relevant food effect and no risk if a dose is missed. Next slide. The dependence upon endothelin upregulation explains the quite amazing results of aprocitentan in the phase III PRECISION study, where we dared to tackle the most difficult-to-treat patients, those with confirmed resistant hypertension.
In patients with three, four, five, or more drugs at baseline, including 72 on MRAs, spironolactone in particular, and who remained hypertensive, aprocitentan reduced blood pressure by more than 15 mm-17 mm of mercury, with the maximal effect already reached at the first measure of two weeks, proving endothelin dependency of these patients. With that, let me introduce Amer, who will now show what this means for patients with uncontrolled hypertension. Next slide, please.
Thank you, Martine. Uncontrolled hypertension remains one of the most common and challenging problems physicians face in clinical practice. As a cardiologist, I have treated many patients who are doing everything we ask of them, adopting lifestyle changes, taking multiple medicines every day, and returning regularly for follow-up. Yet, their blood pressure remained uncontrolled, and their cardiovascular and renal risk continued to accumulate. Let us now look at what a generally different treatment approach could mean for these patients. Next slide, please. Uncontrolled hypertension is not simply a number that remains too high. It exposes patients, often silently, to a progressively greater risk of stroke, heart failure, kidney failure, and premature death. Globally, more than 1,000 people die every hour from strokes and heart attacks linked to high blood pressure, and most of these deaths are preventable. The impact of better control is crucial.
Evidence from more than 600,000 patients shows that every 10 mm of mercury reduction in systolic blood pressure is associated with a 20% reduction in major cardiovascular events, including a 27% reduction in stroke and a 28% reduction in the risk of heart failure. Yet, approximately 36 million patients across the United States and Europe remain above their target blood pressure, despite treatment with guideline-recommended therapies. The physician is often left escalating therapies that act on biological pathways already being targeted, and what is needed is a distinct mechanism that can deliver meaningful additional blood pressure reduction in these difficult-to-treat patients. Next slide, please. Physicians are therefore looking for a treatment that delivers rapid and durable blood pressure lowering, especially in their most challenging patients. They are looking for a treatment that is straightforward to use every day and can be added without creating additional management burden.
Because hypertension is often a silent disease, tolerability is particularly important. Patients generally don't feel the condition itself, so side effects can become a major obstacle to long-term adherence. Beyond blood pressure reduction, physicians also value evidence of benefit on the complications of hypertension, as these drive morbidity or mortality. In the pivotal PRECISION study, aprocitentan produced an absolute reduction in office systolic blood pressure of 15.4 mm of mercury at week four. This was on top of standardized triple therapy, but importantly, around two-thirds of patients were on four or more antihypertensives, so a truly uncontrolled population. The decrease was observed as early as two weeks and was sustained over the 48-week study period, therefore rapid and durable. The study included patients across almost the full spectrum of CKD, including patients with significantly impaired renal function and several comorbidities.
These are the patients whose blood pressure is often the most difficult to control. Importantly, unlike many treatments that target the renin-angiotensin-aldosterone system, there was no increased risk of hyperkalemia or hyponatremia, eliminating the need for routine electrolyte monitoring. We also observed no increased risk of orthostatic hypotension, providing additional reassurance regarding its tolerability, particularly in older patients. This profile translated into strong treatment adherence, with nearly 90% of patients remaining on treatment over the 48-week study period. As you have heard, the medicine is taken orally once daily, with one 12.5 mg dose in the U.S., and there are no drug-drug interactions. For physicians managing patients already receiving multiple treatments, this simplicity matters, and it allows the introduction of a new mechanism without substantially increasing treatment complexity. Next slide.
The overall study result is important, but physicians also want to know whether the effect extends to the different patients they see in clinical practice. At week 36, what we are seeing here is double-digit absolute reductions in office systolic blood pressure across subgroups, including in patients with stage 3 or 4 kidney disease, patients with type 2 diabetes, Black patients, and older individuals. While these subgroup analyses are exploratory, the consistency of effects across these populations is encouraging. These are precisely the patients for whom treatment is often most challenging and where the benefit of many treatments may attenuate. Yet, these patients are also often those at highest cardiovascular and renal risk. Next slide. Ambulatory monitoring gives us a more complete picture of blood pressure control over the 24-hour period compared to office measurements alone.
This is particularly relevant because nighttime blood pressure is one of the strongest predictors of cardiovascular events. At week four, aprocitentan reduced ambulatory systolic blood pressure during both daytime and nighttime, showing that the effect was sustained over the full 24-hour period. We also observed marked reductions in urine albumin-to-creatinine ratio, a well-established marker of kidney injury, by more than 50%. Large meta-analyses have shown that a 30% reduction in UACR is associated with an approximate 20% reduction in kidney failure. The magnitude of albuminuria reduction you are seeing here compares favorably with those reported with RAS inhibitors, MRAs, and SGLT2 inhibitors. Equally important, these improvements were achieved while maintaining stable kidney function. Patients with CKD stage 3 or 4 had a chronic annualized eGFR slope of +0.27 mil per minute per year. For physicians, these findings matter, because they are not treating a blood pressure number in isolation.
Seeing robust and sustained blood pressure reductions alongside encouraging kidney-related measures provides the additional confidence in the potential value of TRYVIO and JERAYGO for these complex patients. Next slide, please. Edema is a known effect of endothelin receptor antagonism, and it is important to discuss it transparently. In PRECISION, edema was generally mild to moderate, peripheral in nature, responsive to diuretic therapy, and occurred predominantly during the early weeks of treatment. By approximately eight weeks, its incidence returned to levels comparable to those observed prior to randomization. Crucially, very few patients discontinued treatment because of edema. Across the entire 48-week study, fewer than 1% of patients stopped for this reason. Importantly, among the 243 patients randomized to the 12.5 mg dose and subsequently uptitrated to 25, only a single patient discontinued treatment due to edema.
Importantly, physicians are often willing to manage a predictable side effect when it accompanies meaningful and sustained blood pressure reduction in a population with high unmet need and persistently uncontrolled hypertension. With that, I would now like to hand over to Rudy, who will share firsthand perspectives from U.S. hypertension centers. Next slide.
Thank you, Amer. The clinical evidence that we just heard from Martine and Amer has provided TRYVIO a very strong foundation. What is clear, it's not more of the same. It's different. Today, I'm excited to share how TRYVIO's differentiated profile is already making a real-world impact in the U.S. for patients and physicians at some of the nation's leading hypertension centers. It's great to see how TRYVIO is delivering double-digit blood pressure reduction on top of three or more drugs with a well-tolerated safety profile and not needing any monitoring for hyperkalemia and hyponatremia. TRYVIO has no evidence, as we heard, with regards to any DDI or drug-drug interactions. This is providing physicians the confidence that TRYVIO can be added on top of any treatment regimen, this being especially relevant in a highly comorbid population.
Physicians today can prescribe the same once-daily dose of TRYVIO for all their patients down to an eGFR of 15 on top of any treatment regimen, which is a huge differentiation, as no other antihypertensive has been studied down to an eGFR of 15. The early experience that we see has strengthened our confidence in both the value of TRYVIO for patients and the commercial opportunity for Idorsia. Next slide, please. TRYVIO benefits from a broad and very differentiated label in the U.S. It is indicated for the treatment of hypertension in combination with other antihypertensive drugs to lower blood pressure in adult patients who are not adequately controlled on other drugs. Importantly, the label recognizes that lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.
This gives physicians the flexibility to identify the patients in their practices who remain uncontrolled and offer them something truly new, the first antihypertensive in decades to target a new pathway. The label highlights the unique safety attributes of TRYVIO, where no electrolyte monitoring is required. It's important for us to note that there is no evidence of hyperkalemia, hyponatremia, hypotension, muscle spasm, dizziness, and any clinically relevant DDIs, and that the eGFR remained stable. The label contains only two rows of AEs, or adverse events, including edema, which, as mentioned by Amer, was generally mild to moderate and transient. Today, together, these attributes provide a very strong foundation for physicians to evaluate TRYVIO in the context of the individual patient that's sitting in front of them. Next slide, please. What has been particularly motivating is how closely the early feedback from physicians aligns with the clinical evidence.
When we speak with specialists using TRYVIO, they tell us that they experience an effective new treatment capable of delivering each time a double-digit blood pressure reduction in patients who are already taking multiple medications. For cardiologists, this means having another pathway for patients whose blood pressure remains uncontrolled despite extensive therapy, and it is not more of the same. For nephrologists, it means being able to treat patients with low eGFR and a high risk of progressive renal damage without increasing the risk of hyperkalemia. They also value the reductions in albuminuria observed within the clinical program. Across some of the leading U.S. hypertension centers, the feedback consistently returns to the following three points. First, physicians are seeing meaningful and durable double-digit blood pressure reductions, both during night and day times.
Second, TRYVIO can be used in complex polypharmacy patients, including those with stage 3 or stage 4 chronic kidney disease. Third, physicians tell us that the treatment is well-tolerated and straightforward to use, with a once-daily 12.5 mg tablet, with or without food, and without any required monitoring. The bottom line for patients who remain uncontrolled despite their current treatment regimen, TRYVIO clearly is now a new way forward that is effective, practical, and ready to use today. Next slide, please. At the approval and wide in partnership discussions, the U.S. environment was not yet conducive to significant commercial investment. Awareness was limited, prescribing involved considerable friction, and access and distribution were still developing. We, therefore, chose a deliberate light-touch approach while continuing to work on the foundations required for future growth. We secured the removal of REMS and established a specialty pharmacy access program through Walgreens.
With its formal inclusion in the ACC/AHA hypertension guidelines in 2025, TRYVIO now has the backing that payers and clinicians look for, confirming its value for the many patients who still struggle to reach their blood pressure goals. Over the last few months, our key account managers introduced TRYVIO to the top hypertension centers and large academic medical centers. They worked closely with some of these leading specialists to help them identify and treat patients who have difficult-to-control hypertension. Most importantly, we partnered with Duke and Stanford to launch the IMPACT-HTN program, driving standardization of digital algorithms, identification of patients with the most clinical unmet need, and finally, the prospective early patient experiences on newer treatment regimens, tracking them. The market landscape is shifting rapidly. Awareness of the urgent need to treat uncontrolled hypertension is rising, and specialists are increasingly skilled at identifying appropriate patients.
Furthermore, our strategic improvements to retail availability and distribution now will ensure a seamless treatment initiation for both prescribing physicians and patients. With these important foundations now in place, the market is becoming increasingly favorable for TRYVIO. Next slide, please. The most persuasive evidence of market readiness comes from physicians who have already used TRYVIO. Several of the leading hypertension centers have gained valuable experience utilizing TRYVIO and are prescribing across multiple affiliated sites. Leading prescribers include nephrologists, cardiologists, and the top internal medicine physicians. For instance, you see the quote from a nephrologist who described the value of treating patients with an eGFR down to 15 without the concern of hyperkalemia and associated with further RAS blockade. A cardiologist reported seeing double-digit blood pressure reductions of approximately 10-15 points, including in patients already taking several other medicines.
These are, again, individual observations, but together, they show that physicians are seeing efficacy in practice, appreciate the safety profile, and are willing to prescribe TRYVIO because they recognize its clinical value. Next slide, please. When we compare where we were at approval with where we are today, the opportunity is significantly clearer. At approval, product availability was limited, market access was uncertain, specialist awareness was still developing, and our understanding of the priority patient population was largely based on clinical evidence and market research. Today, we have real-world experience from some of the leading hypertension centers, established specialty awareness, and a much clearer view of patients most likely to benefit from TRYVIO. We also have defined specialist-focused model, targeting the centers and physicians with the greatest concentration of appropriate patients.
The early introduction at leading hypertension centers has therefore validated both the differentiated clinical profile of TRYVIO and our focused commercial strategy. For patients, it clears the path to a fundamentally new treatment. For Idorsia, it confirms the opportunity to build a significant and durable U.S. franchise. Next slide, please. Our U.S. strategy, therefore, is deliberately focused on the top hypertension centers and their 300 affiliated sites, as well as leading cardiology and nephrology group practices. Together, these targets give us access to more than 5,000 priority healthcare professionals. Within these practices, we will prioritize highly identifiable patients with the greatest unmet need, including approximately 4 million patients with stage 3B or stage 4 chronic kidney disease and limited treatment options. This will leverage Idorsia's existing commercial platform to concentrate resources where they can have the greatest impact.
As a major new entrant expands awareness across the market, we can capture the momentum while focusing our investment where TRYVIO's differentiated profile makes the biggest difference. With that, I'll hand it over to Arno. Next slide.
Thank you, Rudy. Let me now walk you through the financing structure. I believe it represents an elegant solution that aligns the interests of all stakeholders. The structure and the launch of TRYVIO/JERAYGO is an important step towards the payback of the SPV notes, and at the same time provides Idorsia shareholders with an attractive direct participation in the TRYVIO/JERAYGO opportunity. Next slide, please. In total, CHF 120 million in launch funding have been committed to reach an expected break-even in 2029. CHF 72 million will come from the SPV note holders who will invest in TRYVIO/JERAYGO launch in 2027 and 2028 through new issued notes by Idorsia Investments SARL. In return, eligible note holders would receive a 12% earnout on the SPV upside value. That is 12% of the value of aprocitentan, selatogrel, and cenerimod once all debt of the SPV has been fully paid back.
These new notes would sit economically between the existing A and B notes. CHF 48 million will come from Idorsia as our contribution to the TRYVIO/JERAYGO launch over the same period. In return, Idorsia would receive a 30% share in the global TRYVIO/JERAYGO revenue and maintain 88% of the upside value in the SPV. Let me now give you more detail on these new notes. Next slide, please. The new notes of CHF 72 million would be pay-if-you-can notes issued by Idorsia Investments SARL and carry an interest rate of 6% and will mature in 2050. They would rank between the existing A1 and A2 notes and the B notes. B note holders will be offered the first opportunity to subscribe, followed by the A note holders. This is deliberate.
B note holders hold the most subordinated position, so they should also access a more senior instrument that could be attractive to them. The 12% earnout will be distributed by the SPV to three groups: the note holders who backstop the launch funding, existing note holders as a consent fee, and the buyers of the new notes. The financing is fully backstopped by a group of note holders representing a significant majority of the outstanding notes. The transaction remains subject to achieving the required note holder approvals and the completion of final documentation. We expect to launch the consent solicitation in the coming weeks. Next slide, please. Now let me walk you through how TRYVIO/JERAYGO net sales will be allocated to the stakeholders, both before and after the SPV debt is fully repaid. Note that this is a simplified illustrative example only and subject to final documentation.
Of every Swiss franc of TRYVIO/JERAYGO net sales, 3% will go to J&J under a contingent liability. 30% would go directly to Idorsia. This is an immediate revenue share that we would get. The remaining 67%, or 70% after J&J payment, would flow into the SPV, where the substantial majority of the net proceeds are distributed to the noteholders based on the existing waterfall until all notes in the SPV are paid back. Once the SPV debt has been fully repaid, the remaining value would be split 88% to Idorsia and 12% of the net proceeds to the earnout holders. To summarize, the largest portion of the aprocitentan revenue would still flow to the SPV and noteholders, as was the intention.
But at the same time, Idorsia shareholders would now also benefit from an immediate 30% revenue participation, and in addition, would benefit from the 88% of the long-term upside value of TRYVIO/JERAYGO, selatogrel, and cenerimod once the SPV debt is repaid. The interests of Idorsia shareholders and SPV noteholders are fully aligned. Both will benefit when TRYVIO/JERAYGO succeeds commercially. With this, I hand over to Roland. Next slide, please.
Thank you, Arno. As I reflect on my first four weeks at Idorsia, three things stand out to me. First, we have differentiated assets with significant unrealized value. Second, we have a clear framework for creating value through our four growth drivers. And third, we have a team that is deeply committed to realizing that potential. Over the past month, I have been impressed by the quality, engagement, and determination of our people across the organization. What matters now is execution. Next slide, please. Today's discussion highlights why our conviction in TRYVIO and JERAYGO has strengthened. Over the past four weeks, I have spent considerable time reviewing this opportunity, the assumptions behind it, and the experience gained since launch. The conclusion I have reached is straightforward. The opportunity is more compelling today than it was at launch, and our understanding of where and how to create value has become clear.
We're pursuing a disciplined fast follower strategy focused on the patients, specialists, and segments where TRYVIO's differentiation matters most. The financing proposal we have discussed today is designed to support that focused approach and accelerate the next phase of growth. While this proposal is not intended to realize the full potential of TRYVIO overnight, we believe it can establish a clear path forward, building a significant and valuable asset. Our job now is to realize its value. Thank you, and we would now be happy to take your questions.
Thank you, Roland. With that, operator, please open the lines for questions.
Yes, of course. Dear participants, as a reminder, if you wish to ask a question, please press star, one on your telephone keypad and wait for your name to be announced. To withdraw a question, please press star, one, and one again. Please stand by. We'll compile the queue in a roster. This will take a few moments. Now we're going to take our first question, and it comes from the line of Raghuram Selvaraju from H.C. Wainwright & Co. Your line is open. Please ask your question.
Thanks so much for taking my questions, and congratulations on all the recent progress. I wanted to ask if it would be possible for you to characterize a little further what you anticipate to be the primary thrust of aprocitentan commercialization. If this is going to be principally emphasizing the benefits in chronic kidney disease, the safety profile, or indeed the impact of the drug in those patients who have resistant hypertension and who are on multiple other classes of medications that would not necessarily be expected to address endothelin receptor system-mediated hypertension. Secondly, I was wondering if you could provide just a little bit more clarity on the financial aspects of the financing for the launch of aprocitentan in the United States, particularly as this pertains to the following two items.
Firstly, the extent to which the CHF 120 million in financing would cover the launch period, if this is over the first year or the first couple of years of the launch, just maybe a little bit more clarity there. Secondly, with respect to the guidance that you have provided regarding the aim to achieve break-even in 2029, if this effectively includes the commitment from Idorsia to commit to certain additional capital contribution towards the aprocitentan launch. Lastly, if you are at liberty to talk about one or two of the other drugs in your pipeline. We noted the exciting news of daridorexant being accorded breakthrough therapy, and we wanted to see if you had any comments on what the impact of that might be for the future clinical development plan in pediatric neurodevelopmental disorders. Thank you.
Yeah, thank you, Raghuram. I am happy to kick it off on the conversation front. I actually then invite Amer to quickly comment on how he, as a physician cardiologist, would look at this. I would then invite Arno to answer your question on the financial aspects, and on the QUVIVIQ pediatric side, very happy to comment at the end. The way that I look at this opportunity at the moment is that uncontrolled hypertension is a real unmet need, and it is one which, through additional efforts from new entrants, large new entrants, will only gain in prominence in a physician's mind. As physicians are looking to use new tools to better control hypertension in their patients, there will be certain patient segments where the traditional approaches do not work as well. That is where we offer a very compelling opportunity.
I see our commercial aspect coming from a high unmet need that will be further elevated in the mind of physicians, a clearly defined patient population where the need is even more pronounced, and us providing a clinical profile and a medicine that can make an immediate difference there. The fact that these patients are mostly seen in specialized hypertension centers allows us to actually have that conversation with prescribers in a very focused manner that allows us to deploy capital in a very disciplined way and start that awareness and prescription. But, Amer, if you want to, from a commercial perspective, just complement of what this would mean from clinical practice.
Absolutely. Thank you, Roland. For physicians treating resistant uncontrolled hypertension, the key aspect is a mixture of meaningful efficacy, but also high tolerability. As earlier mentioned, it is typically a silent disease, and therefore tolerability is crucial, and reduced burden of monitoring is also crucial. Therefore, we anticipate, and this has been supported by the feedback that we are getting, as Rudy presented, in real world in the U.S., that it is a mixture of all those aspects of the benefit-risk in terms of large double-digit early, rapid reductions in blood pressure, but also on top, the tolerability and safety profile that really resonates with the physicians. It is a mixture of all those aspects. Thank you, Roland.
Thank you, Amer. Arno, you want to topically go to financials?
Yeah. Thanks, Raghuram , for your questions. The CHF 120 million basically fully covers the launch funding needs, and is also fully committed. It covers basically two years, 2027, 2028, and after that, we expect to be break-even. We break even, we mean that from that time on, the assets will be cash flow positive. After that, the activity will basically fund itself.
Yeah. Lastly on QUVIVIQ, we are very excited with the breakthrough therapy designation that we have communicated today. When we presented our phase II data in pediatric insomnia, a very high unmet need, we also commented that we are very pleased with the conversations that we were having with the agencies who recognize this need, and designation today just reflects that importance and both the value of the science, I think the approach that Idorsia took to develop this medicine in this population that has no treatment options today, and obviously the impact that this can have. Amer, if you want to just comment what this means for clinical development, because it is relevant.
Absolutely. Thank you, Roland. This breakthrough designation provides an opportunity for increased enhanced engagement with the FDA, including more frequent interactions, intensive guidance, and it will really help us design the most efficient development pathway forward, which is most meaningful to patients in need. This also allows us better access to senior leadership at the FDA. This designation is focused on our development in pediatric insomnia, and any development in neurodevelopment disorders outside of this particular breakthrough designation. Our immediate focus is now to advance and optimize the phase III program in pediatric insomnia, leveraging this increased collaboration afforded by this designation. Thank you.
Thank you.
Thank you so much.
Good. Thanks, Ram. Nadia, next question?
Yes, of course. Now we'll go and take our next question. The next question comes from the line of Joris Zimmermann from Octavian. Your line is open. Please ask your question.
Great. Thank you so much for taking my questions. Two, if I may. The first one on the general scope and focus with the TRYVIO launch in the U.S. So clearly the focus is very much on that region, a lot of potential. I think that makes a lot of sense. But still, also looking at QUVIVIQ, we learned that sometimes other regions like Europe can play a significant role. Can you also elaborate a little bit on your plans, how you plan to launch JERAYGO actually in Europe and other regions? The second question is on the drug-drug interactions, which have been mentioned multiple times by both Martine and Amer. You mentioned very beneficial drug-drug interactions.
My question here will be, also considering that hypertension is often correlated with obesity, type 2 diabetes, what's the data you have, or the experience you have in terms of GLP-1s and SGLT2 inhibitors, which are very commonly prescribed drugs? Thank you.
Joris, thank you for your question. I'll take the first one, and then on the DDI part, Amer will comment. You're absolutely right. We're excited about the opportunity in the U.S., and even more so having over the last month seen the positive momentum and feedback in the top hypertension centers. That will indeed be our primary focus. But you're also correct that there is an equally high unmet need in Europe, and we are having a parallel approach in which we aim to commercialize in Europe. On the European side, directly, obviously price and value will be very important considerations. Our team is preparing those discussions, obviously building on the differentiated profile that our medicine can bring. We will take a very disciplined and staggered approach in Europe to maximize the opportunity.
Even though we didn't emphasize too much today, but obviously for the rest of the world, we also continue to have conversations with possible partners. Similarly, want to make sure that where possible, that this medicine can actually get to benefit patients. On the drug-drug interactions, Amer?
Thank you, Roland. Thank you for the question. The lack of drug-drug interactions is crucial for us to ensure that the safety and efficacy of the molecule is predictable in patients taking a large number of medications. In the PRECISION phase III study, there were a small group of patients on SGLT2 inhibitors concomitantly, around 34, 35. We saw no issues with safety in this population, and we published an abstract where there was an additional reduction in UACR in patients taking SGLT2 inhibitors. So there is the potential for additive effect and no concerns over safety for the combined use of these two molecules. We have no data so far to see the combination of aprocitentan with GLP-1 agonists, and this is something that we will look at in real-world evidence.
There's no reason that there would be any issues from a safety or efficacy perspective with the combination of these two agents. Furthermore, we've recently presented data on the consistent effects of aprocitentan in patients with type 2 diabetes and obesity in terms of reducing blood pressure and improving general markers. We also see a small improvement in certain metabolic parameters, such as triglycerides, total cholesterol, uric acid, which would fit in with the endothelin pathophysiology. So there's encouraging effects here, and we'll be very excited to see in the real world the combination use of aprocitentan, of TRYVIO and JERAYGO, with SGLT2 inhibitors and GLP-1 agonists.
Thank you, Amer.
Understood. Thank you.
Thank you so much. Now we are going to take our next question. The next question comes from Henrietta Boeg from Deutsche Bank. Your line is open. Please ask your question.
Hi, team. Thank you for the helpful presentation. Just a question on, you highlighted 4 million patients with CKD within uHTN. How many of those patients are actually reachable through the 50 centers and the 300 affiliates that you flagged in your presentation? It would also be good to know a bit about the launch plan. I guess you assume that TRYVIO is used ahead of BAXFENDY in most patients with eGFR 15 to 45, and then how do you think about the opportunity above 45? Thank you.
Yeah, thank you, Hen. On the 4 million patients, we mentioned in one of the slides that the centers we approach, we estimated about 17% of those patients would be directly accessible there. This is without us accounting for any halo effect beyond, but it also translates obviously into a very substantive number of patients that get exposed to it through this commercialization approach. On number two, I think it is an important part because what we can say is that we were able to study patients between 15 and 45 eGFR, whereas other treatments have not. Amer, if I might, how you as a physician would think about one treatment that mechanistically actually has shown no risk there and has been studied versus more rough treatment.
Thank you, Roland. In this patient population, we've seen historically with MRAs, but also now with ASIs, there is a largely an increased risk of hyperkalemia as your renal function gets worse. As renal function gets worse progressively over time, this risk further increases over time for this generally progressive disease. We were very encouraged to see a high level of safety and efficacy being retained in this population. For those patients with an eGFR above 45, we don't expect that the difficult to control hypertension population will be a winner-takes-all market. It's a heterogeneous condition, and physicians will need different therapeutic options for different patient profiles. With TRYVIO's differentiated profile, we believe this reflects the importance of targeting the endothelin pathway, which is otherwise unopposed by other existing treatments, and that this therapeutic approach will be important for many patients across the CKD spectrum.
Hen, perhaps if I just add to that, the patient profiles we have been highlighting today are the ones where the need and the differentiation is highest. But what we have seen in early experience in the U.S. is that once a center starts adopting our treatment, that there's more patients that get to benefit because it is a complementary orthogonal pathway that delivers double-digit blood pressure reductions across the whole spectrum. See this as a focused and disciplined entry point for us that allows us to have the right conversation in a focused launch approach, and yet we see that real-world experience will be carrying this medicine further.
Great. Thank you.
Thank you. Dear participants, as a reminder, if you wish to ask a question, please press star one one on your telephone keypad. Now we're going to take our next question. It comes from Sushila Hernandez from Van Lanschot Kempen. Your line is open. Please ask your question.
Hi, thank you for taking our questions. This is Sandrine on for Sushila. A little bit more about the targeted approach with targeting the 50 centers. Can you tell us anything about the size of the sales force you'll have, and how many patients do you expect to reach through every center? Maybe a little bit more context on how many patients are generally being treated at a hypertension center, and then how many of those patients are being treated with TRYVIO? Thank you.
Yeah, thanks for the question, Sushila, and I'll be handing over to Rudy in a moment to comment a little bit on the mechanics of the hypertension center in the U.S. Just upfront, we don't provide the detailed numbers of the field force, but in one of the slides you have seen that we're pointing to 5,000 prescribers, and just applying standard ratios per rep gives you an order of magnitude. It's a focused specialist field force that will be dedicated to this medicine, and we believe we'll be able to make the inroads in the hypertension centers. Rudy, if you just want to quickly double-click of what those hypertension centers mean, especially including the affiliated sites.
Thank you, Roland. It's a great question. At a big picture level, all the hypertension centers, they predominantly carry disproportionate number of uncontrolled hypertension patients. They come through that funnel into those centers. So that number is strikingly high at over 70%-80%, where you see most of their patients are coming in through who are uncontrolled and have multiple comorbid conditions. In that realm, there are also hypertension centers, pretty much again, these are diverse centers across the country. Depending on which one you look at, there are multiple, anywhere from 2- 15 outpatient sites that are linked to these hypertension centers, and many a times virtual, many a times brick and mortar. What they tend to do is channel some of these patients through those centers.
So I would really go back and say almost majority of them, over 70%-80% of the patients who come through are uncontrolled, have gone through multiple rounds of different medications, and they've tried. This is, again, an enormous opportunity, and this is exactly what we are seeing in a real-world setting, that these patients are benefiting tremendously, not only based on our efficacy and a distinct pathway, but also the tolerability profile.
Okay, clear. Thank you.
Thank you so much, Sushila. Dear participants, as a reminder, if you wish to ask a question, please press star one one on your telephone keypad. Dear speakers, we will just give a moment for our participants.
Thanks, Nadia. I think there are no further questions. So, before we conclude today's call, I would like to highlight that we will be attending several upcoming investor conferences and look forward to the opportunity to meet and speak with many of you in the coming weeks. With that, we will conclude today's call. Thank you for joining us today and for your continued interest in Idorsia. Operator, please close the lines.
This concludes today's conference call. Thank you for participating. You may now all disconnect. Have a nice day.