Good day and thank you for standing by. Welcome to Idorsia's TRYVIO Investor Q&A Webcast and Conference Call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you need to press star one one on your telephone keypad. You will hear an automated 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 now like to hand the conference over to Idorsia's Chief Executive Officer, Srishti Gupta. Please go ahead. Thank you, Nadia. Good afternoon and good morning, everyone, and welcome to our webcast to discuss TRYVIO and its role in the treatment landscape for difficult-to-control hypertension. After decades of limited progress in hypertension research, we are now entering an exciting new era, led by TRYVIO, the first innovation in hypertension in over two decades. It is the first and only hypertension therapy to target the endothelin pathway. Ahead of the European Society of Cardiology (ESC) meeting, we published an on-demand investor webcast sharing our perspectives on TRYVIO 's ability to address a significant unmet need in difficult-to-control hypertension. Since then, we've engaged with leading hypertension experts at both ESC and the American Heart Association's Hypertension Scientific Sessions. We've also met with many of you in the investor community as the back-to-school season kicks off in the US. Today, we'll address the key questions we've been hearing in those discussions and then open the lines to take your questions on TRYVIO. Joining me are Martine Clozel, our Chief Scientific Officer and a recognized leader in the endothelin system, Alessandro Maresta, Global Medical Affairs Therapeutic Area Head for Cardiovascular, Renal, and Metabolism, Michael Moye, President of IDORSIA's U.S. operations, and Julian Gander, our Chief Legal and Corporate Development Officer. Next slide, please. Before we begin the Q&A, please note that our remarks today include forward-looking statements informed by our research, physician feedback, advisory boards, and market insights. As always, we encourage you to consider both risks and opportunities when evaluating Idorsia. Next slide, please. TRYVIO in the U.S. and JERAYGO in Europe represents the first systemic hypertension treatment to target a new pathway in more than 30 years. This pathway is the endothelin pathway. That brings us to the key question investors are asking: Why is addressing the endothelin pathway such a meaningful innovation and differentiator in hypertension? Martine, can you share your perspective? Thank you, Srishti. Endothelin regulation is a central driver of hypertension. It plays a role at very early stages of hypertension, during the progression of hypertension, and at the stage of end-organ damage in hypertension. Endothelin regulation had remained unaddressed until TRYVIO. The fact that endothelin regulation was left unopposed up to TRYVIO explains why so many hypertensive patients, despite their treatment or combination of sometimes many antihypertensive drugs, could not be controlled, and their blood pressure remained higher than the target blood pressure threshold. This was particularly true for certain groups of patients whose hypertension is notoriously difficult to control: African Americans, elderly, postmenopausal women, obese patients, and those patients with CKD, type 2 diabetes, heart failure, or sleep apnea, all of which are actually associated with endothelin regulation. Endothelin probably also explains why the patients with difficult-to-control hypertension are at higher risk of death, strokes, and renal failure, almost double the risk compared to well-controlled patients. Indeed, endothelin is a multifunctional peptide. Via both its receptors, ETA and ETB, it promotes vasoconstriction, vascular and cardiac hypertrophy, fibrosis, inflammation, catecholamine release, aldosterone release, and is increased by salt, thereby mediating high blood pressure, endothelial dysfunction, and organ damage. Apositantan blocks the actions of endothelin via both its receptors and therefore is a multifaceted drug. In healthy volunteers with no underlying disease, even doses 50 times higher than the therapeutic dose of up to 600mg, TRYVIO had no effect on blood pressure. TRYVIO is only active on an upregulated endothelin system, like in hypertension. We proved this in phase two and in phase three. The lack of interference with physiology explains its very good safety and tolerability in pathology. Thank you, Martine. That's very clear. Endothelin plays a key role. It's not been tackled until now, and by targeting the endothelin system, TRYVIO is bringing a completely novel and different approach to patients with hypertension. Alessandro, let me turn to the PRECISION study. This was a registration trial with a design agreed upon with the FDA. Can you walk us through the key highlights from that study and what they mean for TRYVIO? Of course, Srishti. First of all, I would like to mention that the compelling efficacy and safety of TRYVIO is well established in labeling and further reinforced by its recent inclusion in the ACC/AHA hypertension guidelines. TRYVIO achieved a meaningful reduction in blood pressure within two weeks. This is very important in patients with resistant hypertension that are at risk of cardiovascular events. The blood pressure was sustained over 48 weeks with a decrease of 19mm of mercury by the end of the study. Talking about resistant hypertension, the design of the phase three PRECISION study was especially rigorous, with an eight-week run-in period, a standardized triple fixed dose background therapy with confirmation of compliance, and inclusion only of patients with true resistant hypertension. This trial enrolled high-risk subgroups where classical antihypertensives are least effective, including Black patients, older adults, postmenopausal women, obese patients, and those with chronic kidney disease, diabetes, heart failure, or sleep apnea, all conditions, as you heard from Martine, associated with endothelin overactivity. Looking at safety, TRYVIO was well tolerated with only two treatment-related side effects: mild early and transient edema and a modest expected decrease in hemoglobin. No drug-drug interaction was observed, a significant advantage for patients on multiple therapies like antihypertensive patients. Importantly, no signal was seen for hyperkalemia, hypotension, headaches, nor heart rate increase. Finally, the label that the FDA approved is based on the totality of the data for adults whose blood pressure remained inadequately controlled on other antihypertensives, a broader population compared to the one enrolled in PRECISION. In addition, the label includes the relevance of lowering blood pressure for reducing the fatal and non-fatal risk of cardiovascular events, especially strokes and myocardial infarctions. Alessandro, people can follow the on-demand webcast to get more details on the data for TRYVIO, but as a cardiologist, can you perhaps give us some context on the current landscape for not well-controlled hypertension? Sure, Srishti. Today's paradigm in hypertension relies on different classes of antihypertensives, those addressing the renin-angiotensin-aldosterone system, calcium channel blockers, and diuretics, which, by the way, stimulate the RAS system. If blood pressure remains uncontrolled, a mineralocorticoid receptor antagonist such as spironolactone can be added, but many patients do not tolerate it, mainly due to hyperkalemia, worsening of renal function, gynecomastia, and in addition, we observed a high discontinuation rate. Despite all the classes of antihypertensive drugs, millions of patients remain uncontrolled, and TRYVIO offers a solution with a completely new mode of action. Thank you, Alessandro. That certainly highlights the significant unmet need that a safe and effective drug like TRYVIO can address in the current landscape. What about compounds in development? Yeah, Srishti, there are several products in development, but most of them are still targeting the RAS system, including the aldosterone synthase inhibitors. These drugs are still in development, and we don't know yet what their label will look like. What we know is that their studies were not as robust as PRECISION in enrolling true resistant hypertension patients. There are safety concerns such as hyperkalemia, hyponatremia, and decrease in renal function, particularly if combined with other drugs that are targeting the RAS system. This is where TRYVIO stands apart. It addresses the endothelin pathway, a fundamental driver of disease that other treatments don't reach, with a proven efficacy and a good safety and tolerability profile. TRYVIO is differentiated to the current and potential emerging treatments. Which patient populations do you see TRYVIO being used for? If we take into consideration the new mode of action, the efficacy and safety profile, and the FDA-granted label, TRYVIO is the ideal choice for many patient groups. I can list for you some: patients with risk factors for hypertension, which will be difficult to treat because they are endothelin dependent; Black, elderly, obese patients; patients with sleep apnea, type 2 diabetes, early heart failure, and chronic kidney disease. We have patients that are not adequately controlled despite two lines of hypertensive therapies, and patients who cannot tolerate certain classes of drugs because of their side effects. There are also the patients that we have studied, so the truly resistant hypertensive patients that are not controlled despite treatment with three or more therapies at their maximal tolerated dose. I would like to tease out the patients with chronic kidney disease stage 3 and 4 and resistant hypertension, because for these patients there are currently no alternatives. In all these patients, TRYVIO represents an obvious choice with very little competition. Thank you, Alessandro. There's a large addressable population of patients with hypertension that is not adequately controlled. Michael, given that the U.S. market is central to realizing TRYVIO 's full potential, can you walk us through the key drivers that support our $5 billion peak sales estimate? Yeah, thanks, Srishti. Our forecasts are grounded in extensive market research and analytics to understand both the size of the opportunity and how physicians intend to use TRYVIO. Next slide, please. Today, of the 40 million treated patients in the U.S., there are roughly 26 million patients treated with two or more therapies, and 30%- 50% of those are inadequately controlled despite receiving treatment and therefore eligible for TRYVIO according to the FDA label, with the only contraindication being pregnancy and sensitivity to atorvastatin. This population is expected to grow given the aging demographics, higher rates of comorbidities linked to endothelin function, and increasing recognition of the severe consequences of uncontrolled hypertension. Importantly, these consequences are already reflected in the FDA indication that removes any need for a separate outcome study. We estimate that around 7 million patients, as we move to the middle of the slide, these 7 million patients are easily identifiable and are well-defined, a good area to focus on first coming into the market. Patients with endothelin-driven comorbidities often face restrictions with other therapies. Chronic kidney disease, as you've heard, is a prime example. Patients with hypertension and CKD are often treated with two or more agents, yet few effective options exist. TRYVIO is approved for patients with an EGFR as low as 15 and has demonstrated excellent safety and tolerability with no hyperkalemia and no hypotension. Other identifiable groups include patients who can't tolerate certain classes of drugs and those with true resistant hypertension. We now have real-world efficacy and safety outcomes mirroring what we saw in PRECISION. These drive adoption and penetration assumptions. As you can see, they range here from 12%- 22%. Our insights are informed by over 1,000 qualitative and quantitative interactions with multi-specialty physicians, including top hypertension centers. Physicians consistently recognize TRYVIO 's efficacy, safety, and its unique mechanism of action that addresses what additional RAS blockade cannot. In comparison with emerging therapies, TRYVIO is viewed favorably by these physicians, particularly for patients with CKD and based on the impact on both blood pressure and UHDR measures. Finally, the payers, which we know are all very important, have responded very positively, highlighting the robust primary endpoint of more than 15 mm drop from baseline, the statistical strength, and the sustained efficacy through the duration of the PRECISION study as very compelling reasons for coverage. We have set a WACC at $775 a month, and we're focused on a very favorable gross-to-net as a first-in-class differentiated therapy. TRYVIO is currently being reimbursed with reasonable utilization management criteria, which supports our commercial model. Srishti? Thank you, Michael. Beyond the U.S., we also see an additional upside from geographic expansion. Apositantan is already approved as JERAYGO in the EU and U.K., and there is significant opportunity in Japan and China. We also see that we can get further value through IP extension strategies, for example, with fixed dose combinations with the SGLT2 inhibitors and indication expansions, such as exploring renoprotective benefits in CKD. Of course, realizing the full potential of TRYVIO will depend on securing the right partner, which is why we're actively engaged in these discussions at this time. Julian, could you share a little bit more about how we're thinking about partnering discussions? Yes, happy to. Look, we've been very consistent in saying that we lead where we demonstrate scientific or commercial advantage and strategically partner where external expertise, scale, or speed adds value. Specifically on TRYVIO, partnering with TRYVIO remains a key strategic priority for us. We are actively engaged in discussions with potential partners, which reflect the interest in the asset and the opportunity TRYVIO represents. While this process takes time, we're encouraged by the progress and look forward to updating you as we move forward. In the meantime, I can tell you we continue to work very diligently and at high speed to maximize the value of TRYVIO. We've seen some of this in the past weeks and months. I think of the REMS removal, the collection of early very positive real-world experience, the inclusion of TRYVIO in the ACC/AHA hypertension guideline, and very recently the recent initiative announced with Duke and Stanford University. Thank you, Julien. Having addressed some of the key questions that we've received around TRYVIO, I think it's a good time to open the lines for additional questions. Nadia, can you please go to the next slide and open the lines, please? Yes, of course. Dear participants, as a reminder, if you wish to ask a question, please press star one one on your telephone keypad and wait for your name to be announced. To withdraw a question, please press star one and one again. To ensure everyone has the opportunity to ask a question today, please limit yourself just to two questions at a time. If you have any further questions, please re-enter the Q&A queue. Now we're going to take our first question. Just give us a moment, it comes to the line of Joris Timmerman from Octavian. Your line is open. Please ask your question. Yes, hello. Thank you for taking my question. This is Joris Zimmermann from Octavian. I have two questions. One will be on partnering that you just highlighted, Julian. Is there any timeline you could give us, or at least do you still expect to close a deal this year? The second question will be: until you have found the right partner and signed an agreement, and given the limited resources you can currently deploy in the U.S., where will you put your focus in terms of the apositantan launch? Thank you. Thank you, Joris. Julian, will you respond to the question? Yes, very happy to. Thank you, Joris. Look, I mean, you will understand that we cannot really comment on specific timelines, but what I can say, and I can ensure that the partnering apositantan is really a key priority for us. To your point, we resource this project accordingly. We, of course, want to move very quickly, also considering the time advantage we have towards emerging therapies, but you will understand that actually our focus is not only just speed, but it's also securing the right partner to maximize TRYVIO commercial success. To your second point, Idorsia indeed has limited capacities, but I think considering these constraints, we've done a lot to make sure that the product is advancing, is prepared to be launched, and the product is commercially available, and we have very good early evidence. We continue those efforts, and we are hoping to give you an update as soon as we can on achieving this goal of partnering. Thank you, Julian. Michael, maybe I'll have you add to that with your presence at the recent AHA meeting and some of the other work that we're doing on retail distribution. Yeah, thanks, Srishti, and thanks for that question. Yeah, despite the resource constraints, we are quite busy continuing our kind of launch and market prep. Srishti, as you said, we're at the major congresses, so we have a really strong presence there. We're working with a lot of the top KOLs and a lot of the top hypertension centers. You heard about the Duke-Stanford relationship that came out. We have really finalized a lot of the core materials, so we have a full digital presence. Our consumer and HCP websites are up and running. We've got print materials and things out there. The last couple of things, we're continuing our payer discussions, which continue to go really well. As Srishti made reference to at the end, the pharmacy distribution. Once the REMS was removed, we're able to move, in addition to having a specialty pharmacy, we are quite literally right now coming online with full retail distribution across all retail pharmacies in the US. Yeah, despite the resources, we're making great progress again across KOLs, congresses, payer discussions, and pharmacy distribution. Srishti? Thank you, Michael. Nadia, we'll take the next question. Dear participants, as a reminder, if you would like to ask a question, please press star one one on your telephone keypad. Dear speakers, we'll just give a moment for our participants to press star one one if they would like to ask a question. Please give us a moment. We have a follow-up question from Joris Zimmerman from Octavian. Your line is open. Please ask your question. Okay, sorry. I hope I didn't jump the line now. Two more questions. You talked about the patient populations and that you see a very broad target population, but maybe you can give us an idea based on this broader label that you got versus the study inclusion criteria. What are the kind of, where do you see the quickest uptake in the market? Which type of patients do you think will be the ones that physicians consider prescribing apositantan first? Also, maybe you could give us a little bit of an idea of the hurdles that you foresee as well. Joris, thank you for the question. Michael, would you like to walk a little bit through how we think about the targeting of the patient populations in the U.S. and how we might access them with the centers of excellence? Yeah, so when we look at that and, you know, we look at both our research and our interaction with the physicians, we're definitely seeing that the data across all the subgroups has been one of the things that's jumped out at physicians. You heard a little bit in our opening that, you know, clearly the CKD is a differentiated piece and that, you know, we see that as a great opportunity. The other thing about the subgroups that we're seeing kind of across these multiple comorbid patients, you heard about patients challenged with hypertension management, Black patients, obese patients, again, patients with CKD. The thing about the profile that continues to jump out is the fact that, you know, we have efficacy and safety across all these subgroups. We don't have any real exclusions or contraindications, and especially we don't have any drug-drug interaction problems, obviously, with these patients being on multiple medications. When we think about those different subgroups and those comorbid patients that are at more risk, including the CKD patients, we see consistently the one pill, one dose, once daily, good tolerability, no drug interactions. Those factors are what the physicians are pointing out to us that allow us to treat these high comorbid risk subgroups. Thank you, Michael. Joris, in terms of your second question, I'd like to turn it over to Alessandro. Alessandro has been attending a lot of the KOL meetings all over the United States over the last couple of months meeting physicians, understanding how they think about TRYVIO. Alessandro, can you talk a little bit about how you think about the hurdles that physicians are thinking about as they are deciding on prescribing TRYVIO? Thank you very much, Srishti. I think that, in my opinion, the best, the most important hurdle is the new mode of action. The physicians are used to the RAS system, are used to calcium channel blockers, and now they need to realize and understand that, you know, there is a new kid on the block that is an endothelin receptor antagonist, and that endothelin receptor antagonist can be very, very beneficial in the subgroup of patients that I and Michael highlighted. Basically, I see this as the major hurdle because the results are really impressive. The safety profile is also very, very good, and we have a clear understanding on which are the patients that would benefit the most from TRYVIO. Last but not least, there are many, many patients that despite they are on two, three, or even four drugs, they are still not at goal, and these patients, they need, they deserve treatment. I don't see many hurdles in front of us. Alessandro, thank you for that, and it underscores the importance for us of finding a partner who can help us on the broad outreach and the medical education required to enhance the importance of addressing the endothelin upregulation that occurs in a lot of hypertension. This is definitely something we are thinking about and focused on as we move forward. Joris, thank you for the questions again. Thank you. Dear speakers, those are all the questions for today. I would now like to hand the conference over to your speaker, Srishti Gupta, for any closing remarks. Thank you, Nadia. This concludes today's call. Thank you for joining us and for your continued interest in Idorsia. Our next scheduled update will be on October 30th when we report our third quarter results and will provide a comprehensive update on QUVIVIQ performance. Operator, you may close the line. This concludes today's conference call. Thank you for participating. You may now all disconnect. Have a nice day.