Good morning, everyone. My name is Farhan Khan, and I'm an associate with the Healthcare Investment Banking Group here at J.P. Morgan. It's my great pleasure today to be introducing Idorsia. Presenting today is Idorsia CEO Srishti Gupta. We also have key members of the leadership team: Arno Groenewoud, CFO, and Martine Clozel, who's the co-founder, chief scientific officer, and head of research, who will be joining for the Q&A panel. After the presentation, we'll have about 10 minutes for the Q&A, so please hold your questions until then, and with that, please join me in welcoming Srishti.
Hi, everyone. Thank you for joining us. I'm Dr. Srishti Gupta, the CEO of Idorsia, and it is a pleasure to be here. It's the first time I'm presenting at J.P. Morgan since becoming the CEO in July 2025. Prior to that, I was on the board. I've been on the board of Idorsia since May 2021. So today, I'll share the highlights of 2025 with you, as well as our strategy going forward for 2026. So for those of you who don't know us, we're built on a proven foundation: the talent, the legacy, and the drug discovery engine of Actelion. And that's the reason we have conviction in our strategy. The teams, the core science, and the capabilities that created so much value in the past are the same ones that will be creating value in the future.
We are executing a focused and balanced approach to our strategy, which is to commercialize our two assets as well as bring our pipeline forward in a disciplined and focused way. We're committed to creating meaningful value for our patients as well as for our shareholders. Before I begin standard disclosures, we will be making forward-looking statements, so Idorsia is unique because we have blockbuster potential products that are commercially approved, as well as a pipeline of first and best-in-class drugs, so our two commercial products, Quviviq, which is daridorexant, it's a dual orexin receptor antagonist, is poised and ready to be changing the standard of care for insomnia. We also have Tryvio or Jeraygo, which is the first approved innovation in hypertension in close to three decades. It is an endothelin receptor antagonist, and it is approved for the control of difficult-to-control hypertension.
We have a commercial footprint that extends North America and Europe, and we have a global footprint through partnerships with companies like Nxera and Simcere. On the pipeline side, our track record is proven. We have three drugs approved in the last four years. We have three additional Phase III assets, and we're in the process of starting three proof-of-concept trials. Multiple assets in our pipeline have multi-billion-dollar peak year sales potential. We're committed to creating meaningful value for our patients through changing the standard of care and how the diseases are treated. I'll start by talking about our two products, which are entering a value acceleration phase in the commercial side. Quviviq. Insomnia significantly impacts both productivity and public health. We think of insomnia as a 24-hour disease because it affects every aspect of life: how you function, how you stay safe, and how you work.
So we see a significant impact on the productivity side with over $400 billion of global annual GDP loss because of absenteeism, which is not showing up for work because of insomnia-related sleep disorders, presenteeism showing up and not being productive at work, and overall productivity loss. More importantly, what we see on the public health side is an increased risk of accidents and permanent work-related disability, as well as sleep and fatigue contributing to long-term sleep issues and health, like chronic issues like cardiovascular disease, stroke, dementia, and psychiatric and other related disorders. The biggest issue that is understated in the space of insomnia is the escalating public health crisis of mis- and inappropriate benzodiazepine use. This is where Idorsia comes in. We have brought forward a best-in-class asset with Quviviq.
It is a dual orexin receptor antagonist, and it is designed for and here for both restorative sleep and revitalized days. Quviviq is the only therapy to demonstrate an improvement in daytime functioning with statistically significant and clinically relevant patient-reported outcome that was used in the registration trial. This was a patient-reported outcome that had 14 questions across three domains: sleepiness, alertness, and cognition, as well as the mood. We saw a significant improvement in all three domains with 50 milligram use of daridorexant. Oops. While the daytime functioning is included in many labels around the world, it's not included in the U.S. label. One of our focuses this year is to do a small and focused trial to include daridorexant in the label for the U.S. Why is this important? We need to do this because we have to show that insomnia is a 24-hour disease.
We also need to prove that with physicians and patients that this is a distinction thing because there's no approved products that address the 24-hour aspect of the disease. No improved insomnia product has both nighttime as well as daytime functioning.
There's some water. Sorry.
One second. The problem right now is that insomnia is being treated inappropriately with benzodiazepines. And part of that is the U.S. healthcare system, which pushes people to products that are inappropriate for use because they're cheaper, not because they're better. And benzodiazepines happen to be cheaper. They don't have a daytime functioning claim. They don't address the daytime issues. So with a claim for daytime functioning, we would be able to show that we are differentiated and can re-access things with payers.
We've been able to build Quviviq into a global brand based on the fact that we've been able to address the issue of insomnia. And one second. We've been able to address the issue of insomnia as a daytime and nighttime disease in many countries around the world because we've been able to include it in the label. So we have shown this in Europe, where we have now changed the standard of care in many countries. And our partners in Japan, Nxera, have been able to show this with daridorexant as Quviviq in Japan, where insomnia treatments are close to 35% of the treatments for insomnia. In China, we're seeing that over 100,000 patients in the first few months of launch have become on Quviviq.
And we're well on our way in Europe because we see that in Europe, we have countries like France and Germany, which we have more than 5% or 7% of patients on Quviviq. And in France, actually, what we're seeing is that the rise in Quviviq use is coming with a drop in benzodiazepine use. We're well on looking at partnerships in LATAM, in MENA, in Israel, as well as Central Europe and other countries around the world. And the fact that we are able to create Quviviq into a global brand is a proof point that it's a best-in-class asset that has the ability to change the insomnia market. And we're able to kind of make sure that we're able to see that the blockbuster potential is there by relaunching in the U.S. So let's talk about that.
So we have the ability to change the advanced standard of care for insomnia. We've talked about Japan, where we have over 30% use. We have Europe, which is on the rise, China, which is on the rise. So what's going on in the U.S.? So we have U.S. with the idea that there's currently dissatisfied patients. We have under 2%. The market is in the DORA class. We have high use of trazodone inappropriately. We have high use of benzodiazepines inappropriately. And we have the opportunity to completely disrupt this market. So what is our clear path to global blockbuster potential with daridorexant? We have seen in Europe that as a best-in-class asset, we are driving up sales. And we have a path forward with three indications in the U.S.
As you might know, in April 2023, we filed a citizens' petition for the descheduling of the entire class, the Merck and Eisai product, as well as our product. And so what we're trying to do is make sure that we're advancing the descheduling of this asset. In addition, we're looking at new sales models. So what we've seen with the GLP-1s and other products is the direct-to-patient model. And what we're excited to do is that we're taking the same model and trying to put it forward with other assets. I think the other big thing is the daytime functioning claim. So without any other products in the space that have the ability to affect daytime functioning, we are able to bring something forward for insomnia that includes something completely distinct.
So the combination of what we see in Europe, the combination of the Europe-U.S. relaunch, and as well as expanding globally, we fully believe that Quviviq has blockbuster potential. And with U.S. exclusivity at least of 2036, we definitely have the pathway to get there. One thing that I think would be completely amiss not to talk a lot about is the fact that pediatric insomnia is a complete unmet need. And this is a staggering impact both on the patients as well as on the caregivers and families. There are no approved products for insomnia in pediatric patients in either U.S. or Canada. And the approved product in Europe is a melatonin, and with questionable efficacy. Children with neurodevelopmental disorders are even more severely impacted by insomnia. It's more chronic. It's more severe. It affects not only the children, but also affects their caregivers.
We've estimated the prevalence to be 10%-30% in the U.S. alone, and that's about 12 million patients right off the bat. Quviviq or daridorexant and Idorsia is the only company that's actually investing in a Phase II trial for pediatric investigation. So we have a Phase II dose-finding study, which is coming up in March 2026, and our trial design has included patients with not only autism spectrum disorder, but also patients with attention deficit disorder. The trial is fully recruited, and we're expecting results in Q2 2026. In addition, since we're the only one who has been pursuing this as part of our regulatory commitment, this would allow us to have some patent term extension.
I can't underestimate the impact that insomnia is having in the pediatric population, and we're excited to bring forth the first and best-in-class asset as the first mover advantage to be able to treat pediatric insomnia. Let's move on to Tryvio and Jeraygo, the first approved antihypertensive therapy targeting the endothelin system. These drugs are approved in the U.S., E.U., U.K., Switzerland, and recently Canada. What is uncontrolled hypertension? It's a major public health problem. We estimate 1.4 billion people around the world are living with hypertension, with 30%-50% of them being not well controlled. In the U.S. alone, we estimate 26 million patients not adequately controlled despite being on treatment with two or more medications, and when uncontrolled, we know that hypertension leads to a higher risk of stroke, kidney failure, heart failure, or heart attack.
Many patients will never be controlled unless you address the underlying pathology. And that pathology is often driven by endothelin. Endothelin-mediated hypertension needs to be addressed, and we have now. Well, this is the first time we have a medication that will be targeting the endothelin system for systemic hypertension. So let's talk about Tryvio and why it's uniquely placed in this landscape. Idorsia invested in a trial called Precision, and it took the hardest-to-treat patients who were truly resistant hypertension with the broadest inclusion criteria. The study was conducted in patients after they were screened on their background therapy, and then they were put on a run-in period. And both from the background therapy and after the run-in, they were checked for their hypertension, and they were still uncontrolled. So these are truly uncontrolled hypertension patients on three or more medications.
The inclusion criteria included a broad range of patients, including those with congestive heart failure, diabetes, obesity, and chronic kidney disease. So we had patients in chronic kidney disease with an eGFR down to as low as 15. This is actually a very unique thing if you're following late-stage assets in the hypertension space because other assets have not been evaluated down to an eGFR down to 15. So all patients were on three, four, or five or more medications at the time of screening. So this was a very rigorous trial. Now, what happened after that? The FDA actually gave us a label that was broader. So it's the first dual endothelin receptor antagonist approved for systemic hypertension for patients not adequately controlled on one or another medication. So even though we did the trial in definitionally resistant hypertension, the label that was received was much broader than that.
The mechanism of action, because it's unique and sort of separate from the renin-angiotensin-aldosterone system, allows for the safe addition to those other therapies. We've been approved, and we've been on the market. And because of that, we actually can see what the emerging clinical differentiation is. We see excellent efficacy and safety across all patient subgroups, including the double-digit blood pressure reduction that we saw during the trial and even better control over the longer period of time, with no increased risk of hyperkalemia, no decline in eGFR, or no orthostatic hypotension. Our approach to this has been to try to take our product to some of the top hypertension centers in order to understand which patients and which physicians are using it. But let's talk about the market opportunity.
We see a path to $5 billion peak year sales because there's at least 26 million eligible patients for the product, with 8-13 million of those patients not well controlled. We see readily identifiable patient populations, those with CKD stage three, four, those with obesity, elderly, the African-American population. All of these groups are likely to have endothelin-mediated hypertension. Using some reasonable penetration and adoption principles, we see about starting off with about 0.8-1.6 million accessible patients. And then with the WAC price of $775 and the strong payer support that we're seeing with reasonable utilization management criteria, we can see a path to $5 billion peak year sales. With geographic expansion in the countries of approval, as well as patent life extension beyond 2034, we also see the potential with expanded indications and further evidence generation.
We have excellent feedback from the market because we're already approved. We are utilizing some of the top hypertension centers, including Columbia, Cedars-Sinai, Stanford, and Duke. We see the prescriber feedback confirms the Precision results, and we have good tolerability and safety across patient groups. Our approach has been to start with these top hypertension centers, establish a medical evidence base, and then drive adoption with other physicians. The types of physicians prescribing Tryvio right now in the U.S. include cardiologists, nephrologists, and internal medicine doctors. Here's some of the feedback that we see from physicians. 10 to 15 mm drop in blood pressure, well tolerated. First-time patients have an option for patients with an eGFR down to 15, not having to worry about hyperkalemia, not having to worry about monitoring blood tests.
Resistant hypertension has its complexities, and there was a patient with a clear need, which has now normalized with Tryvio, and again, confirming the double-digit blood pressure reduction, especially in contexts where patients were not tolerating other medications. In terms of the patient populations, we actually see that we have both add-on use as well as switch. So add-on, we're seeing in truly definitional resistant hypertension. We're also seeing in those patients that are not able to take other medications, so have an eGFR down to 15, so CKD-type patients. So we see a large group of patients that these physicians are using that are add-on, and then we see a large group that are switch. So these are switching from medications that are not well tolerated that include spironolactone, clonidine, hydralazine, and switching because of the side effect profile, the dosing, or the drug-drug interactions.
So let me move on to our pipeline, which is poised to deliver the next generation of breakthrough medications. We have two late-stage assets in partnership with Viatris, which are driving part of our long-term value creation. Selatogrel for acute MI and cenerimod for systemic lupus and potentially lupus nephritis. As you might have heard in the Viatris presentation, selatogrel is poised and ready to change the standard of care for acute MI. It's a potent fast-acting and regulated P2Y12 inhibitor, which is a self-administered therapy. So upon symptoms of an MI, after having an MI, we have the ability to preserve heart muscle through the self-administration of this product. It's a phase three event-driven study that we're doing that Viatris is leading on, and they're able to enroll about over 1,000 patients a month, which is an extraordinary sort of enrollment period.
They're working very hard to make sure that their current target of 14,000 patients is met, and they're able to bring this medication forward. Cenerimod is a highly selective S1P1 receptor modulator. It's developed as a novel approach for lupus. Its enrollment is ongoing with the Phase III interim results expected for the first half at the end of this year. These are two assets that we are working on with Viatris that they're on the lead on, that we are not making any more capital investments on, but we have a royalty and milestone payment structure that would bring value to the company on our innovation. Beyond that, we have a Phase III asset called lucerostat, which has the potential to redefine the treatment of Fabry's disease.
Fabry is estimated at a $4 billion market, and it's predicted to affect 21,000 patients in key markets, which include the U.S., European 5, and Japan. It's an oral alternative to intravenous ERT, and it's mutation-independent. We started a trial about seven years ago called Modify, or actually longer ago, called Modify. It had a primary endpoint of neuropathic pain, but also a secondary endpoint on eGFR slope, as well as biomarkers for urinary and plasma GB3 levels. Unfortunately, we weren't successful on the primary endpoint, but we had very great data from the secondary endpoint and the exploratory endpoints. We decided to do an open-label extension. We published some of the results recently in Nature Communications on the interim open-label extension, and we're looking forward to presenting full results at the World Symposium for Lysosomal Diseases in February.
Again, this is a market disruptor because we can have a full mutation-independent oral alternative to Fabry's disease, and with the program that we've run with eGFR and the kidney biopsy sub-study, we have the potential for demonstrating the renal protection or the renal preservation. We also have a pipeline of first or best-in-class drugs. Outside of Lucerostat, we have three chemokines. We've mentioned those in the past. We're very lucky to have Martine Clozel here today, one of our founders and our Chief Scientific Officer, and we're happy to go through some of the mechanisms and the trial designs on those, but at a very high level, we have CCR6, which is a receptor antagonist, which we're doing a proof of concept or proof of mechanism in psoriasis, CXCR7, which is a receptor antagonist that we're using a proof of concept in progressive MS.
This compound is potentially first-in-class and best-in-class in that it has the ability potentially to both be anti-inflammatory as well as remyelinating. Then we have CXCR3, which is a receptor antagonist for vitiligo, which we'll be moving forward later this year. We're grateful to be in a financial position to drive our growth. For those of you who've seen us in the past, this might not have been an obvious conclusion from last year's presentation, but we now have cash runway into 2028. We have liquidity, or cash and near cash assets of about $258 million, and our revenue outlook is around $262 million from Quviviq sales in 2026. We're looking forward to providing full-year guidance at the end of February. 2026 is going to be a catalyst-rich year for us.
We have several areas of focus, which include continuing the sales support for Quviviq as well as new distribution models. We have the global expansion that we're continuing on Quviviq. We have the U.S. descheduling possibility in the U.S. for Quviviq for the class-wide descheduling. We're looking forward to moving forward on the partnership discussions on Tryvio and Jeraygo. We'll expand our BD efforts across our pipeline to lead where we can and partner where we should. We'll advance the lucerostat registration, as well as we'll initiate the daridorexant enabling study for the daytime functioning in the label. On the R&D milestones, we're starting CXCR7 in Q1 later in this quarter. We will report on the results from the lucerostat study. We have the pediatric readout for daridorexant in Q2 or early part of Q2.
We also have the mid-year high-dose results from the C.diff vaccine on our synthetic glycan program, as well as the initiation of CXCR3. Again, our partner Viatris will be reporting on cenerimod later this year. Again, here we are with Idorsia. It's a unique opportunity for value creation because of both the blockbuster potential products, which we're moving into a value acceleration phase, as well as our best-in-class assets, and which we are moving forward in a very disciplined way. I joined Idorsia as the CEO from the board to bring value to our patients, to the people at Idorsia, as well as to our shareholders. With the management team, we're doing exactly that right now.
And we are trying to be as balanced and focused as we can to create shareholder value, as well as set the ground for innovation going forward and really build off the revenue that we can get with our potentially blockbuster products that are on market today. Thank you very much for your time, and I will look forward to answering your questions with the management team.
Thank you so much, Srishti. Really appreciate that great presentation. So we'll kick off the Q&A session. So if you've got any questions, please feel free to raise your hand, and we'll bring a mic to you. And please hold your questions until the mic is brought.
Hi, Srishti. Thanks for the great presentation. Zainab from JPMorgan. A couple of questions from me. One was on Tryvio, just on how you're thinking about the current proportion of patients that are coming from add-on versus switch therapy, just to put that into context a little bit more. And second question is on the ASIs. I think we'll see launches from one of them at least this year. So how are you thinking about the potential impact of that on the launch trajectory for Tryvio?
Thank you for the question. I'll take the second question first. On the ASIs, actually very grateful that the ASIs are coming into the class because they'll help us define the therapeutic area of resistant hypertension. As we are a smaller company and we originally had this asset with J&J, who no longer is in cardiovascular, it's been really hard for us sometimes to demonstrate that resistant hypertension is truly a disease state and a disease area. There's a lot of people out there who believe that this is a compliance question and not necessarily a distinctive disease. And as we know, there's multiple drivers that are driving hypertension, especially when patients are on other therapies, and the endothelin system has been widely under-recognized as one of those drivers for hypertension.
We're looking forward to having some of the education on the resistant or difficult to control or not well-controlled hypertension being set by the larger companies who are coming into the space or other partners or other companies who are coming into the space. We're looking forward to differentiating ourselves, being the only drug approved right now for the endothelin component of hypertension. In terms of the other differentiations with the ASIs, I think it's a little bit of apples and oranges. If you look at the trial designs for those drugs, the inclusion criteria, as well as what type of hypertension they were treating, they were not necessarily designed to treat truly resistant hypertension.
There was a component of resistant hypertension as well as uncontrolled hypertension in their trial designs, and their inclusion criteria didn't go down beyond a 45 eGFR, at least in their registration trials. So we have a truly distinct value proposition in that our inclusion criteria are much broader than that, and the mechanism of action is very different. In terms of the patients, on your first question on where we see the most patients or how we're seeing the distribution of patients between add-on and switch, I think it's a little bit early for us to tell, but I think that we do see the switch patients are definitely ones where the distinct value proposition is very clear because they are not tolerating or they're not effective on the blood pressure medications they're on.
And given the high concerns around polypharmacy and drug-drug interactions, we see that physicians are very excited to kind of be able to move patients off of drugs where they're not effective into a drug that's immediately, almost immediately recognized as effective in them. And then in add-on, we do see it most first and foremost in definitional resistant hypertension because that's where the trial is most unique. Martine, do you have anything to add on the patient populations?
On the patient populations, there will be care to take for prescription of ASI. Combination with MRA will not be probably possible. Potassium will have to be taken into account, the level of kidney function at baseline where we have a very broad possibility to use without the need to control for much, except pregnancy perhaps, but otherwise there is really no need for controlling before and during treatment. There is no need for blood control, no risk of hyperkalemia, no risk of degradation of kidney function, no hyponatremia.
We're looking forward to continuing real-world evidence, though, to be able to more clearly understand what the ratios are going to be between add-on and switch. Our guidelines are open to either one of them, and the label is open right now because it's on one or another medication, but as we get more and more real-world evidence with use, we're looking forward to clarifying this and then really targeting our efforts.
People who have been trying, I think, three medications or more and have not been, despite compliance, able to improve their blood pressure are likely to have an endothelin-dependent hypertension.
Srishti, I've got a question for you. Just wanted to say, obviously, congratulations on the growth and momentum of Quviviq. Could you help us better understand what is kind of unique about the design of Quviviq?
Martine, maybe I'll hand that one to you. Some of the properties that make Quviviq the best-in-class.
Yes, thank you for the question. Quviviq is a result of many, many years of work to optimize a molecule to have a duration of action which would not be beyond this duration desired of sleep. So the result of the compound is that we are improving by one hour per night sleep duration in patients who are either having difficulties to fall asleep or patients who have waking up in the second half of the night. And the effect of Quviviq is on both. 30 minutes improvement of time to fall asleep and 30 minutes shortening of the awakenings. What is quite incredible is that because of the pharmacokinetic and pharmacodynamic properties of the molecule, which works during the totality of seven or eight hours of night, the morning is not associated with any carryover somnolence effect.
On the contrary, we have a dose-dependent improvement in alertness in the morning. And because of this profile, we have been able to see that we could potentially improve what is one of the biggest problems of insomnia and chronic insomnia in particular, which is daytime functioning impairment. So we developed and validated a tool which is the IDSIQ, this PRO, where the patients are asked on 14 questions every evening, and these questions have been optimized with insomnia patients, so they are highly relevant. And we have seen that thanks to the profile, improved quantity and improved quality of sleep, no carryover effect. We have been able to improve this daytime functioning rapidly, but increasing even in efficacy over time, and that's completely unique.
Thank you, Martine. Okay, I've just got one more question I wanted to bring up. You mentioned the synthetic glycan vaccine platform, so can you just share a bit more details on that?
Martine, do you want to take that one?
So we had been, at the time of Actelion, asked to try to create a new core with another approach to the research we have been doing on small molecules organic chemistry. And we decided, after reviewing many, many different technologies, to create these synthetic glycan chemistry-based vaccines. And we have started working. We have published a few papers on different bacterial approaches, and we have decided to go first with Clostridium difficile, which is one of the very prevalent CDC-cited priorities. And this synthetic chemistry allows to make in a lab enough for millions of doses and to be able to have a highly reproducible vaccine. But in addition to that, it doesn't require growth of the culture of the bacteria. And Clostridium difficile, for example, is an anaerobic bacteria, which is impossible to grow.
This synthetic chemistry allows to mimic a glycan, which in the Clostridium difficile situation is a natural glycan, and we have, therefore, for the very first time ever, the possibility to target not the toxin, which are easy to target, but the bacteria and the spores, and we have obtained a proof of concept, which I think is very important for the C. diff development, but also as a proof of concept for our technology beyond the Clostridium difficile. The results are showing that we have immunogenicity only after two injections already in a dose-dependent fashion, and that these antibodies, which are developed, are functional, recognize the bacteria and are functional. Behind that, we have a portfolio of vaccines, Klebsiella pneumoniae, so we are really basically targeting the MDRs, the bacteria which have a high likelihood of multi-bacterial resistance, multi-antibiotic resistance.
For the Klebsiella vaccine, for example, so we have a lot of derivations from that research. We have the possibility to create new hybrids, for example, or artificial glycans, which will cover several of the natural glycans of the surface of the bacteria, and that's what we are applying for Klebsiella. Behind that, we have gonorrhea, and we are working also on additional technologies which are very promising.
Awesome. Thank you.
Awesome questions.
Another question there?
I have one other question, which was on the SLE readout. I think you said one of the Phase IIIs might be this year. So just on the, I think you said it's an S1P mechanism, so just trying to understand because there's been a lot of developments in SLE, like BAFF receptor, CD40. So thinking about what we should expect to see there from you in the Phase III and why S1P might be a better target than some of the other mechanisms that are being explored.
We have our partners, Viatris, in the room today, but Martine, I think you were pivotal in sort of designing the Phase III program. Do you want to talk a little bit about that?
Your question was on the mechanism or on the Phase III ?
The readout.
The mechanism and also what we see and what we expect to see in the Phase III, why the mechanism might be better.
The mechanism is very, very interesting. It's very broad. Zainab is able to target basically a combination of what all other approaches are doing. And therefore, the results have been very promising for now. And Viatris is now in two Phase III trials. In systemic lupus and lupus nephritis, I believe.
The Viatris presentation yesterday had a very thorough sort of on that one. And we appreciate that Viatris has this scale and the ability to move this one forward, moving this innovation forward to patients. So they're right in front of you. You can grab them.
Do we have time for?
Any other questions? Thank you for the time, everyone. We're looking forward to keeping you posted on Idorsia's progress and hopefully we may be back next week.