We're online. Is there an online? No. Now we're on. OK, thank you, guys, for being here. Super excited to have Srishti join us from Idorsia. I'll let you kick things off and maybe introduce the company over the next 20 minutes.
Hi, everyone. Thanks for joining. I'm Srishti. As you can tell from my accent, I'm an American. But Idorsia is a Swiss company. It was founded in 2017. It was founded when J&J acquired Actelion, which many of you may know. The founders of the company had one request, which was to take the R&D pipeline and many of the people who were not moving over to J&J for the PAH portfolio to start a new company. And that company was Idorsia. So Idorsia is a relatively new company, 2017, but has a pipeline that actually dates back to 1997 when Actelion was formed. And a lot of the research teams that we work with right now have been together and worked together for decades. And so the pipeline is very robust. We have a lot of skills and legacy with our R&D team.
And we have a lot of success. Actually, we've had three approved products since our founding. So Clazosentan, which is approved in Asia for subarachnoid hemorrhage. Daridorexant, which is approved as QUVIVIQ, which is used for the treatment of insomnia disorder, which is now used in 13 countries. And I'd love to chat a little bit more about that. And Aprocitentan, which is an endothelin receptor antagonist, which is approved for resistant hypertension. And it's approved in the U.S. as Tryvio and in Europe as Jeraygo. And we have three actually phase three assets, two of which sit in a partnership with Viatris and one which is the Lucerastat for Fabry. It's an oral substrate reduction therapy. So the pipeline has been very robust. We have commercial assets. And we've been building out our commercial presence in Europe. And we have a commercial presence in the U.S.
Outstanding. OK, excellent. So maybe just to kick things off, I know you guys have a product on the market now doing decent sales. Maybe let's start there and we can pick up the conversation there.
Perfect. So that's QUVIVIQ . QUVIVIQ is a dual orexin receptor antagonist. It is an extremely well-designed product. And even though it was not the first in class in the DORAs, it's probably known as the best in class because of its design. The founders actually synthesized, not screened, but synthesized 25,000 compounds or versions of it before they landed on Daridorexant. And one of the things that they were looking for is sort of the optimal PK. And so one of the features of it, which is something that translates to clinical use, is that 80% of it is cleared within eight hours. So that really means that the next day there's no grogginess. And the sleep onset is very rapid. And so the sleep architecture, as it's looked at through the trial and it's in the follow-on trials, is very clean.
When patients and prescribers are using this product, it tends to stand out among the other DORAs because of its profile.
Do we know that equivalent number for Suvorexant and some of the other programs?
Yeah, so Suvorexant is a product that is a Merck's product. It has a different approved dose. And actually, the approved dose is not the dose that is the most effective dose. It actually has to be increased over time. And then lemborexant, which is the approved product from Eisai, has a different PK. And one of the features that patients have reported back is that it lasts a lot longer. And so there is a little bit more of a grogginess.
Also in the morning, there's probably.
Yeah, there's morning grogginess. So that's a little bit of the.
How's the NBRX looking then between the three since you've been on the market?
So we've been on the market since 2023. And when we were heavily detailing, and I'll go through a little bit of why we're not heavily detailing right now, we were the NBRX leader. So when there was both detailing with reps as well as a pretty aggressive campaign and promotional campaign, we were an NBRX leader preferred among many patients because of this profile. And we actually see this, as I mentioned, we're launched in 13 countries around the world. In Europe, very good sales. And patients are reporting strong usage. In Canada, there's both Lemborexant as well as QUVIVIQ . So Dayvigo and QUVIVIQ are available. And we see the QUVIVIQ preference. And in China now, we just launched a few weeks ago with our partner Simcere. They launched it.
Eisai's product, Lemborexant, Dayvigo is also available and seeing a lot of preference for QUVIVIQ based on the profile.
Got it. So can you maybe remind us about some of the history? I'm not familiar. So 2023 is when it launched. So presumably, promotional spend was heavy in 2024. And then it kind of started to pull back in?
Yeah, it started to decline. I think some of the challenges that we faced with QUVIVIQ in the U.S. is that it's very sensitive to detailing and requires a lot of effort in terms of a sales force. We're a Swiss company that had only one commercial asset at the time. And so coming in and negotiating payer positions was quite difficult for us, also as the third to market in the DORA class. Unfortunately, also, the commercial insurers tend to steer to other products in the space that are not DORAs, for example, trazodone and benzodiazepines, just because they're cheaper and they're genericized. And so patients are being asked to go via potentially addictive substances in order to get access to a dual orexin receptor antagonist. And then because we were later to the market, Merck actually was out there since 2016 or so.
2019, something like that.
Yeah, something like 2014, 2016. We weren't able to find the same payer position. So if Belsomra has better sales, for example, in Medicare patients or with CMS, it's because it was first to kind of negotiate those positions, which didn't move. So it's been challenging. It was challenging on that front. I think the other thing that we underestimated was the impact of it being a Schedule IV product post the opioid public health crisis in the U.S. And I think that one of the things that happened out of that is that both prescribers as well as pharmacies were more strictly monitored for the number of scripts and the number and how they were dispensing products, the Schedule IV products. And so that impacted as a launch product, I think that impacted us quite a bit.
Got it. So when was the promotional spend pulled back? 2024?
Over the end of 2024 into 2025, so now we're using a model where we're really focusing on having our most loyal patients and prescriber base, and we're using a much more limited omnichannel sort of e-detailing model that we're using with 20 reps that are mostly doing digital promotion, and we've maintained our sales, and we've improved incredibly our paid prescriptions, so our revenues have stabilized, and we do find new prescribers with this model, and partly, this is not the model that we are saying is our model to go forward, but it's really our model that we're using at the moment as we're waiting for a descheduling decision.
Oh, when is that?
I wish I knew. It is definitely one of those things that doesn't have a statutory framework, unfortunately. There's two parts to the process for descheduling. One is that the FDA does an eight-factor analysis. It goes through an HHS clearance process. Then it gets forwarded to the DEA. The DEA does an evaluation of the recommendation from the FDA and posts it for public comment. When we realized that the DORA class, because the precursor products from Merck and Eisai were also Schedule IV, that we would also be scheduled, we actually applied soon after our approval for a class-wide descheduling. That.
Are they still Schedule IV?
Yeah, they're still Schedule IV. So we have.
And they never tried?
I mean, even though we're the smallest of those, we led the charge on sort of doing the class-wide descheduling. And we felt that the class, unfortunately, was getting sort of caught up in being in the hypnotic class for the FDA, even though the pathway and the orexin is quite different.
So not having the schedule would do what practically from a patient experience perspective?
I think a lot of things, so one is that hopefully we would be able to educate physicians, and then it would open up the prescriber base. I think the second bigger thing for us is that it would open up the ability for patients to be able to get it at retail pharmacies. Often, retail pharmacies don't carry it because of the Schedule IV, and then the last big one, which is the one I'm most excited about, is that we've seen a lot of the new models of distribution, end-to-end distribution, and even prescribing and distribution to patients that we see that in China, actually, with telehealth prescribers and online pharmacies, and without the schedule, we could open up online pharmacy access to patients, which we can't do right now.
Got it. OK. OK, so I didn't realize there was this big holdup. So it could be at any point, presumably.
Yeah, and I think we're talking about the order of months, not years, at this point, because we have been at the years point now.
Is there a back and forth? OK, well, I guess we can go at it more systematically. Is the FDA analysis complete?
As far as we understand, the FDA analysis is completed, and it's in the HHS clearance process.
OK, and then it'll get to DEA.
Then it'll get to DEA.
And then public comments, and then presumably.
Yes, and we're poised and ready for the public comment period. We have a range of supporters from first responders to health care workers. The NIDA has reported that the DORA class is one of the top 10 classes of drugs that are being used right now for the evaluation of medications that could be used to treat substance abuse disorder. I mean, one of the reasons it's classed is it's classed because of potential abuse. It's actually being viewed by NIDA as a potential product that could treat substance abuse. So it's quite the opposite of, I think, where the perception is. When we do an FDA Adverse Event Reporting System analysis, and based on our conversations with other government agencies like the DOD that's using the product in PTSD, we find the product extremely safe and non-dependent.
We see that in the FAERS database, which was a data poster that we had at World Sleep.
Got it. This descheduling will be not at Idorsia specifically for the class?
It's a class-wide. We're working with Eisai on a class-wide.
OK. And I guess the next point is, when is Merck genericization for their Suvorexant?
Their loss of exclusivity, I think, is in the end of 2029. As for whether or not generics will enter, it's hard to know when.
Are there INDs filed?
Not that I know of. I don't think so.
No one even attempted it?
I mean, unfortunately, it's a product that because of its circumstances, it's low. I mean, of the total Rx for insomnia in the U.S., DORAs in total are less than 2%. Because we're a system that is very much focused on trazodone and benzodiazepines. In contrast, if you look at Japan, DORAs as a class are 30% of insomnia treatments. And so that's a context in which we see that the value of a non-addictive effect for the wake signal, for the suppression of the wake signal pathway, is seen as the most effective. In countries in Europe where we've launched now, in France and Germany, for example, we're close to 5% of total Rxs for insomnia. So in both those countries, we have reimbursement from the government. We do the detailing through our own reps, the specialties in neurology and psychiatry.
And then we do partnerships with companies like Menarini, who have great relationships with GPs. So I mean, when the country context is right and the insurance coverage is there, you can really see a shift in the standard of care.
I have to ask, because you guys spent so much time on the orexin antagonist side, was there ever any effort done on the orexin agonist side?
We've had an orexin agonist in our portfolio since, I think, the 1990s. And it's actually the mirror image. It's designed to be the mirror image of daridorexant. So in terms of its PK, we're very excited about it. Even though there's a lot of activity in the space, we do feel like it has a lot of features from our modeling work on where it could be really distinctive in terms of its being best in class. So we are working on figuring out ways to get it into humans and to continue to accelerate its development. And so we're very excited about it. And we.
Is that approaching phase one? Is that where it stands?
Yeah, it's approaching phase one.
OK, but it's an active program.
It's an active program. We are definitely very much more excited about it, and for us to be able to tackle both ends of both orexin antagonism and orexin agonism would be very much something that we would love to do, given our long-time commitment to the orexin space.
OK, great. Any questions before we move on?
In Europe, so you say countries and you're adding new countries. And then there's dynamics within the country. So can you talk a little bit more? Because right now, the story is Europe growth for QUVIVIQ. Can you give us a little bit more detail there?
Yeah, thank you for the question. We're growing. We guided towards CHF 130 million this year in 2025. And in our nine-month earnings, we're on target for that. We're thinking around that's double from last year. So we've more than doubled our revenue by just our European program. We're guiding towards around CHF 210 million and CHF 270 million in revenues over the next two years. So we're looking towards that as our outlook on this. And a lot of that is based on working through reimbursement as sort of the first thing. In many of the countries in which we have affiliates, we're still working to establish the reimbursement with the national authorities. And then once we have the reimbursement, we're expanding the co-promote. One of the things that we've done a lot in Europe is broadening the prescriber base.
And that is through our medical affairs work, both with phase 4 and investigator-initiated studies. So we have a lot of ongoing work right now on the use of QUVIVIQ in patients with concomitant psychiatric disorders, with anxiety, with neurological disorders like restless leg syndrome. We have a great program on looking at insomnia and menopause. And we are looking at substance abuse disorder and smoking cessation. We have some work on sleep apnea. So we have the broad label that says that this is for use for any patients with chronic insomnia disorder. But as we strengthen the evidence base and physician comfort on using QUVIVIQ in polypharmacy settings with patients with other complications and comorbidities, we're finding that even within countries, we're able to deepen the prescriber base. And that's an important thing for us as we think about the growth. So reimbursement's key.
Broadening the prescriber base through this medical evidence is also key, and then co-promoting to the GPs, because this is largely a big access point from the general practitioners.
Got it. I have to ask, on the two partner programs with Mylan and Viatris, which are phase three readouts late next year, early 2027, what are the economics with Idorsia still? And do you guys have a higher conviction on one program over another?
We're very, very excited about both the programs. I think Selatogrel is a completely innovative both compound as well as a design. It's a self-injector with a platelet inhibitor that would be used in a situation where a patient has symptoms of a secondary cardiac event. And we're very grateful that we were able to partner this with Viatris, because the scale of this trial and the event rate can be low enough that you actually have to screen quite a lot. You have to have a lot of patients in the trial in order for you to be able to show the prevention of the serious cardiac events and the deaths. So we're very excited about that. That one has been something that I think we have had a long-time excitement on. And then the Lupus program as well is a pretty large-scale program.
So I think across therapeutic areas, we think that both programs are enrolling super well. They're on target for that and the readouts. And in terms of the economics, we have milestones and royalties associated with both of those programs.
Got it. OK, great. And then Cenerimod, similar economics on that one?
Similar economics. I think we only have a couple of minutes left. But we would be amiss not to talk about Aprocitentan, our product for resistant hypertension.
I was certainly heading in that direction. So let's expand on that.
OK. So our founders, Jean-Paul and Martine Clozel, have been working in the endothelin space since the '80s. And as you know, their success in Actelion came from pulmonary arterial hypertension, where they worked up Opsumit and Tracleer for use in PAH. I think they always had this idea that the systemic hypertension could also be addressed. And then actually, there are some patients who will not come to goal for their hypertension without addressing the endothelin-mediated hypertension. And so Aprocitentan was the result of their work on designing a product for systemic hypertension. It's an under-recognized pathway. I think most of the assets that are out there right now are on the renin, angiotensin, aldosterone system. So it's a different pathway. I mean, I went to med school. It's not one that we learn a ton about.
But it is the first innovation in hypertension in close to three decades.
Right. And the status of this program, I think it'll be a surprise to people who learned this is an approved product.
This is an approved product. It's medically available.
But not launched.
It's introduced, but not launched. And so we've had limited ability to launch it. And we've been looking for. We actually had this product in partnership with J&J. And then J&J made the strategic decision to withdraw from two therapeutic areas. One was infectious disease, as many people may remember. And the other one was cardiovascular. And that was around the time that we realized that they did not want to take Aprocitentan forward. But because of our history with it, we decided that we would buy the rights back for it. And then we would try to get it to the launch point.
And I guess from your perspective, what's the priority now? A big pharma partner? Or are you even open to because there are several small biotechs that are approaching commercialization as well in the blood pressure?
I think we're very, very open. I think one thing that's become very, very clear is that while we did a PRECISION trial that was very, very clinically designed around resistant hypertension, the label that we received from the FDA was broad, so it's for hypertension that's not adequately controlled on one or another product. And then what's become even more clear over the last few months, as other products have come to data, including AZ and Mineralys products, Baxdrostat and Lorundrostat, is that our product has a clear differentiation in renal. So the inclusion criteria for PRECISION has eGFR down to 15. Also, there was no discontinuation for adverse events. And then there were no adverse event signals for hyperkalemia and hyponatremia or orthostatic hypotension.
And so those are actually signals that we see in some of the other products with only an eGFR cutoff of 45 in their registration trials or phase three trials. And then their follow-on trials in CKD are only going down to 30 eGFR. So we have a very distinctive renal safety profile. And so I was just at ASN a couple of weeks ago. I think you were there too. And nephrologists definitely see a clear usage of this product where they don't have to monitor patients for hyperkalemia. So as you talk about sort of getting this product to patients, we definitely see a circumscribed patient population where Tryvio's value is most obvious. And a way to get to those patients through hypertension centers of excellence, large nephrology practices that have more than 50 nephrologists in them, large cardiology practices. So we're open on the partnership strategy.
We're just incredibly motivated right now to ensure that we can get this product to patients as soon as possible.
Where's the REMS app for this program?
So the REMS was removed in late March 2025.
OK, so no more REMS.
So no more REMS. After 20 years of experience with the endothelin receptor antagonist, the FDA decided to remove the REMS for this product. It was a very limited REMS. It was a one-time registration for prescribers and physicians. They kept the black box so all ERAs contained the black box warning around EFT, embryo-fetal toxicity. But the REMS was removed. So there's no mitigation strategy and no necessary kind of steps to be taken. So that actually happened after our partnership.
My last one is the pricing established on this? Or would the partner get it?
Yeah, the WAC price has been established at $775 per month.
OK, got it. Excellent. Fantastic. Maybe just as we wrap up, I was going to hit up on your CCR6 and the CXCR3. What are the timings on that for getting any clinical data?
So we've started our CCR6 proof of concept study, which we're doing in psoriasis. So even though there's a range of diseases that are T helper 17-mediated, inflammatory, and autoimmune, but we picked psoriasis as the one for the proof of concept because it has a very clean TH17 mediation, as well as the fact that the PASI is a clean proof of concept test. We had a 12-week duration. It was something that we could do our fastest possible POC on. As other indications, we could have chosen like atopic dermatitis. Those are a little bit more heterogeneous in their presentation for TH17. So we decided to go with something that was very clean for the POC. CXCR3, we're working up for vitiligo. It's sort of a similar test for proof of concept to the PASI. It's called the VASI. And that.
Oh, I don't know that one. VASI?
VASI. It's vitiligo area severity index. So that's what PASI, so.
Study just came up with it.
No, it's an established one. And then we are starting that one in the first half of 2026.
Fantastic, fantastic. It sounds like there's a lot of clinical events that are coming up.
Yeah, the biggest one, I think, is our phase two for pediatric daridorexant, so huge unmet need in pediatric insomnia, so still life cycle for QUVIVIQ. I think we would love to be able to meet the pediatric unmet need in insomnia, so in March, end of Q1, early Q2 of 2026, we'll have the readout on our dosing study for the pediatric usage of daridorexant.
Got it.
And actually, one of the things that we tried to do because of the EU requirement is that we included patients that have diagnoses of being on the autism spectrum as well as ADHD. So we are trying to show insomnia in patients and then also in those other areas, because we think that there's a higher incidence and complications of insomnia, both for those children as well as for their families. So being able to address it in these special populations would be something that would be really high value.
Excellent. I know we're at time. So thank you so much for making time.
Thank you for having me. It was great.