All righty. Hi, everyone. Thank you for joining us in the room and online at TD Cowen's 46th Annual Healthcare Conference. I'm Joseph Thome, one of the senior biotech analysts here on the team at TD Cowen. It is my pleasure to have with me today the team from Idorsia, and we have CEO Srishti Gupta, who's gonna give us a brief overview, and then we're gonna dive into some of the programs. Maybe just to kick things off, before we get into sort of the specific Q&A, the company has done a lot over the past kind of year and a half to focus and maybe just give us a high level as to where the company stands now and what should investors be looking for, and then we'll kinda dive into the specific programs.
Thanks, Joe. Thanks, everyone. It's great to be here. Idorsia is a unique company because we have commercial stage assets, Quviviq, which is a dual orexin receptor antagonist, and Tryvio, which is an endothelin receptor antagonist for systemic hypertension, as well as a pipeline that has been built on the legacy of Actelion, and actually dates back to the 90's and is a proven foundational pipeline of drug discovery engine. As you said, you know, the last year has been busy for us as we've really tried to align our financial position with our revenue position and understand how we can unlock value from our commercial assets, as well as continue with the growth-forward pipeline sort of in a focused way and think about how we're moving forward in the pipeline.
We had a debt situation last year in January 2025, which we've now restructured, leaving an unencumbered equity story for Idorsia that's really built on the foundation of Quviviq and sales that we have seen actually quite contrary to how global sales tend to work, is we've done amazing..ly well in Europe and Canada, and we can talk a little bit about the U.S.. A pipeline which is amazing, and I think we recently released some of our data and our pathway forward on lucerastat for Fabry disease, as well as we have, you know, three chemokine programs that have started or are in the process of starting. We're very, very excited about that, and excited that we have the opportunity to start telling our equity story again, and happy to dive into the pieces of that.
Great. Maybe we'll start with Quviviq. Obviously, the company just reported some pretty solid, 2025 sales, as you indicated, seeing some pretty strong ex-U.S. growth. Can you kinda tell us where geographically maybe you're seeing the most interest in Quviviq? And it seems like the uptake trends in Japan in particular are also really interesting. So kinda how much growth is left in these regions, and where are you seeing the most interest?
Yeah. I think two areas. As you noted, we out-licensed, and as part of the sale of our Asia-Pacific business to Nxera. Nxera with their commercial partner, Shionogi, have been doing an excellent job with Quviviq in Japan. It's fascinating that when the context is right, the power the DORA class has to treat insomnia. Maybe just a second on insomnia before we dive into the commercial. This is not the nighttime symptoms, like the sleep onset that's most important to people. It's really the next day. How do you think about functioning? How do you think about your alertness, your cognition, your ability to manage the demands of a workday, a family day? Especially in elderly people, how do you think about that without having sedation and grogginess?
For us, Quviviq is an amazing product because it's really designed to be optimized for the sleep-wake cycle, and it suppresses a wake signal as opposed to causing sedation, and 80% of it is cleared in eight hours. In that context, the Japanese have really recognized, the physicians have recognized the value of it, and in Japan, the DORA class is around 37% of the total insomnia market. We're seeing interesting growth right now in China with the partner Simcere. They have 300,000-400,000 patients on Quviviq in the first six months since the launch, and we are working to make sure that we can get Quviviq to patients in a lot of other geographies. Most recently, we announced LATAM.
The place that we commercialize Quviviq, where we're really seeing, a strong uptake based on a very focused commercial model, is Europe and Canada. In Europe and Canada, the model is to focus first on reimbursement, because that's a big driver of use. We do very focused promotional efforts with neurologists and psychiatrists, then we look for co-promotion partners for the GP population. We're seeing a ton of traction there. I think I guided to around CHF 134 million sales in 2025. CHF 130, we actually outperformed with CHF 134 million Swiss franc sales, and our outlook for 2026 is around CHF 200 million.
The company recently indicated a potential expansion maybe to primary care for prescribing. I guess, can you talk a little bit about the current prescriber base in the regions that you're seeing some pretty good adoption and how you can maybe penetrate that better with some alterations to the sales force?
Perfect. It's a great question because I think that you establish the medical value with the specialist focus with neurologists and psychiatrists, and you really sort of help them understand how to use it in difficult patients that have polypharmacy issues or comorbid anxiety, comorbid depression, or elderly patients. The volume of patients and sort of the magnitude of the problem for insomnia with around 10%-20% of people suffering from sleep onset or sleep maintenance issues is really from the GP population. Once GPs see either initiations from neurologists and psychiatrists or see the medical value established with a specialist, they're more comfortable to then prescribe.
In countries like France, Germany, and now recently in the U.K., we're working with Menarini, in Europe, who has years of established relationships with the GPs in order to co-promote, and make sure Quviviq is available to physicians there. A bulk of the prescriptions come from the GP populations, but it's the combination of unlocking the reimbursement and then establishing the medical value with the specialist community, and then finally, making sure that there is a co-promotion partner who can help us access the broad base of prescribers.
Great. Maybe shifting over to the U.S. opportunity. Obviously, the scheduling has, you know, provided an impact in the U.S.. Can you kind of walk us through, you know, why is the current scheduling environment as it is with the DORA class in the U.S., and maybe what are some potential avenues to lessen that for Quviviq in particular?
So, Daridorexant or Quviviq is the third dual orexin receptor antagonist to be approved by the FDA. The first was Merck's product, and the second was Eisai's product. At the time of Merck's approval, I think it was in 2016, they were given the schedule. It wasn't based off any preclinical animal sort of signals. It was really based off something that the FDA used, which is called the human abuse potential test. Which is kind of a little bit of a wonky test, and, you know, we've kind of had people who've published on whether or not it actually is predictive of future drug liking or future abuse potential.
It's often said that for new classes of drugs like the dual orexins, it actually is discrepant from, like, the actual real world data. Unfortunately, after Merck's approval, Eisai's product was approved and still carried the schedule because there was very limited availability and limited real world kind of evidence to back up the fact that the discrepancy was there. We were approved, and at the time of the approval, now there was some significant more usage in the U.S., and we tried to talk to the FDA about revising the schedule. They had recommended to us at the time that we should actually go for a Citizen Petition. In April 2023, we went for a Citizen Petition that was class-wide.
Recently we were reflecting on where we are and it's been surprising actually when we did the sort of analysis of it. We probably have around 13 million patients outside the U.S. now who are on DORAs between extensive use in Japan, China, Canada, and Europe. In some of those contexts, we're the only DORA. We want to go back to the FDA and say, in addition to not seeing any signal for abuse dependency or withdrawal in the FDA's own adverse event reporting system, we have six or seven x usage outside the U.S. where the DORAs have never been subject to CSA-like controls, and we see consistently no signals for abuse, withdrawal, and dependency.
We're hoping that the combination of the idea now that we can really show that the human abuse potential test is discrepant with this total body of global data that we're able to move on the descheduling.
Perfect. Maybe even in addition to that, you're going to see some pediatric data soon from the therapy. I guess, what are you looking to see in that readout, and would that be almost another avenue? It feels like if you know, if it's safe in pediatric populations, it should help overall descheduling as well.
Yeah. Pediatric insomnia is a critical and high unmet need or sleep disorders, and for sleep onset and sleep maintenance. We see the severity of insomnia even more so in patients that carry NDD diagnoses or ASD or ADHD. The impact not only on the children, but also on the providers is quite significant. As part of our pediatric commitment to the FDA and to PDCO in Europe, we decided to pursue a pre-pediatric program. What we're reading out at the end of Q1 or early Q2 is our phase 2 dose-finding study.
When we designed act of, you know, of treating insomnia in these patients. In terms of what we're looking for, we have three doses. So we'll do a dose, you know, there's a dose range study, but we're also looking for the endpoints on sleep, as well as an exploratory endpoint in terms of a patient-reported outcome on, from the parents as well as the children on their sleepiness the next day. This is actually very important to us because that's a key distinguishing feature of our, of daridorexant in the adult population with Quviviq is the daytime functioning.
We have data that from our registration trial that shows that there's improvements in sleepiness, alertness, cognition, and mood from long-term use of Quviviq. If we could show similar cognition alertness in children not only by treating their sleep, but just in terms of the orexin, it would be an amazing thing, especially in these patient populations that carry these diagnoses. To your point around the halo effect, definitely a halo effect. If we could see that there's a desire to move this forward, it would be really unfortunate if we continued with the scheduling because it would make the friction of making that available to patients and parents for their children would be high and, it, we just, we see a challenge with the access issues then.
Perfect. Maybe we'll move on to lucerastat in Fabry. The company recently presented some new data at World and kind of unveiled the phase 3 trial design. Can you kind of touch on the potential benefits of lucerastat versus Fabrazyme and Elfabrio and kind of how you see it being differentiated?
Lucerastat is an oral, it's an oral substrate reduction therapy, that itself is a huge advantage for patients who are trying to avoid the infusion burden. In addition to infusion burden, there is also a significant sort of signal sometimes of antibodies that develop to the enzymes, the Enzyme replacement therapy. We're very, very excited about having a pathway forward on lucerastat. It's something we've been committed to for a while. We did a 43-month open label extension, which we reported on at the WORLDSymposium in San Diego. In terms of, you know, where we are, the data is incredible for safety and tolerability.
We have close to six years in some patients of safety and tolerability for an oral, huge, you know, unmet need in this space because it's broadly applicable. It's not mutation dependent. We have a oral substrate that reduction therapy that can be applied to any adult patient, potentially with Fabry disease. In addition, the renal sort of impact and sort of slowing the eGFR, we saw in the MODIFY open label extension compared to historical data based on the patient's medical records. The trial design that we're moving forward is the pivotal that includes a baseline controlled biopsy.
A renal function study that's based on eGFR as a switch study so that we can show that patients do as well on lucerastat as they had been doing on standard of care, which is ERT. Super exciting program. The competitive landscape has been, you know, just definitely in favor of Idorsia potentially being one of the first broadly applicable oral substrates because as you might have seen recently, Sanofi's program also did not meet the primary endpoint for Fabry. They did very well in Gaucher, they didn't meet the primary for Fabry. That's actually for us, really a positive signal, not only from the competitive landscape, but we would love to start to think about other ways we could apply lucerastat in other lysosomal storage diseases.
Is there any additional data that you could, I guess, develop in-house before making that decision to go into other LSDs? Kind of what will be the trigger? Would you want to see the longer term data from some of these newer studies for Fabry before doing that? How are you thinking about product development?
I think, in terms of the overall development, I think our primary focus is to make sure we can get lucerastat to patients with the broadest label possible as soon as possible. We'd love to make sure that we deliver on the pivotal and that we can move the eGFR study along, as fast as possible. Then, of course, our research teams are going to continue to look at other potential areas. We'd love to broaden the applicability of the mechanism of oral substrate reduction beyond Fabry.
A filing, I think, was guided towards the 2029.
Yeah
... timeframe.
Exactly.
I guess what is the most important? Obviously, we need the biopsy study. Do you need a certain safety database before you can file and, you know, from that eGFR study as well? What are the components that would kinda make that together? If anything's gating to that final filing?
I mean, we're always in ongoing conversations with the FDA, and pending the results of the pivotal study, I think we'd love to continue the conversation with the FDA and file as soon as possible. It's possible that we could, you know, file with the amendment from the eGFR data. I mean, I think we had a 53% continuation rate on the open label extension, so we have quite significant safety and tolerability data right now. We are looking really to kind of just make sure that the FDA is comfortable with the pivotal.
While we did a kidney biopsy substudy as part of the open label extension, it was small because we focused on the male classic patients at the time, and it was not baseline controlled because it was in the middle of the open label extension. The bliss bodies, compared to what we would have anticipated the bliss bodies based on natural disease progression, was very much suggestive of this having the effect. We're looking forward to initiating and moving that trial forward, and we will have ongoing conversations with the FDA around the most expeditious path.
Perfect. Maybe we'll jump over to the other, commercial therapy, Tryvio. Can you just talk a little bit about the progress here? You know, we've been looking for a potential partner here, we can get into that as well. Maybe what is the therapy doing now? How is it differentiated? How much is Idorsia willing to invest in the franchise, maybe outside of a partnership?
Tryvio is approved in the U.S. as Tryvio. It's aprocitentan. It's approved in Europe, Canada, and the U.K. as JERAYGO, in Switzerland as JERAYGO. I mean, for us, this is really one of the hallmarks of our legacy. It's the fourth endothelin receptor antagonist that the Clozel have worked up and have been working in the endothelin receptor antagonist space since the eighties. Really this one is unique in that it's worked up for systemic hypertension. The differentiation of aprocitentan or Tryvio/JERAYGO is super evident, right? It's we did the trial with an eGFR down to 15, which is in co-comparison to some of the other products coming into the market and available assets. We don't see signals for hyperkalemia or hyponatremia.
In addition, the fact the label is actually quite broad, it's applicable to not adequately controlled on any, on one or on any other therapy. We are seeing the medical value because we've had it on market now, with a very small effort focused on hypertension centers, where we see huge medical value in patients that are truly resistant by definition, so on three or more therapies, those which have comorbidities that are endothelin linked and, those with CKD stage three and four. We're extremely excited that we can show the medical value. We're seeing the prior authorization being much smoother in those patients with the established medical value. The physician uptake on having a different MOA that's additive to current standards and sort of the current you know, the ASCVD therapies is quite good.
The fact that the side effect profile is very manageable, we're very optimistic that, you know, from the differentiation perspective, this is truly the first innovation targeting a new pathway in close to three decades.
Maybe on sort of the partnership opportunity, I guess what would an ideal partner look like to maximize value for this franchise? Maybe we started obviously talking about the balance sheet at the beginning of the time here. How would that kind of tie into sort of additional flexibility or stability on the balance sheet, you think?
TRYVIO is one of the assets that's in the asset backed vehicle, which is where we have sequestered our debt. The timeline for that debt payback is in the 2048, 2050 timeline. That being said, of course, it's important to us to make sure that we get this medication to this innovation to patients as soon as possible. As we think about the partnering strategy for Tryvio/Trigo, I think we've sort of looked, you know, from a range of partners, including just large scale strategic partners to more focused regional players. In all in the spirit of trying to ensure that we can maximize the value.
As we think about some of the dynamics and U.S. pricing dynamics, especially with MFN, we have an asset that has two different brands, two different doses, and two different indications. The indication in the European label is much more specific to persistent hypertension. We have been exploring the option to have regional deals so that we could think a little bit about, you know, how do we maximize it with a commercial partner in the U.S. that can navigate the U.S. commercial system, and then a European partner that can help make sure that we take it through the access dossiers and get it established in the European system. The ideal commercial partner, I think, in the U.S., is really one that is focused, you know, in the cardiology, nephrology space.
We do think that this has to start at the top of the pyramid with key opinion leaders who are really driving hypertension. We are in the ACC/AHA joint guidelines that we were the first innovation to be included in the joint guidelines earlier in 2025, which helps, I think, with the clinical practice. I think if we can start at the top of the pyramid and really establish it, then we'll see the follow-through in the broader cardiology, nephrology space. Because the label is so broad, I think once we establish its value, we can, you know, start to establish it in other patients. On the European side, I think we're looking at early market access work to understand how we can think about the patient populations.
Great. Maybe we'll dive into the earlier pipeline, but maybe if you can give us a little bit of a progress update on the CCR6 antagonist for skin inflammation, maybe where does that sit in the clinic? Then, you know, would you look to do as some others do, where you almost do like a proof of concept in psoriasis and then kinda see where you wanna go from there?
We've initiated our CCR6 program. I think we're, you know, a handful of patients into the program. It's a proof of concept slash proof of mechanism. We're doing it in psoriasis because the PASI as a test is a very clean test. We also know from the T helper 17 mediated mechanism for CCR6 and the ligands, like, we're actually kind of seeing, we can see a clean result on it. There are a range of indications that could be explored once the proof of concept is established.
Of course, I think we would love to see how the results pan out, but either you know, potentially with a partner or in other indications, like they could take this forward, either as an oral in psoriasis or in other, those other T helper 17 mediated diseases. It is initiated. We're very excited to kind of keep moving forward on potential growth drivers. Also, I think our philosophy, given our very, very rich pipeline, is that we should lead where we can, but partner where we should. If we find that the indication is very clean in psoriasis and it's not an indication that we necessarily wanna move forward in from therapeutic area cohesion, then I think we're very, very open to finding a right partner for that.
Maybe similar question for CXCR7 for progressive MS, kind of where does that pipeline product stand? Similarly, I mean, MS is challenging, I guess what would you be looking for as sort of in the initial datasets as signs of activity maybe to further invest in the program or kind of take it to the next level?
We're very, very excited about CXCR7 our antagonist for CXCR7, because it has the potential not only to have anti-inflammatory benefits, but also to have remyelinating benefits. We're in the process of initiating that trial, and we hope to announce that initiation in the coming, you know, or the quarter or Q2 latest. In terms of the proof of concept design, I think some of the endpoints that we're looking for are imaging, to kind of show the potential for remyelination as well as visual evoked potential. You know, we've designed this trial to really understand it. In progressive MS, again, you know, this may not be a therapeutic area that we have the scale. We have the history, right?
With Viatris, we were able to find a partner that was able to take the scale of both the AMI and the lupus trials forward with, you know, they were at the peak, I think they were enrolling more than 1,000 patients a month.
Mm-hmm.
You know, for the types of trials and the length of those trials, we may be looking for a partner. For us to know that we have an oral potential in this space that is, you know, similar, and has the potential for remyelination, I think is quite exciting, and we'd like to take that at least to the proof of concept stage.
Great. The last pipeline asset, maybe not the last in the company, but the last one that we'll maybe hit on is the CXCR3 for vitiligo.
Yeah.
I guess what have you seen either pre-clinically or not to get you excited for vitiligo as an indication and where does that program stand?
Vitiligo is super interesting because this is one where the current standard of care is in the JAK inhibitor space, and the toxicity from JAKs is quite strong. What we're trying to do is potentially disrupt the specific melanocyte targeting by antagonizing the CXCR3. You know, the various ligands that bind to the CXCR3, which drag them to do the destruction and sort of the memory of destruction of these melanocytes. We are hoping that we can, in the animal models, we can do something where we can even contribute to repigmentation because we're disrupting that gradient that's dragging these cells to destroy the melanocytes. We're thinking about potentially initiating that trial later this year.
It also very exciting and huge unmet need, right? Without any orals, there's some things kind of coming down the pipeline. Right now with topical JAKs and the sort of the side effect profiles from the JAK inhibitors, it would be a real game changer.
Awesome. Well, I think the company's done really well over the past year and a half here to kind of, as you said at the beginning, provide a lot of different avenues for value creation. Good luck, and hope you have for the rest of the conference.
Joe, thank you very much. We have a great team and so thank you. I think, you know, I came in in July, but the great team that's been working on the OPEX, that's been working on moving the programs forward despite some of the financial challenges, so really grateful for the opportunity to be working with them.
Thank you very much.
Thanks, everyone.