To the Idorsia session of the 2025 J.P. Morgan Healthcare Conference. I'm Sophie Brey, a member of the European Pharma team, and today it's my pleasure to introduce André Muller, CFO of Idorsia. Before handing over to André, just a reminder, I'm sure you've been in plenty of these sessions already so far. If you'd like to ask a question, raise your hand during the Q&A and we'll hand a microphone over to you. Otherwise, you can submit a question via the portal. Over to you, André.
Thank you and thank you for hosting us this year once again, and I hope, of course, to be with you next year. Yeah, thanks for all of you attending here and those in Europe who stayed awake very, very late. You've seen us in the news, and as you can imagine, we are fighting to create value for all stakeholders. So I will give you some color on what needs to be done in the immediate future and also give you our views that we believe we can achieve midterm. I will speak of the immediate short-term and midterm futures, so we'll make some forward-looking statements. So with this disclaimer, you're properly warned on the risks and opportunities to invest in Idorsia stock. So first, that's really our short-term.
Covenant pre-requisites for us to continue our operation are the four that you can see here, and it's a comprehensive plan that we believe can be achieved. First, we need to get an Aprocitentan deal. We need to complete the operational restructuring, which is almost done. We'll need a balance sheet restructuring, and you may have seen the recent announcement that we convened a bondholder meeting to amend and extend the terms of the 2025 bond, which would mature by the end of this week, and we would need additional funding to remain going concern. First, speaking of the Aprocitentan deals that we try to strike. As you know, Aprocitentan is the third drug we got approved in the last three years. 2022, we had QUVIVIQ, 2023, Clazosentan in Japan, and 2024, Aprocitentan.
So aprocitentan is an endothelin receptor antagonist, well known actually by our team, previously with Actelion and now with Idorsia, with actually aprocitentan being the first ERA to be approved. We had first Tracleer, Bosentan, then Opsumit with macitentan, then clazosentan, which has been approved in Japan, and now we have aprocitentan. So aprocitentan is approved in the U.S. under the brand name TRYVIO and in Europe under the brand name JERAYGO. You have seen our news by the end of November. We announced that we entered exclusive negotiation with an undisclosed party for the global rights of aprocitentan, and this undisclosed party paid an exclusivity fee of $35 million. As you can imagine, you know, this partner does not take such a decision lightly. We agreed on the terms.
We agreed on the timelines, and for different reasons which are not within our control, the company has told us that they are still interested in an appropriate entrant and getting this deal over the finish line, but I believe we'll not be able to achieve it in the next few weeks, possibly next few months, so that's where we are, and of course, we were really counting on the upfront that we would have received in connection with this deal. It's a good deal for us. Yes, and you will see it a little later. In my view, we would have preferred to a more front-load CRS deal, but globally, should we be able to strike this deal, it's a good deal for Idorsia.
Unfortunately, we are planning for our future and for success, but we had to reduce by the end of 2024 our cost base. This came after a significant restructuring already in 2023, where more or less 50% of our R&D organization was cut, and we had to further reduce by the end of 2024, mainly in drug discovery and clinical development, plus some support functions. We have roughly cut 250 positions globally, mainly at our headquarters in Switzerland, in order to keep a small and nimble R&D approach. Beyond the 250 positions that we had to cut, we hope that some of the employees could actually join the partner for aprocitentan should we be able to close the deal in the coming weeks or months.
Now, with this reduced R&D organization, we also had to reduce the number of projects that we have in our portfolio, and that's why we really prioritize preclinical and early-stage clinical assets with the objective to go to the proof of concept and see then whether we should partner the compounds or should we bring them to the next stage. The third part of these prerequisite short-term priorities is the balance sheet restructuring. As I alluded to it, you know, we have 200 million bond, which was already extended from July with a maturity in July 2024 to January 2025, because we strongly believe that these six months would have been enough for us to get the deal with the undisclosed party regarding aprocitentan.
And we have also another bond outstanding of CHF 600 million, where we call it bond 28, but the investors are likely to request the redemption in 2026, August 2026. So in any case, beyond the extension of the CB 2025, we'll need to restructure both bonds, so the CHF 200 million and CHF 600 million bond. And as I told you, we need a bridge to fund the company in the near term, and we'll show you where we land in terms of cash by the end of 2024 and what does it mean in terms of cash runway. And we will need also, because should we close the deal with aprocitentan, based on the terms negotiated with the undisclosed party, we will need to raise additional cash.
Given the time frame, we believe this will be most likely with incumbent stakeholders who have a vested interest today in Idorsia, potentially with third parties. You know, coming from Switzerland, we have a lot of, we have a lot of mountains, as you know, and if you climb as many Swiss do, usually the view from the top is really nice. Here at Idorsia, don't need to go too much outside to climb mountains because I have a mountain to climb here with my colleagues, of course. I want to share with you what could be the view from the top, should we be able to reach the top. In our view, and I hope you will share our excitement, the view would be quite amazing. Key strengths. First, we have an approved drug, QUVIVIQ. It's a different kind of insomnia treatment.
There's a need for innovative treatment for chronic insomnia, and we'll come back to it in a few slides. We have already partnered some of the assets, including QUVIVIQ. We have strong alliances that will allow us to maximize the value of our portfolio. We have, as I mentioned, a pipeline, even prioritized, but with promising in-house assets, most of them fully unencumbered. We have, despite the restructuring, we had to enter into RIFs by the end of 2023 and recently in November, December 2024. We have a specialized drug discovery engine, and we have also our R&D people, highly qualified professionals. I'm sure you've heard it from many biotech companies. I would say on top of being highly professional, you know, they're highly dedicated and they have shown resilience in a context which is not easy.
Moving forward, we need to see if the prerequisite sets our momentum to climb. If we get there, we have this dual model. On one hand, we have the Idorsia-led business, you know, mainly today with QUVIVIQ, potentially moving forward with additional drugs that we would keep and commercialize around the globe. And today with QUVIVIQ, mid-term, we have a plan to achieve sustainable profitability, not only commercial profitability, but with a reduced cost base, overall profitability. On the other hand, we have the partner-led business, and with this, we should be able to accelerate overall profitability through the milestones we would be entitled to. And with the tiered royalties, we would get piggy and we would piggyback on the success of our partners.
So now we have reset, I would say, the strategic priorities at Idorsia, and I will go through these five key priorities in the next few slides. First one is QUVIVIQ. Drug is approved. Drug is approved in the U.S. Drug is approved in Europe. Drug has been recently approved in Japan. Drug will be soon approved in China. So we have a drug which is approved in the U.S., unfortunately with a Schedule IV. And we believe that we launch a citizen petition in order to get the de-scheduling, not only of daridorexant, but of the full DORA class, so dual orexin receptor antagonist. And we are making good progress. If you have questions, Tosh Butt our President and General Manager for the U.S. will be happy to take any question.
Looking at the performance in over the past quarters, you see that we have been able to maintain the sales at a steady state of $758 million, so CHF 7 million over the last few quarters, including 2024. Despite reducing significantly the marketing and selling efforts, first, with the field force, you see that we have reduced the field force to what is now 91 reps in the field. We have also switched from TV ads campaigns because it is a primary care drug and it is driven by prescription with the GPs to digital marketing, which is quite successful. You see that we are able now to maintain this sales level around, give or take, CHF 30 million despite reduced OpEx. Europe is completely different. Within Europe and Canada, we call it UCAN. We have in each and every country a different status.
You have right now four countries where we are reimbursed: Germany, U.K., France. In Canada, we have private access coverage, which covers more or less 55% of the Canadian lives, and we applied for reimbursement in the public space. All other countries are out of pocket, but we are making good progress, notably in Spain, a big country where we aim to get reimbursement in the course of 2025, and you see here the acceleration. Look at Q4 compared to Q3, mainly driven by two countries: Germany reimbursed and France. Stellar launch in France, which was accelerated because we have only field force for the specialties, so psychiatrists and neurologists, but we partnered for in a co-promotion deal with Menarini, which has a huge GP sales force, and we have seen the acceleration the week after Menarini was calling on doctors.
We aim to repeat this type of collaboration in most of the European countries in order to really leverage the potential with the GPs. And you will see the guidance for 2025. You will see that we continue. We are very bullish, notably in Europe, on the potential of QUVIVIQ. In addition to unlock value, we want also to bring some phase four studies for all HCPs that have to treat insomnia and comorbid diseases. You may have seen and will publish soon the result of a phase four study in nocturia, which is really an impressive outcome. And we have other phase four, which provided that we would get funding, we would launch, plus the phase two in pediatric, where we expect results in the second half of 2025. And showing also the need of the physicians' community, we have many, many investigator-initiated studies ongoing or in preparation.
You see here the list, and we strongly believe that daridorexant can address some of the unmet medical needs in Alzheimer's, in PTSD, and in drug abuse or smoking withdrawal, or for women with menopause-related insomnia, or patients in OSA, Obstructive Sleep Apnea. So a lot going on, which is, again, investigator-initiated, showing the interest of the physicians' community for QUVIVIQ. Now, speaking of the existing alliances, first, we have QUVIVIQ with Nxera, and as I told you, they just launched with their local partner, Shionogi, daridorexant in Japan. We have also Simcere in China. They conducted a bridging study, which was really successful. We had no doubt that we would be able to repeat with this bridging study the stunning results that we've seen in the pivotal trial, global pivotal trial. Simcere expects to get an approval by the end of 2025 and launch right after.
We have also inked a deal with Viatris back in by the end of Q1 2024 for two promising phase 3 assets, Selatogrel. We call it our cardio pen for suspected AMI, so it's an auto injector, and cenerimod, which is currently investigated in SLE. Both trials are recruiting fast thanks to the expertise and the financial muscle of Viatris. We have a vested interest in the success with the milestone, regulatory sales milestone, and royalties. Speaking of the late-stage pipeline, one which is with phase 3, unfortunately, that could not meet the primary endpoint on neuropathic pain was lucerastat for Fabry patients. What we have seen is a unique and marked reduction in the kidney function, i.e., the decline in or the slowdown of the decline in the eGFR slope. To this extent, we had 118 patients in phase 3.
Most of them, to the request of the physician, entered in an open label extension. And if you're looking at the wealth of data that we gathered, you know, we had now, as you can see, more than 60 patients which have been treated for at least two years, more than 30 patients treated for more than four years, and even some patients for up to six years. So if we can confirm the reduction in the kidney function decline with this open label, this would open up, of course, a discussion with the FDA. Also, we're in connection with the kidney biopsies where we expect to get the results early Q2 2025. So this is still ongoing, and this would be the fourth drug, hopefully, that would be approved in Fabry.
Speaking of the early stage, not going too much in detail here, with me, I have Martine Clozel, our Chief Scientific Officer, who will be able to take any of your questions. We have three antagonists where we believe we have a unique or first-in-class potential, one called CXCR7 or ACKR3, which could be investigated in progressive multiple sclerosis. And here in MS, the Holy Grail is not only to decrease the inflammation, it's also to have remyelination. And we have shown in animal models that we could have this unique combination of remyelination and anti-inflammatory effect. We have CXCR3, which we could investigate in vitiligo, but could be investigated in many other immunodermatology and autoimmune disorders. And we have CCR6, which could be also phase one is ongoing. We are waiting for results of this phase one, but could be, again, investigated in immunodermatology or autoimmune diseases.
Lastly, we have never disclosed much about our preclinical pipeline, so I will, conscious of time, not go in each and every compound. Again, we believe that for each of them, we have a potential best-in-class for these compounds. If anyone is interested, please come and see us. The only thing which cannot be a partner is the CFTR because we are under exclusive discussion for this CFTR corrector in cystic fibrosis. Lastly, we have also a synthetic glycan vaccine platform that we developed with the Max Planck Institute. We have an ongoing phase one in Clostridium difficile, and we have also in preclinical pentavalent Klebsiella pneumoniae vaccine. As I said, because of the restructuring, you see that we drastically reduced the number of preclinical projects. We went from 16 to 8.
Most of them were presented to you, at least for CF4, and plus one for CF vaccine. CF2 also includes what I just mentioned regarding C. difficile. The last point, which is, of course, critical, is to make the money last. We ended 2024 with cash above CHF 100 million. With this cash, we extend the cash runway until the end of Q1 2025 because the lasting effect of the restructuring will only kick in early April because mainly the notice period of our employees. Here, I can tell you, we confirmed the guidance we gave with the half-year results, resulting in CHF 330 million non-GAAP EBIT, excluding non-cash stock-based compensation. One of the deals you see here, so CHF 125 million, this was in connection with the deal with Viatris for selatogrel and cenerimod earlier this year in 2024.
Moving forward for 2025, of course, here you have a big caveat, excluding unforeseen events, and provided that we can address the short-term funding, we would significantly increase the revenue. You see here, we would go from CHF 55 million to CHF 110 million next year. That's to be clear, Idorsia-led business, it's only QUVIVIQ. So QUVIVIQ in Europe and Canada for approximately CHF 80 million and CHF 30 million that we believe we can maintain in the US. You see over time, with all the efforts that we have done, we reduce markedly our operating loss, roughly CHF 600 million in 2023, CHF 350 million in 2024, and going to CHF 200 million, slightly above, in 2025. As you can see, we are fighting to create value for all stakeholders. Thank you for your attention, and we are happy to take any calls. Any questions, sorry. Coming next to you, Sophie.
Thank you for the presentation. Are there any questions in the room? If not, maybe could we start with beyond aprocitentan and the discussions you're currently engaged in, as well as the earlier stage assets which you've highlighted. Could a further partnership for QUVIVIQ in another region be a consideration you would enter into?
Yeah, if we find the right partner, recognizing the values that we have created over the last few years, yes, clearly, we would be ready to do so.
Maybe if we could just talk about the progress then of QUVIVIQ in some of these regions. Could you elaborate on some of the reimbursement discussions that you're having currently within Europe?
You know, as I mentioned, drug is reimbursed in Germany, in France, in the U.K. We manage, you know, it's quite unique.
First, in Europe, it's quite unique because the other DORAs, be it Dayvigo or Belsomra, are not approved. So we are the unique treatment, the only alternative to treatment. We know, notably, Z drugs or Benzos, which have some significant safety issues. So now that we have secured reimbursements in these countries, we are looking to expand the field force by having co-promotion agreements with selected partners in each and every of these countries. As I said, Italy, we manage, we have not been successful to get reimbursement in Italy, but at least we manage to get access to be granted by AIFA access, not only to see a specialist, be it psychs or neuros, but also to see a GPs. So we're looking with who could be the best partner to help us to call on the GPs in Italy.
Spain will be more or less what we have experienced in Germany and France. We should get reimbursement second half of 2025, and we are also actively looking for a partner that could leverage where we could leverage their footprint in the GPs space. Maybe could you talk a little bit about the typical profile you're seeing for a QUVIVIQ user? And does that vary between either geographically or in reimbursed or out-of-pocket markets? If you are out of pocket today, yes, of course, it comes with a cost. So it's a combination of cost burden for the patient, especially for chronic users, not only entirely because of us. If I look at the cost for patients in Italy, it's EUR 3, but it's EUR 2 net selling price for us.
And a combination of awareness of a new medicine which can really address the chronic insomnia of some patients severely impaired. And so it's a combination of both. But what we aim as if this is possible, and we believe we can achieve reimbursement in Spain and other countries like Switzerland, like Austria, like Sweden, and where we have affiliates, and also in Canada because we filed for reimbursement in Canada as well. What are you seeing in terms of adherence rates now from patients? When patients do discontinue, what are the factors that are driving that? Well, we see it's different between the US and Europe. And Tosh, I will defer to you to explain where we are in the US.
For those patients that are initiated on 50 milligrams, we have shown in the pivotal trial that you have better efficacy, and it did not come at the detriment of safety. So with 50 milligrams, we see a much better adherence to the treatment. So if you get it reimbursed, you see that you've seen the volumes going up, and that should continue to go up moving forward. In the U.S., we see a similar pattern, except that the treatment pattern from a physician starts low and increases the dose. And actually, what we are pushing, but with limited field force now, is to say, no, look at your data. We had 1,800 patients with efficacy and over six months safety over more than 12 months. Look at your data. You should start them with 50 milligrams.
And in the US, we see a refill rate, which is three times higher with 50 milligrams compared to 25. Interesting. You've also touched upon the reduction in field force that you've seen, but balancing that with continuing to drive growth in QUVIVIQ. Could you elaborate a bit more? I know you mentioned the digital element, but how you've changed the approach to scaling the product and reaching your target audience? Tosh, maybe you can take this one. I don't know if we have a mic or you come here. There's a mic over there. Maybe take the mic from this gentleman. Thank you. What we've had to do through necessity, as André has described, due to the financial circumstances we're under, we've had to take some pretty tough decisions on resourcing of QUVIVIQ in the US. We've taken those decisions.
You've seen the dramatic reduction in the field force size, and you've seen us really take a lot of the learnings over the last two years with our digital online spending. We've really refined our search. We've really refined the positioning of our online ads, and you can see that it's managed to sustain that launch momentum, which we're really happy about, and we're also pleased to see the question around adherence and refill rates. Our refill rates have also been continuing to improve since we've launched, and that's a function of, as we call on more and more doctors, as we call on them more frequently, the message is landing that if you start on 50 milligrams, they'll get a better night's sleep. They're less likely to feel tired and groggy the next day, which leads to greater patient satisfaction.
Ergo, they start to fill their prescriptions more often. As André said, between two to three times the rate we're seeing if they initiate patients on a 25 milligram. So we've just really taken all the learnings the last two and a half years and really applying the money in a very, very focused manner. And it's allowing us to sustain our business. Thank you. And just one final question, if there are none in the room. How do you now see the peak sales potential of a product like QUVIVIQ? It will depend. If you take U.S., it's a primary care drug. So we would need to put resources behind. As said, when we see today's inertia in the market, we believe that the scheduling will be a big inflection point.
Because today, we have some step edits with other drugs, including sometimes Z drugs or Benzos, and even including Trazodone, which is an antidepressant, not even indicated for sleep disorders. So this would be removed if we have the scheduling. But it will require, it will in any case require marketing and selling efforts to properly call on doctors. So we see if it's better for us to do it alone, provided we would have the funding because the expertise is available, or if we would do it with a partner. And here, we remain very nimble and will see what is best for QUVIVIQ in the US. Great. Thank you very much for your time.