Jazz Pharmaceuticals plc — Call Transcript 2026

Hello, everyone. My name is Etzer Darout, Senior Biotech Analyst at Barclays. My pleasure to have Jazz Pharmaceuticals with us today. On stage with me, I have Phil Johnson, Chief Financial Officer, and John Bluth, Head of Investor Relations. Thank you so much for joining us today. Phil, I'm sure folks are relatively familiar with Jazz, but maybe just to kick us off, just provide some introductory remarks, and then we'll go into our Q&A. Yeah, I'd be happy to. Thanks, Etzer, for hosting us here, and this is a great location to be in and a great time of year to be down here in Miami Beach. Just a disclaimer, please do, as we're going through the discussion, if there's things you're interested in learning more about, including risks that can affect our business, please do refer to our recently filed Form 10-K. If we do refer to guidance during the discussion today, that would be the guidance we provided on our recent Q4 earnings call. 2025 was a great year for the company and really sets us up extremely well for 2026. I think had important advancements in commercial, the pipeline, as well as in corporate development. I'll touch just briefly on each of those. On the commercial side, in 2025, we had record revenue for the company growing 5%, driven by 12% growth in Xywav, 9% in Epidiolex, and initial uptake of Modeyso that was quite strong. That was our 21st consecutive year of growth. It was a pretty outstanding achievement for any company. We're really proud of that accomplishment. On the pipeline side, had a couple of really incredible pieces of data come out, practice-changing data in first-line maintenance small cell lung cancer with our product Zepzelca in combination with atezolizumab. Probably most importantly for the company, the first-line GEA readout of zanidatamab, where we showed unprecedented overall survival results extending beyond two years. On the corp dev side, had a really interesting acquisition, both from a patient perspective, acquiring Chimerix with their drug, dordaviprone. Shortly after the acquisition, we're able to get that approved and launched off to a great start. Also from a financial perspective, I think it's shaping up to be a phenomenal return for Jazz and Jazz shareholders as we acquired deferred tax assets that will reduce our cash taxes over time by over $200 million. We also received a priority review voucher with the approval of Modeyso and sold that, I think, for at least a 10-year high of $200 million. Really pleased with that deployment of capital. As we come into 2026, we provided guidance that was $4.25 billion-$4.5 billion in revenue for the year. That would be 2.5% growth at the midpoint, meaning we are aiming for our 22nd consecutive year of revenue growth as a company as well. On the pipeline side, one of the biggest events people are looking for is approval and launch for zanidatamab in that first-line GEA setting. Initially, we've been targeting a submission to the FDA in the first half of 2026. On our fourth quarter earnings call, we said that would be in the first quarter. Then at a recent conference, I won't mention the name, we had confirmed we actually already have submitted to the FDA. Post the data being available, the FDA had included us in the RTOR program, the Real-Time Oncology Review program, and then more recently assigned Breakthrough Therapy designation for zanidatamab in first-line GEA as well. We're optimistic that we'll receive a priority review and look forward to approval and then launch of the product later this year. On corporate development side, we're really well-positioned, I think, understanding the substrate that's out there in rare diseases of interest to us and with great financial resources to be able to act $2.5 billion roughly in cash and investments, strong ability to leverage if we need it for attractive opportunities and additional focus that we've placed on corporate development with the hiring of a Chief Business Officer, Tom Riga, dedicating additional management time and focus to those efforts. Confident we'll be able to find really good opportunities for us to deploy capital, improve outcomes for patients, and drive greater returns for shareholders as well. Great. Thank you for that, Phil. Maybe just internally, when you think about investments. In the business, obviously, sleep franchise, epilepsy franchise, huge components of the company today. You have this growing oncology business with Ziihera hopefully continuing to grow as we get more and more clinical updates. How are you thinking about sort of resourcing CNS relative to oncology just internally in how you kind of think about that business over the next couple of years? Yeah. We've got great opportunities sort of in that non-sleep portion of our business. As part of the guidance, we did say that revenue, which is over half of the company's total revenue in 2025, we expect to grow double digits here in 2026, continued growth of Epidiolex, and then obviously ramping for Modeyso and growth in Ziihera as well. We are extremely focused in terms of capital allocation on investing behind the existing marketed products and making sure that we're getting those to patients who can benefit from them and driving revenue there. That is what pays the bills and gives us the resources to invest. Secondarily, really making sure that we're investing behind the existing pipeline that's in-house now. We've got some great opportunities, first and foremost, probably to build out indications for Ziihera. Certainly a high priority, as I mentioned earlier, for us to go ahead and increase the company's future growth profile through additional corp dev. As we think about the areas where we're currently operating in, sleep, epilepsy, and oncology, as you look at the substrate there is the most interesting innovative science, probably in the epilepsy space and in the oncology space. In sleep, which I'm sure we'll talk about going forward. Orexins are currently the only sort of real innovation coming forward. That may change over time, and we'll continue to look for opportunities to grow that franchise as well. Definitely beyond the areas that we're currently in, we see some really good opportunities in rare disease to go ahead and expand our presence, use our capabilities, to drive great outcomes for patients as well as for investors there as well. We haven't yet done that, so I know we've been saying this for a few years, but I wouldn't be surprised if in the coming quarters or years you're seeing us expand into one or more new rare disease areas beyond those that we're currently in. Yeah. People, we tend to have short memories, so we think about the Modeyso transaction as sort of being a recent one. Just maybe looking forward, is that maybe a framework in terms of what we could see from Jazz and just in terms of sort of the deal type, deal size? Yeah. Definitely would love if we could find some more Chimerix's to acquire. I would say that if you think about where we'll be investing, in the areas we've got existing deep expertise, knowledge, and relationships, we'll invest across that full spectrum from marketed products all the way to preclinical. The Saniona licensing deal that we did last year in the epilepsy space is an example of that. If we're going into new areas of rare disease, which I mentioned I expect that we will do going forward, those initial investments would likely be targeted to things that are post proof of concept or at least proof of mechanism with an improved compound going after that mechanism. As we build that expertise, knowledge, and relationships, begin to invest earlier in clinical or even preclinical development. Great. Maybe onto the sleep franchise and obviously Xywav, a great performance the last couple of years. You know, we have Lumryz, other generic oxybates potentially coming online as well, orexin agonists being talked about. Sort of your view on the durability, if you will, of the sleep franchise. Yeah. We're really pleased over the years with how Xywav has performed, not only in building out the idiopathic hypersomnia indication, where we're the only approved drug, and I think have been quite successful in building awareness of the utility of an oxybate for patients with idiopathic hypersomnia, but honestly also in narcolepsy as well, where I think many on the street, potentially even some internally, expected something different to happen than what really happened. You know, we've been continuing to build quarter after quarter the number of patients on Xywav with narcolepsy, even with the emergence of a branded competitor and the AG. It had, I think, even more net patient adds in the fourth quarter than the branded competitor did. I think it speaks to the unique benefit that Xywav offers, which is a safety benefit of having low sodium used in the patient population, whether that's those with narcolepsy or idiopathic hypersomnia, that have a two to three times higher incidence of and risk for cardiovascular events. We've got data that shows, for example, if you go from a high sodium oxybate to a low sodium oxybate, you see clinically meaningful reductions in blood pressure. This kind of benefit we think is resonating with physicians and patients. It's part of the reason why we're not only building the market in idiopathic hypersomnia, but having probably more durability in narcolepsy than many would have thought. I mentioned on our fourth quarter call, there were some accounts last year that had a step through the AG before you could get to one of the branded options, and we still had the highest share there. This benefit, which is a safety benefit, does resonate with physicians, with patients, and we'd expect to resonate with many payers as well. Great. You know, we've had conversations with different KOLs, and their views on orexin agonists in general seems to be varied. In your conversations with key opinion leaders around the potential impact of orexin agonists, what are you hearing from them about what that impact could be on the There's a great excitement for the orexins, not only in hypersomnias where we're operating, but potentially in patients with ADHD or Alzheimer's, Parkinson's, et cetera. We don't follow that portion of it as much, so I'll limit my comments maybe to talking about the role in hypersomnias. Certainly, orexins appear to be the most potent wake-promoting agents that we've seen to date, particularly in narcolepsy type 1 patients, which is where we'd expect to see the first application and approval of Takeda's product, potentially getting approved and launched yet this year. I think the role in NT2, the role in IH, is still to be played out and still uncertain. You know, Jazz for quite a number of years has been saying that we viewed orexins and oxybate as being complementary and expected there to be concomitant use, not that orexins would actually cure patients and obviate the need for oxybate. I think for many years, people looked at that as a maybe Jazz self-serving comment. There was hope, I think, that these orexin products might go ahead and be the cure, if you will, functional cure for patients with narcolepsy, particularly narcolepsy type 1. That does not seem, from our view, to be the way the data is playing out, and I think other, whether it's KOLs or other corporates, I think are also adopting the view that these will be complementary therapies. My expectation is that if a company's gonna spend $2 billion to get a company that has an oxybate and they already have an orexin, they're probably not viewing them as being competitive. Either would being complementary. Hopefully good news for patients with narcolepsy that this could be a more effective daytime treatment to use alongside an oxybate to help treat their symptoms and get better outcomes. Great. Maybe a couple of questions on epilepsy. You know, Epidiolex settlement looks to have a really nice IP runway. When you think about sort of maybe the growth profile or the growth outlook for Epidiolex, how are you thinking about that? Yeah. Really pleased to have had the ANDA settlements with the 10 ANDA filers that we announced last year in the early part of the year, giving us runway out to the very late 2030s. And the product last year grew nicely past that billion-dollar mark, and we see opportunities for continued growth of Epidiolex going forward. A number of places where we're focused, one I would highlight is in the adult patient population. Many of these are in long-term care settings. We've been expanding our outreach efforts there. Many of these patients also have LGS, a condition that takes over a dozen years often to be diagnosed, so we've helped with the REST-LGS tool to help physicians identify these patients. At times, there can be difficulties as someone goes onto therapy of getting up to and titrating to an efficacious dose and then staying on therapy. They're really effective Nurse Navigator program that's been rolled out to a minority of patients so far that we're looking to expand because we do see better experiences on product, including greater persistency, when they're having that additional support. We're also looking for ways to improve the product profile for those adult patients. We're working on a formulation that could make the product more attractive to adult patients and looking for additional ways that we can generate data to inform clinicians on uses of Epidiolex, including the phase one study that we recently mentioned. We're starting focal onset seizures as well. Beyond Epidiolex itself, with that long runway to the very late 2030s, this certainly is a franchise we'd like to build out with additional products, to have in the bag and build on our existing relationships, to benefit patients. How much of the safety tolerability observed with Epidiolex, how much of a differentiator is that in epilepsy? You know, most of these patients are on polypharmacy. They're typically taking three or more anti-seizure medications, and Epidiolex seems to combine very well and is often one of those medications that they're on. You even see this in some of the newer products coming through clinical development, where in a number of these cases you've had probably a third or more of patients that have been on Epidiolex in those studies as well. We do expect going forward there'll be additional innovative therapies that will help improve patients' reductions in seizures, but there will be a continued need for additional add-on therapies, and Epidiolex is well-positioned to be one of those. Right. Maybe a few questions on the oncology franchise. Let me first maybe lay out so you know, so seeing a sort of encouraging launch, maybe you can kind of speak to that, you know, what's sort of driving that and maybe how you see that evolving in the next few years. Yeah. We've been really pleased with the uptake of Modeyso. There's really been nothing for these patients since the advent of radiotherapy 60 years ago. We saw strong initial conversion of patients that were on the expanded access program. Of the 360+ patients treated in 2025, the vast majority of those were new patients. Really pleased with that adoption and uptake, including in those new patients, not just the conversion from the EAP program. This is a product we said we see having $500 million peak sales potential just here in the U.S. This early uptake is very encouraging. We're still reserving judgment on whether that $500 million should change or not.. I'll be monitoring two things over time to understand if that should be moved up. One is, do we get the epi right? Roughly 2,000 patients. Are there actually more out there that can benefit from Modeyso? And then secondarily, duration of treatment. We've been on the market since mid-August, so it's still early to know how long patients will stay on. You know, our first patients will get out to a year, obviously, therefore are going to be those that would have been out in August of this year. So by end of this year, I think we'll have a much better view on average duration of treatment, not just median, and be able to understand does that also influence the peak sales potential. Yeah, maybe you could comment on how much, how important is that frontline update on sort of that $500 million peak number in the U.S. I guess maybe how we should think about it. Could it be potentially more? Yeah. No, great question. The first-line use was included in that $500 million estimate when we had provided it. When we acquired Chimerix, we did make some adjustments to the ACTION study. We increased the number of patients by about 100. We changed the primary endpoint to be overall survival that we think is more appropriate, and that readout is expected in late this year or early in 2027, so look forward to that readout as well. We are approved in that recurrent setting. That's where we promote to, but we do know that given the unmet need there and the physicians see this as a very well-tolerated drug, that some of that early uptake is occurring in physicians using this in earlier line patients and first-line patients. Great. With, you know, we talked about the HERIZON update in gastric cancer readout, so great results. How are you preparing for that launch and that front line population? Again, extending that beyond, I guess you also have to kind of think ahead and potentially breast coming on in a couple of years. How are you thinking about that initial launch? Then how are you setting up hopefully for success beyond gastric? Yeah. Really excited to be bringing this to market in the not-too-distant future, given the kind of practice-changing results that we generated. The current indication is in second-line biliary tract cancer, and these are effectively the same physicians. Probably there's 90%+ overlap of the prescribing physicians for first-line GEA. These physicians are getting initial experience with the drug in those BTC patients. We think that initial experience will be very helpful as we come to market later this year. In first line GEA, then yes, the thing sort of up would be breast cancer. There we're studying metastatic breast cancer, basically in patients who have progressed after an HER2 therapy or intolerance to an HER2 therapy. Really the first one into generating data in that space, which right now is sort of a third line plus. With an HER2 moving into the first line, that would become more of a second line plus kind of indication. Enrollment's going quite well. We currently expect enrollment to complete in the first half of 2027, and then trying to use our best estimate on what we're seeing in events rates currently, that would be late 2027 or late 2028 for the initial readout there. That would be the final PFS and then the first interim OS. Right. You know, again, beyond this initial data set with this profile, there are various ways you can go. You can go into earlier-line breast cancer. There's also the tumor-agnostic approach around HER2 therapies. How are you thinking about that beyond the initial indications that you're currently executing on? We do feel like the data that we generated in that first line GEA study are pretty definitive proof that at least in that setting, we have a vastly superior targeted HER2 agent compared to Herceptin. Clearly we're looking where Herceptin was approved and successful, which is breast cancer and gastric cancer, looking for ways to expand there. That could be both early breast cancer, like you mentioned, adjuvant, neoadjuvant, also early gastric. Then we're looking at some places where maybe Herceptin didn't get approved, didn't quite meet the bar, but with a much more potent HER2 agent, we could have success. We're looking in non-small cell lung cancer. We have some really outstanding early results in colorectal as well that we're looking at. Even within the existing areas that we're in, trying to figure out what are ways that we can go ahead and improve the data that's available for physicians over time to inform use. Striking up partnerships with companies that have, you know, novel, could be best in class, HER2-targeted TKIs, for example, in breast cancer. We've got a recently announced collaboration with Boehringer Ingelheim, zongertinib, and then you'll probably expect to see more of that from us over time as we build out zani. There's the ongoing pan-tumor trial that you had mentioned that could also lead to an additional indications. That's a registrational quality and size study as well. Within oncology, there's other areas as well. You mentioned the frontline maintenance small cell lung cancer study. When you think about again, optionality around the oncology portfolio and in the pipeline, how should we think about sort of the rest of the oncology business for Jazz? Yeah. With Zepzelca, that first-line maintenance setting in combination with atezolizumab, really excited about those results. Strong overall survival benefit and very clinically meaningful benefit there. We would expect to see that become standard of care in that first-line maintenance setting. As far as how the overall product revenue progresses, that will depend on the dynamics in the current second line, which is the majority of use, where there is a competitor that has overall survival benefit that we would expect to become standard of care over time and our use in second line decline. And also, there's not data that we would point to that would indicate that we expect if you're getting Zepzelca in that first line maintenance setting, that you'd be rechallenged in second line. Again, really pleased with the benefit we can bring for patients in that first line maintenance setting. That's where we've been focused for quite some time. We'll continue to be focused there, but recognize that that second line business will decline over time. Then earlier on in the pipeline, you have, you know, again, a few different assets across different therapeutic areas of interest, one of which is the KRAS and G12D and NRAS programs. I guess, how are you looking at that space as it evolves and where you think ultimately Jazz could play a role in that space, again, given how much interest there is overall in the RAS space? Yeah. We've got a couple of phase I assets ongoing, NRAS that you mentioned, that's sort of in expansion cohorts now. We're pleased we're moving into that. We've got the conditionally activated interferon alpha that's moving into some cohort expansions as well. Pleased that we're sort of passing some of those initial phase I hurdles, moving into those either dose escalation, dose expansion, or cohort expansion studies, and have strong interest in solid tumors for each of those assets. We also, as Jazz has been transitioning over the last six, seven years, into a more fully integrated biopharma company, including not just early development, but actually preclinical development, our own research, we're pleased to have moved our first Jazz-generated asset into the clinic. This is in the epilepsy space. Still holding off on disclosing mechanism of action. We expect to see more assets coming from those efforts as well. While corporate development continued to be the primary source for us of getting new innovation into the company, assets like Ziihera, like Modeyso, we're really pleased. We're beginning to see sort of the fruits of the labor over many years to build the research capability that can generate interesting assets as well. Great. You know, we mentioned focal onset seizures as a potential long-term opportunity for Epidiolex. Maybe you know, the basis, if you will, for that is maybe some preliminary data that you've seen internally, maybe pre-clinically, physician feedback on maybe anecdotal evidence. Where what's sort of driving that? That as well as just clinical data you've seen. We're basically in, you know, specific diseases, if you will, as opposed to the seizure type, and we've seen benefits in focal onset. I do think we wanna make sure that we're thinking about how to best direct that development, to be consistent with our focus on rare disease and also the kind of pricing profile that Epidiolex has as well. Trying to find patient population where you've got a significant benefit that you can feel good about both the incremental outcomes that you're driving for patients as well as then the kind of pricing that you have for the product. Great. Bill, John, thank you so much for your time. Enjoy the rest of the conference. Thank you for our listeners, and we'll be back to our next session shortly. Thanks, Etzer. Appreciate it.

Speaker 1: Hello, everyone. My name is Etzer Darout, Senior Biotech Analyst at Barclays. My pleasure to have Jazz Pharmaceuticals with us today. On stage with me, I have Phil Johnson, Chief Financial Officer, and John Bluth, Head of Investor Relations. Thank you so much for joining us today. Phil, I'm sure folks are relatively familiar with Jazz, but maybe just to kick us off, just provide some introductory remarks, and then we'll go into our Q&A. Hello, everyone. hello everyone My name is Etzer Darout, Senior Biotech Analyst at Barclays. my name is etzer darout senior biotech analyst at barclays My pleasure to have Jazz Pharmaceuticals with us today. my pleasure to have jazz pharmaceuticals with us today On stage with me, I have Phil Johnson, Chief Financial Officer, and John Bluth , Head of Investor Relations. on stage with me i have phil johnson chief financial officer and john bluth head of investor relations Thank you so much for joining us today. thank you so much for joining us today Phil, I'm sure folks are relatively familiar with Jazz, but maybe just to kick us off, just provide some introductory remarks, and then we'll go into our Q&A. phil i'm sure folks are relatively familiar with jazz but maybe just to kick us off just provide some introductory remarks and then we'll go into our q&a

Speaker 2: Yeah, I'd be happy to. Thanks, Etzer, for hosting us here, and this is a great location to be in and a great time of year to be down here in Miami Beach. Just a disclaimer, please do, as we're going through the discussion, if there's things you're interested in learning more about, including risks that can affect our business, please do refer to our recently filed Form 10-K. If we do refer to guidance during the discussion today, that would be the guidance we provided on our recent Q4 earnings call. 2025 was a great year for the company and really sets us up extremely well for 2026. I think had important advancements in commercial, the pipeline, as well as in corporate development. I'll touch just briefly on each of those. Yeah, I'd be happy to. yeah i'd be happy to Thanks, Etzer, for hosting us here, and this is a great location to be in and a great time of year to be down here in Miami Beach. thanks etzer for hosting us here and this is a great location to be in and a great time of year to be down here in miami beach Just a disclaimer, please do, as we're going through the discussion, if there's things you're interested in learning more about, including risks that can affect our business, please do refer to our recently filed Form 10-K. just a disclaimer please do as we're going through the discussion if there's things you're interested in learning more about including risks that can affect our business please do refer to our recently filed form 10-k If we do refer to guidance during the discussion today, that would be the guidance we provided on our recent Q4 earnings call. 2025 was a great year for the company and really sets us up extremely well for 2026. if we do refer to guidance during the discussion today that would be the guidance we provided on our recent q4 earnings call 2025 was a great year for the company and really sets us up extremely well for 2026 I think had important advancements in commercial, the pipeline, as well as in corporate development. i think had important advancements in commercial the pipeline as well as in corporate development I'll touch just briefly on each of those. i'll touch just briefly on each of those On the commercial side, in 2025, we had record revenue for the company growing 5%, driven by 12% growth in Xywav, 9% in Epidiolex, and initial uptake of Modeyso that was quite strong. That was our 21st consecutive year of growth. It was a pretty outstanding achievement for any company. We're really proud of that accomplishment. On the pipeline side, had a couple of really incredible pieces of data come out, practice-changing data in first-line maintenance small cell lung cancer with our product Zepzelca in combination with atezolizumab. Probably most importantly for the company, the first-line GEA readout of zanidatamab, where we showed unprecedented overall survival results extending beyond two years. On the corp dev side, had a really interesting acquisition, both from a patient perspective, acquiring Chimerix with their drug, dordaviprone. On the commercial side, in 2025, we had record revenue for the company growing 5%, driven by 12% growth in Xywav, 9% in Epidiolex, and initial uptake of Modeyso that was quite strong. on the commercial side in 2025 we had record revenue for the company growing 5% driven by 12% growth in xywav 9% in epidiolex and initial uptake of modeyso that was quite strong That was our 21st consecutive year of growth. that was our 21st consecutive year of growth It was a pretty outstanding achievement for any company. it was a pretty outstanding achievement for any company We're really proud of that accomplishment. we're really proud of that accomplishment On the pipeline side, had a couple of really incredible pieces of data come out, practice-changing data in first-line maintenance small cell lung cancer with our product Zepzelca in combination with atezolizumab. on the pipeline side had a couple of really incredible pieces of data come out practice-changing data in first-line maintenance small cell lung cancer with our product zepzelca in combination with atezolizumab Probably most importantly for the company, the first-line GEA readout of zanidatamab, where we showed unprecedented overall survival results extending beyond two years. probably most importantly for the company the first-line gea readout of zanidatamab where we showed unprecedented overall survival results extending beyond two years On the corp dev side, had a really interesting acquisition, both from a patient perspective, acquiring Chimerix with their drug, dordaviprone. on the corp dev side had a really interesting acquisition both from a patient perspective acquiring chimerix with their drug dordaviprone Shortly after the acquisition, we're able to get that approved and launched off to a great start. Also from a financial perspective, I think it's shaping up to be a phenomenal return for Jazz and Jazz shareholders as we acquired deferred tax assets that will reduce our cash taxes over time by over $200 million. We also received a priority review voucher with the approval of Modeyso and sold that, I think, for at least a 10-year high of $200 million. Really pleased with that deployment of capital. As we come into 2026, we provided guidance that was $4.25 billion-$4.5 billion in revenue for the year. Shortly after the acquisition, we're able to get that approved and launched off to a great start. shortly after the acquisition we're able to get that approved and launched off to a great start Also from a financial perspective, I think it's shaping up to be a phenomenal return for Jazz and Jazz shareholders as we acquired deferred tax assets that will reduce our cash taxes over time by over $200 million. also from a financial perspective i think it's shaping up to be a phenomenal return for jazz and jazz shareholders as we acquired deferred tax assets that will reduce our cash taxes over time by over $200 million We also received a priority review voucher with the approval of Modeyso and sold that, I think, for at least a 10-year high of $200 million. we also received a priority review voucher with the approval of modeyso and sold that i think for at least a 10-year high of $200 million Really pleased with that deployment of capital. really pleased with that deployment of capital As we come into 2026, we provided guidance that was $4.25 billion-$4.5 billion in revenue for the year. as we come into 2026 we provided guidance that was $4.25 billion-$4.5 billion in revenue for the year That would be 2.5% growth at the midpoint, meaning we are aiming for our 22nd consecutive year of revenue growth as a company as well. On the pipeline side, one of the biggest events people are looking for is approval and launch for zanidatamab in that first-line GEA setting. Initially, we've been targeting a submission to the FDA in the first half of 2026. On our fourth quarter earnings call, we said that would be in the first quarter. Then at a recent conference, I won't mention the name, we had confirmed we actually already have submitted to the FDA. Post the data being available, the FDA had included us in the RTOR program, the Real-Time Oncology Review program, and then more recently assigned Breakthrough Therapy designation for zanidatamab in first-line GEA as well. That would be 2.5% growth at the midpoint, meaning we are aiming for our 22nd consecutive year of revenue growth as a company as well. that would be 2.5% growth at the midpoint meaning we are aiming for our 22nd consecutive year of revenue growth as a company as well On the pipeline side, one of the biggest events people are looking for is approval and launch for zanidatamab in that first-line GEA setting. on the pipeline side one of the biggest events people are looking for is approval and launch for zanidatamab in that first-line gea setting Initially, we've been targeting a submission to the FDA in the first half of 2026. initially we've been targeting a submission to the fda in the first half of 2026 On our fourth quarter earnings call, we said that would be in the first quarter. on our fourth quarter earnings call we said that would be in the first quarter Then at a recent conference, I won't mention the name, we had confirmed we actually already have submitted to the FDA. then at a recent conference i won't mention the name we had confirmed we actually already have submitted to the fda Post the data being available, the FDA had included us in the RTOR program, the Real-Time Oncology Review program, and then more recently assigned Breakthrough Therapy designation for zanidatamab in first-line GEA as well. post the data being available the fda had included us in the rtor program the real-time oncology review program and then more recently assigned breakthrough therapy designation for zanidatamab in first-line gea as well We're optimistic that we'll receive a priority review and look forward to approval and then launch of the product later this year. On corporate development side, we're really well-positioned, I think, understanding the substrate that's out there in rare diseases of interest to us and with great financial resources to be able to act $2.5 billion roughly in cash and investments, strong ability to leverage if we need it for attractive opportunities and additional focus that we've placed on corporate development with the hiring of a Chief Business Officer, Tom Riga, dedicating additional management time and focus to those efforts. Confident we'll be able to find really good opportunities for us to deploy capital, improve outcomes for patients, and drive greater returns for shareholders as well. We're optimistic that we'll receive a priority review and look forward to approval and then launch of the product later this year. we're optimistic that we'll receive a priority review and look forward to approval and then launch of the product later this year On corporate development side, we're really well-positioned, I think, understanding the substrate that's out there in rare diseases of interest to us and with great financial resources to be able to act $2.5 billion roughly in cash and investments, strong ability to leverage if we need it for attractive opportunities and additional focus that we've placed on corporate development with the hiring of a Chief Business Officer, Tom Riga, dedicating additional management time and focus to those efforts. on corporate development side we're really well-positioned i think understanding the substrate that's out there in rare diseases of interest to us and with great financial resources to be able to act $2.5 billion roughly in cash and investments strong ability to leverage if we need it for attractive opportunities and additional focus that we've placed on corporate development with the hiring of a chief business officer tom riga dedicating additional management time and focus to those efforts Confident we'll be able to find really good opportunities for us to deploy capital, improve outcomes for patients, and drive greater returns for shareholders as well. confident we'll be able to find really good opportunities for us to deploy capital improve outcomes for patients and drive greater returns for shareholders as well

Speaker 1: Great. Thank you for that, Phil. Maybe just internally, when you think about investments. In the business, obviously, sleep franchise, epilepsy franchise, huge components of the company today. You have this growing oncology business with Ziihera hopefully continuing to grow as we get more and more clinical updates. How are you thinking about sort of resourcing CNS relative to oncology just internally in how you kind of think about that business over the next couple of years? Great. great Thank you for that, Phil. thank you for that phil Maybe just internally, when you think about investments. maybe just internally when you think about investments In the business, obviously, sleep franchise, epilepsy franchise, huge components of the company today. in the business obviously sleep franchise epilepsy franchise huge components of the company today You have this growing oncology business with Ziihera hopefully continuing to grow as we get more and more clinical updates. you have this growing oncology business with ziihera hopefully continuing to grow as we get more and more clinical updates How are you thinking about sort of resourcing CNS relative to oncology just internally in how you kind of think about that business over the next couple of years? how are you thinking about sort of resourcing cns relative to oncology just internally in how you kind of think about that business over the next couple of years

Speaker 2: Yeah. We've got great opportunities sort of in that non-sleep portion of our business. As part of the guidance, we did say that revenue, which is over half of the company's total revenue in 2025, we expect to grow double digits here in 2026, continued growth of Epidiolex, and then obviously ramping for Modeyso and growth in Ziihera as well. We are extremely focused in terms of capital allocation on investing behind the existing marketed products and making sure that we're getting those to patients who can benefit from them and driving revenue there. That is what pays the bills and gives us the resources to invest. Secondarily, really making sure that we're investing behind the existing pipeline that's in-house now. We've got some great opportunities, first and foremost, probably to build out indications for Ziihera. Yeah. yeah We've got great opportunities sort of in that non-sleep portion of our business. we've got great opportunities sort of in that non-sleep portion of our business As part of the guidance, we did say that revenue, which is over half of the company's total revenue in 2025, we expect to grow double digits here in 2026, continued growth of Epidiolex, and then obviously ramping for Modeyso and growth in Ziihera as well. as part of the guidance we did say that revenue which is over half of the company's total revenue in 2025 we expect to grow double digits here in 2026 continued growth of epidiolex and then obviously ramping for modeyso and growth in ziihera as well We are extremely focused in terms of capital allocation on investing behind the existing marketed products and making sure that we're getting those to patients who can benefit from them and driving revenue there. we are extremely focused in terms of capital allocation on investing behind the existing marketed products and making sure that we're getting those to patients who can benefit from them and driving revenue there That is what pays the bills and gives us the resources to invest. that is what pays the bills and gives us the resources to invest Secondarily, really making sure that we're investing behind the existing pipeline that's in-house now. secondarily really making sure that we're investing behind the existing pipeline that's in-house now We've got some great opportunities, first and foremost, probably to build out indications for Ziihera. we've got some great opportunities first and foremost probably to build out indications for ziihera Certainly a high priority, as I mentioned earlier, for us to go ahead and increase the company's future growth profile through additional corp dev. As we think about the areas where we're currently operating in, sleep, epilepsy, and oncology, as you look at the substrate there is the most interesting innovative science, probably in the epilepsy space and in the oncology space. In sleep, which I'm sure we'll talk about going forward. Orexins are currently the only sort of real innovation coming forward. That may change over time, and we'll continue to look for opportunities to grow that franchise as well. Definitely beyond the areas that we're currently in, we see some really good opportunities in rare disease to go ahead and expand our presence, use our capabilities, to drive great outcomes for patients as well as for investors there as well. Certainly a high priority, as I mentioned earlier, for us to go ahead and increase the company's future growth profile through additional corp dev. certainly a high priority as i mentioned earlier for us to go ahead and increase the company's future growth profile through additional corp dev As we think about the areas where we're currently operating in, sleep, epilepsy, and oncology, as you look at the substrate there is the most interesting innovative science, probably in the epilepsy space and in the oncology space. In sleep, which I'm sure we'll talk about going forward. as we think about the areas where we're currently operating in sleep epilepsy and oncology as you look at the substrate there is the most interesting innovative science probably in the epilepsy space and in the oncology space. in sleep which i'm sure we'll talk about going forward Orexins are currently the only sort of real innovation coming forward. orexins are currently the only sort of real innovation coming forward That may change over time, and we'll continue to look for opportunities to grow that franchise as well. that may change over time and we'll continue to look for opportunities to grow that franchise as well Definitely beyond the areas that we're currently in, we see some really good opportunities in rare disease to go ahead and expand our presence, use our capabilities, to drive great outcomes for patients as well as for investors there as well. definitely beyond the areas that we're currently in we see some really good opportunities in rare disease to go ahead and expand our presence use our capabilities to drive great outcomes for patients as well as for investors there as well We haven't yet done that, so I know we've been saying this for a few years, but I wouldn't be surprised if in the coming quarters or years you're seeing us expand into one or more new rare disease areas beyond those that we're currently in. We haven't yet done that, so I know we've been saying this for a few years, but I wouldn't be surprised if in the coming quarters or years you're seeing us expand into one or more new rare disease areas beyond those that we're currently in. we haven't yet done that so i know we've been saying this for a few years but i wouldn't be surprised if in the coming quarters or years you're seeing us expand into one or more new rare disease areas beyond those that we're currently in

Speaker 1: Yeah. People, we tend to have short memories, so we think about the Modeyso transaction as sort of being a recent one. Just maybe looking forward, is that maybe a framework in terms of what we could see from Jazz and just in terms of sort of the deal type, deal size? Yeah. yeah People, we tend to have short memories, so we think about the Modeyso transaction as sort of being a recent one. people we tend to have short memories so we think about the modeyso transaction as sort of being a recent one Just maybe looking forward, is that maybe a framework in terms of what we could see from Jazz and just in terms of sort of the deal type, deal size? just maybe looking forward is that maybe a framework in terms of what we could see from jazz and just in terms of sort of the deal type deal size

Speaker 2: Yeah. Definitely would love if we could find some more Chimerix's to acquire. I would say that if you think about where we'll be investing, in the areas we've got existing deep expertise, knowledge, and relationships, we'll invest across that full spectrum from marketed products all the way to preclinical. The Saniona licensing deal that we did last year in the epilepsy space is an example of that. If we're going into new areas of rare disease, which I mentioned I expect that we will do going forward, those initial investments would likely be targeted to things that are post proof of concept or at least proof of mechanism with an improved compound going after that mechanism. As we build that expertise, knowledge, and relationships, begin to invest earlier in clinical or even preclinical development. Yeah. yeah Definitely would love if we could find some more Chimerix's to acquire. definitely would love if we could find some more chimerix's to acquire I would say that if you think about where we'll be investing, in the areas we've got existing deep expertise, knowledge, and relationships, we'll invest across that full spectrum from marketed products all the way to preclinical. i would say that if you think about where we'll be investing in the areas we've got existing deep expertise knowledge and relationships we'll invest across that full spectrum from marketed products all the way to preclinical The Saniona licensing deal that we did last year in the epilepsy space is an example of that. the saniona licensing deal that we did last year in the epilepsy space is an example of that If we're going into new areas of rare disease, which I mentioned I expect that we will do going forward, those initial investments would likely be targeted to things that are post proof of concept or at least proof of mechanism with an improved compound going after that mechanism. if we're going into new areas of rare disease which i mentioned i expect that we will do going forward those initial investments would likely be targeted to things that are post proof of concept or at least proof of mechanism with an improved compound going after that mechanism As we build that expertise, knowledge, and relationships, begin to invest earlier in clinical or even preclinical development. as we build that expertise knowledge and relationships begin to invest earlier in clinical or even preclinical development

Speaker 1: Great. Maybe onto the sleep franchise and obviously Xywav, a great performance the last couple of years. You know, we have Lumryz, other generic oxybates potentially coming online as well, orexin agonists being talked about. Sort of your view on the durability, if you will, of the sleep franchise. Great. great Maybe onto the sleep franchise and obviously Xywav, a great performance the last couple of years. maybe onto the sleep franchise and obviously xywav a great performance the last couple of years You know, we have Lumryz, other generic oxybates potentially coming online as well, orexin agonists being talked about. you know we have lumryz other generic oxybates potentially coming online as well orexin agonists being talked about Sort of your view on the durability, if you will, of the sleep franchise. sort of your view on the durability if you will of the sleep franchise

Speaker 2: Yeah. We're really pleased over the years with how Xywav has performed, not only in building out the idiopathic hypersomnia indication, where we're the only approved drug, and I think have been quite successful in building awareness of the utility of an oxybate for patients with idiopathic hypersomnia, but honestly also in narcolepsy as well, where I think many on the street, potentially even some internally, expected something different to happen than what really happened. You know, we've been continuing to build quarter after quarter the number of patients on Xywav with narcolepsy, even with the emergence of a branded competitor and the AG. Yeah. yeah We're really pleased over the years with how Xywav has performed, not only in building out the idiopathic hypersomnia indication, where we're the only approved drug, and I think have been quite successful in building awareness of the utility of an oxybate for patients with idiopathic hypersomnia, but honestly also in narcolepsy as well, where I think many on the street, potentially even some internally, expected something different to happen than what really happened. we're really pleased over the years with how xywav has performed not only in building out the idiopathic hypersomnia indication where we're the only approved drug and i think have been quite successful in building awareness of the utility of an oxybate for patients with idiopathic hypersomnia but honestly also in narcolepsy as well where i think many on the street potentially even some internally expected something different to happen than what really happened You know, we've been continuing to build quarter after quarter the number of patients on Xywav with narcolepsy, even with the emergence of a branded competitor and the AG. you know we've been continuing to build quarter after quarter the number of patients on xywav with narcolepsy even with the emergence of a branded competitor and the ag It had, I think, even more net patient adds in the fourth quarter than the branded competitor did. I think it speaks to the unique benefit that Xywav offers, which is a safety benefit of having low sodium used in the patient population, whether that's those with narcolepsy or idiopathic hypersomnia, that have a two to three times higher incidence of and risk for cardiovascular events. We've got data that shows, for example, if you go from a high sodium oxybate to a low sodium oxybate, you see clinically meaningful reductions in blood pressure. This kind of benefit we think is resonating with physicians and patients. It's part of the reason why we're not only building the market in idiopathic hypersomnia, but having probably more durability in narcolepsy than many would have thought. It had, I think, even more net patient adds in the fourth quarter than the branded competitor did. it had i think even more net patient adds in the fourth quarter than the branded competitor did I think it speaks to the unique benefit that Xywav offers, which is a safety benefit of having low sodium used in the patient population, whether that's those with narcolepsy or idiopathic hypersomnia, that have a two to three times higher incidence of and risk for cardiovascular events. i think it speaks to the unique benefit that xywav offers which is a safety benefit of having low sodium used in the patient population whether that's those with narcolepsy or idiopathic hypersomnia that have a two to three times higher incidence of and risk for cardiovascular events We've got data that shows, for example, if you go from a high sodium oxybate to a low sodium oxybate, you see clinically meaningful reductions in blood pressure. we've got data that shows for example if you go from a high sodium oxybate to a low sodium oxybate you see clinically meaningful reductions in blood pressure This kind of benefit we think is resonating with physicians and patients. this kind of benefit we think is resonating with physicians and patients It's part of the reason why we're not only building the market in idiopathic hypersomnia, but having probably more durability in narcolepsy than many would have thought. it's part of the reason why we're not only building the market in idiopathic hypersomnia but having probably more durability in narcolepsy than many would have thought I mentioned on our fourth quarter call, there were some accounts last year that had a step through the AG before you could get to one of the branded options, and we still had the highest share there. This benefit, which is a safety benefit, does resonate with physicians, with patients, and we'd expect to resonate with many payers as well. I mentioned on our fourth quarter call, there were some accounts last year that had a step through the AG before you could get to one of the branded options, and we still had the highest share there. i mentioned on our fourth quarter call there were some accounts last year that had a step through the ag before you could get to one of the branded options and we still had the highest share there This benefit, which is a safety benefit, does resonate with physicians, with patients, and we'd expect to resonate with many payers as well. this benefit which is a safety benefit does resonate with physicians with patients and we'd expect to resonate with many payers as well

Speaker 1: Great. You know, we've had conversations with different KOLs, and their views on orexin agonists in general seems to be varied. In your conversations with key opinion leaders around the potential impact of orexin agonists, what are you hearing from them about what that impact could be on the Great. great You know, we've had conversations with different KOLs, and their views on orexin agonists in general seems to be varied. you know we've had conversations with different kols and their views on orexin agonists in general seems to be varied In your conversations with key opinion leaders around the potential impact of orexin agonists, what are you hearing from them about what that impact could be on the in your conversations with key opinion leaders around the potential impact of orexin agonists what are you hearing from them about what that impact could be on the

Speaker 2: There's a great excitement for the orexins, not only in hypersomnias where we're operating, but potentially in patients with ADHD or Alzheimer's, Parkinson's, et cetera. We don't follow that portion of it as much, so I'll limit my comments maybe to talking about the role in hypersomnias. Certainly, orexins appear to be the most potent wake-promoting agents that we've seen to date, particularly in narcolepsy type 1 patients, which is where we'd expect to see the first application and approval of Takeda's product, potentially getting approved and launched yet this year. I think the role in NT2, the role in IH, is still to be played out and still uncertain. There's a great excitement for the orexins, not only in hypersomnias where we're operating, but potentially in patients with ADHD or Alzheimer's, Parkinson's, et cetera. there's a great excitement for the orexins not only in hypersomnias where we're operating but potentially in patients with adhd or alzheimer's parkinson's et cetera We don't follow that portion of it as much, so I'll limit my comments maybe to talking about the role in hypersomnias. we don't follow that portion of it as much so i'll limit my comments maybe to talking about the role in hypersomnias Certainly, orexins appear to be the most potent wake-promoting agents that we've seen to date, particularly in narcolepsy type 1 patients, which is where we'd expect to see the first application and approval of Takeda's product, potentially getting approved and launched yet this year. certainly orexins appear to be the most potent wake-promoting agents that we've seen to date particularly in narcolepsy type 1 patients which is where we'd expect to see the first application and approval of takeda's product potentially getting approved and launched yet this year I think the role in NT2, the role in IH, is still to be played out and still uncertain. i think the role in nt2 the role in ih is still to be played out and still uncertain You know, Jazz for quite a number of years has been saying that we viewed orexins and oxybate as being complementary and expected there to be concomitant use, not that orexins would actually cure patients and obviate the need for oxybate. I think for many years, people looked at that as a maybe Jazz self-serving comment. There was hope, I think, that these orexin products might go ahead and be the cure, if you will, functional cure for patients with narcolepsy, particularly narcolepsy type 1. That does not seem, from our view, to be the way the data is playing out, and I think other, whether it's KOLs or other corporates, I think are also adopting the view that these will be complementary therapies. You know, Jazz for quite a number of years has been saying that we viewed orexins and oxybate as being complementary and expected there to be concomitant use, not that orexins would actually cure patients and obviate the need for oxybate. you know jazz for quite a number of years has been saying that we viewed orexins and oxybate as being complementary and expected there to be concomitant use not that orexins would actually cure patients and obviate the need for oxybate I think for many years, people looked at that as a maybe Jazz self-serving comment. i think for many years people looked at that as a maybe jazz self-serving comment There was hope, I think, that these orexin products might go ahead and be the cure, if you will, functional cure for patients with narcolepsy, particularly narcolepsy type 1. there was hope i think that these orexin products might go ahead and be the cure if you will functional cure for patients with narcolepsy particularly narcolepsy type 1 That does not seem, from our view, to be the way the data is playing out, and I think other, whether it's KOLs or other corporates, I think are also adopting the view that these will be complementary therapies. that does not seem from our view to be the way the data is playing out and i think other whether it's kols or other corporates i think are also adopting the view that these will be complementary therapies My expectation is that if a company's gonna spend $2 billion to get a company that has an oxybate and they already have an orexin, they're probably not viewing them as being competitive. Either would being complementary. Hopefully good news for patients with narcolepsy that this could be a more effective daytime treatment to use alongside an oxybate to help treat their symptoms and get better outcomes. My expectation is that if a company's gonna spend $2 billion to get a company that has an oxybate and they already have an orexin, they're probably not viewing them as being competitive. my expectation is that if a company's gonna spend $2 billion to get a company that has an oxybate and they already have an orexin they're probably not viewing them as being competitive Either would being complementary. either would being complementary Hopefully good news for patients with narcolepsy that this could be a more effective daytime treatment to use alongside an oxybate to help treat their symptoms and get better outcomes. hopefully good news for patients with narcolepsy that this could be a more effective daytime treatment to use alongside an oxybate to help treat their symptoms and get better outcomes

Speaker 1: Great. Maybe a couple of questions on epilepsy. You know, Epidiolex settlement looks to have a really nice IP runway. When you think about sort of maybe the growth profile or the growth outlook for Epidiolex, how are you thinking about that? Great. great Maybe a couple of questions on epilepsy. maybe a couple of questions on epilepsy You know, Epidiolex settlement looks to have a really nice IP runway. you know epidiolex settlement looks to have a really nice ip runway When you think about sort of maybe the growth profile or the growth outlook for Epidiolex, how are you thinking about that? when you think about sort of maybe the growth profile or the growth outlook for epidiolex how are you thinking about that

Speaker 2: Yeah. Really pleased to have had the ANDA settlements with the 10 ANDA filers that we announced last year in the early part of the year, giving us runway out to the very late 2030s. And the product last year grew nicely past that billion-dollar mark, and we see opportunities for continued growth of Epidiolex going forward. A number of places where we're focused, one I would highlight is in the adult patient population. Many of these are in long-term care settings. We've been expanding our outreach efforts there. Many of these patients also have LGS, a condition that takes over a dozen years often to be diagnosed, so we've helped with the REST-LGS tool to help physicians identify these patients. At times, there can be difficulties as someone goes onto therapy of getting up to and titrating to an efficacious dose and then staying on therapy. Yeah. yeah Really pleased to have had the ANDA settlements with the 10 ANDA filers that we announced last year in the early part of the year, giving us runway out to the very late 2030s. really pleased to have had the anda settlements with the 10 anda filers that we announced last year in the early part of the year giving us runway out to the very late 2030s And the product last year grew nicely past that billion-dollar mark, and we see opportunities for continued growth of Epidiolex going forward. and the product last year grew nicely past that billion-dollar mark and we see opportunities for continued growth of epidiolex going forward A number of places where we're focused, one I would highlight is in the adult patient population. a number of places where we're focused one i would highlight is in the adult patient population Many of these are in long-term care settings. many of these are in long-term care settings We've been expanding our outreach efforts there. we've been expanding our outreach efforts there Many of these patients also have LGS, a condition that takes over a dozen years often to be diagnosed, so we've helped with the REST-LGS tool to help physicians identify these patients. many of these patients also have lgs a condition that takes over a dozen years often to be diagnosed so we've helped with the rest-lgs tool to help physicians identify these patients At times, there can be difficulties as someone goes onto therapy of getting up to and titrating to an efficacious dose and then staying on therapy. at times there can be difficulties as someone goes onto therapy of getting up to and titrating to an efficacious dose and then staying on therapy They're really effective Nurse Navigator program that's been rolled out to a minority of patients so far that we're looking to expand because we do see better experiences on product, including greater persistency, when they're having that additional support. We're also looking for ways to improve the product profile for those adult patients. We're working on a formulation that could make the product more attractive to adult patients and looking for additional ways that we can generate data to inform clinicians on uses of Epidiolex, including the phase one study that we recently mentioned. We're starting focal onset seizures as well. Beyond Epidiolex itself, with that long runway to the very late 2030s, this certainly is a franchise we'd like to build out with additional products, to have in the bag and build on our existing relationships, to benefit patients. They're really effective Nurse Navigator program that's been rolled out to a minority of patients so far that we're looking to expand because we do see better experiences on product, including greater persistency, when they're having that additional support. they're really effective nurse navigator program that's been rolled out to a minority of patients so far that we're looking to expand because we do see better experiences on product including greater persistency when they're having that additional support We're also looking for ways to improve the product profile for those adult patients. we're also looking for ways to improve the product profile for those adult patients We're working on a formulation that could make the product more attractive to adult patients and looking for additional ways that we can generate data to inform clinicians on uses of Epidiolex, including the phase one study that we recently mentioned. we're working on a formulation that could make the product more attractive to adult patients and looking for additional ways that we can generate data to inform clinicians on uses of epidiolex including the phase one study that we recently mentioned We're starting focal onset seizures as well. we're starting focal onset seizures as well Beyond Epidiolex itself, with that long runway to the very late 2030s, this certainly is a franchise we'd like to build out with additional products, to have in the bag and build on our existing relationships, to benefit patients. beyond epidiolex itself with that long runway to the very late 2030s this certainly is a franchise we'd like to build out with additional products to have in the bag and build on our existing relationships to benefit patients

Speaker 1: How much of the safety tolerability observed with Epidiolex, how much of a differentiator is that in epilepsy? How much of the safety tolerability observed with Epidiolex, how much of a differentiator is that in epilepsy? how much of the safety tolerability observed with epidiolex how much of a differentiator is that in epilepsy

Speaker 2: You know, most of these patients are on polypharmacy. They're typically taking three or more anti-seizure medications, and Epidiolex seems to combine very well and is often one of those medications that they're on. You even see this in some of the newer products coming through clinical development, where in a number of these cases you've had probably a third or more of patients that have been on Epidiolex in those studies as well. We do expect going forward there'll be additional innovative therapies that will help improve patients' reductions in seizures, but there will be a continued need for additional add-on therapies, and Epidiolex is well-positioned to be one of those. You know, most of these patients are on polypharmacy. you know most of these patients are on polypharmacy They're typically taking three or more anti-seizure medications, and Epidiolex seems to combine very well and is often one of those medications that they're on. they're typically taking three or more anti-seizure medications and epidiolex seems to combine very well and is often one of those medications that they're on You even see this in some of the newer products coming through clinical development, where in a number of these cases you've had probably a third or more of patients that have been on Epidiolex in those studies as well. you even see this in some of the newer products coming through clinical development where in a number of these cases you've had probably a third or more of patients that have been on epidiolex in those studies as well We do expect going forward there'll be additional innovative therapies that will help improve patients' reductions in seizures, but there will be a continued need for additional add-on therapies, and Epidiolex is well-positioned to be one of those. we do expect going forward there'll be additional innovative therapies that will help improve patients' reductions in seizures but there will be a continued need for additional add-on therapies and epidiolex is well-positioned to be one of those

Speaker 1: Right. Maybe a few questions on the oncology franchise. Let me first maybe lay out so you know, so seeing a sort of encouraging launch, maybe you can kind of speak to that, you know, what's sort of driving that and maybe how you see that evolving in the next few years. Right. right Maybe a few questions on the oncology franchise. maybe a few questions on the oncology franchise Let me first maybe lay out so you know, so seeing a sort of encouraging launch, maybe you can kind of speak to that, you know, what's sort of driving that and maybe how you see that evolving in the next few years. let me first maybe lay out so you know so seeing a sort of encouraging launch maybe you can kind of speak to that you know what's sort of driving that and maybe how you see that evolving in the next few years

Speaker 2: Yeah. We've been really pleased with the uptake of Modeyso. There's really been nothing for these patients since the advent of radiotherapy 60 years ago. We saw strong initial conversion of patients that were on the expanded access program. Of the 360+ patients treated in 2025, the vast majority of those were new patients. Really pleased with that adoption and uptake, including in those new patients, not just the conversion from the EAP program. This is a product we said we see having $500 million peak sales potential just here in the U.S. This early uptake is very encouraging. We're still reserving judgment on whether that $500 million should change or not.. Yeah. yeah We've been really pleased with the uptake of Modeyso. we've been really pleased with the uptake of modeyso There's really been nothing for these patients since the advent of radiotherapy 60 years ago. there's really been nothing for these patients since the advent of radiotherapy 60 years ago We saw strong initial conversion of patients that were on the expanded access program. we saw strong initial conversion of patients that were on the expanded access program Of the 360+ patients treated in 2025, the vast majority of those were new patients. of the 360+ patients treated in 2025 the vast majority of those were new patients Really pleased with that adoption and uptake, including in those new patients, not just the conversion from the EAP program. really pleased with that adoption and uptake including in those new patients not just the conversion from the eap program This is a product we said we see having $500 million peak sales potential just here in the U.S. this is a product we said we see having $500 million peak sales potential just here in the u.s This early uptake is very encouraging. this early uptake is very encouraging We're still reserving judgment on whether that $500 million should change or not. . we're still reserving judgment on whether that $500 million should change or not I'll be monitoring two things over time to understand if that should be moved up. One is, do we get the epi right? Roughly 2,000 patients. Are there actually more out there that can benefit from Modeyso? And then secondarily, duration of treatment. We've been on the market since mid-August, so it's still early to know how long patients will stay on. You know, our first patients will get out to a year, obviously, therefore are going to be those that would have been out in August of this year. So by end of this year, I think we'll have a much better view on average duration of treatment, not just median, and be able to understand does that also influence the peak sales potential. I'll be monitoring two things over time to understand if that should be moved up. i'll be monitoring two things over time to understand if that should be moved up One is, do we get the epi right? one is do we get the epi right Roughly 2,000 patients. roughly 2,000 patients Are there actually more out there that can benefit from Modeyso? are there actually more out there that can benefit from modeyso And then secondarily, duration of treatment. and then secondarily duration of treatment We've been on the market since mid-August, so it's still early to know how long patients will stay on. we've been on the market since mid-august so it's still early to know how long patients will stay on You know, our first patients will get out to a year, obviously, therefore are going to be those that would have been out in August of this year. you know our first patients will get out to a year obviously therefore are going to be those that would have been out in august of this year So by end of this year, I think we'll have a much better view on average duration of treatment, not just median, and be able to understand does that also influence the peak sales potential. so by end of this year i think we'll have a much better view on average duration of treatment not just median and be able to understand does that also influence the peak sales potential

Speaker 1: Yeah, maybe you could comment on how much, how important is that frontline update on sort of that $500 million peak number in the U.S. I guess maybe how we should think about it. Could it be potentially more? Yeah, maybe you could comment on how much, how important is that frontline update on sort of that $500 million peak number in the U.S. yeah maybe you could comment on how much how important is that frontline update on sort of that $500 million peak number in the u.s I guess maybe how we should think about it. i guess maybe how we should think about it Could it be potentially more? could it be potentially more

Speaker 2: Yeah. No, great question. The first-line use was included in that $500 million estimate when we had provided it. When we acquired Chimerix, we did make some adjustments to the ACTION study. We increased the number of patients by about 100. We changed the primary endpoint to be overall survival that we think is more appropriate, and that readout is expected in late this year or early in 2027, so look forward to that readout as well. We are approved in that recurrent setting. That's where we promote to, but we do know that given the unmet need there and the physicians see this as a very well-tolerated drug, that some of that early uptake is occurring in physicians using this in earlier line patients and first-line patients. Yeah. yeah No, great question. no great question The first-line use was included in that $500 million estimate when we had provided it. the first-line use was included in that $500 million estimate when we had provided it When we acquired Chimerix, we did make some adjustments to the ACTION study. when we acquired chimerix we did make some adjustments to the action study We increased the number of patients by about 100. we increased the number of patients by about 100 We changed the primary endpoint to be overall survival that we think is more appropriate, and that readout is expected in late this year or early in 2027, so look forward to that readout as well. we changed the primary endpoint to be overall survival that we think is more appropriate and that readout is expected in late this year or early in 2027 so look forward to that readout as well We are approved in that recurrent setting. we are approved in that recurrent setting That's where we promote to, but we do know that given the unmet need there and the physicians see this as a very well-tolerated drug, that some of that early uptake is occurring in physicians using this in earlier line patients and first-line patients. that's where we promote to but we do know that given the unmet need there and the physicians see this as a very well-tolerated drug that some of that early uptake is occurring in physicians using this in earlier line patients and first-line patients

Speaker 1: Great. With, you know, we talked about the HERIZON update in gastric cancer readout, so great results. How are you preparing for that launch and that front line population? Again, extending that beyond, I guess you also have to kind of think ahead and potentially breast coming on in a couple of years. How are you thinking about that initial launch? Then how are you setting up hopefully for success beyond gastric? Great. great With, you know, we talked about the HERIZON update in gastric cancer readout, so great results. with you know we talked about the herizon update in gastric cancer readout so great results How are you preparing for that launch and that front line population? how are you preparing for that launch and that front line population Again, extending that beyond, I guess you also have to kind of think ahead and potentially breast coming on in a couple of years. again extending that beyond i guess you also have to kind of think ahead and potentially breast coming on in a couple of years How are you thinking about that initial launch? how are you thinking about that initial launch Then how are you setting up hopefully for success beyond gastric? then how are you setting up hopefully for success beyond gastric

Speaker 2: Yeah. Really excited to be bringing this to market in the not-too-distant future, given the kind of practice-changing results that we generated. The current indication is in second-line biliary tract cancer, and these are effectively the same physicians. Probably there's 90%+ overlap of the prescribing physicians for first-line GEA. These physicians are getting initial experience with the drug in those BTC patients. We think that initial experience will be very helpful as we come to market later this year. In first line GEA, then yes, the thing sort of up would be breast cancer. There we're studying metastatic breast cancer, basically in patients who have progressed after an HER2 therapy or intolerance to an HER2 therapy. Really the first one into generating data in that space, which right now is sort of a third line plus. Yeah. yeah Really excited to be bringing this to market in the not-too-distant future, given the kind of practice-changing results that we generated. really excited to be bringing this to market in the not-too-distant future given the kind of practice-changing results that we generated The current indication is in second-line biliary tract cancer, and these are effectively the same physicians. the current indication is in second-line biliary tract cancer and these are effectively the same physicians Probably there's 90%+ overlap of the prescribing physicians for first-line GEA. probably there's 90%+ overlap of the prescribing physicians for first-line gea These physicians are getting initial experience with the drug in those BTC patients. these physicians are getting initial experience with the drug in those btc patients We think that initial experience will be very helpful as we come to market later this year. In first line GEA, then yes, the thing sort of up would be breast cancer. we think that initial experience will be very helpful as we come to market later this year. in first line gea then yes the thing sort of up would be breast cancer There we're studying metastatic breast cancer, basically in patients who have progressed after an HER2 therapy or intolerance to an HER2 therapy. there we're studying metastatic breast cancer basically in patients who have progressed after an her2 therapy or intolerance to an her2 therapy Really the first one into generating data in that space, which right now is sort of a third line plus. really the first one into generating data in that space which right now is sort of a third line plus With an HER2 moving into the first line, that would become more of a second line plus kind of indication. Enrollment's going quite well. We currently expect enrollment to complete in the first half of 2027, and then trying to use our best estimate on what we're seeing in events rates currently, that would be late 2027 or late 2028 for the initial readout there. That would be the final PFS and then the first interim OS. With an HER2 moving into the first line, that would become more of a second line plus kind of indication. with an her2 moving into the first line that would become more of a second line plus kind of indication Enrollment's going quite well. enrollment's going quite well We currently expect enrollment to complete in the first half of 2027, and then trying to use our best estimate on what we're seeing in events rates currently, that would be late 2027 or late 2028 for the initial readout there. we currently expect enrollment to complete in the first half of 2027 and then trying to use our best estimate on what we're seeing in events rates currently that would be late 2027 or late 2028 for the initial readout there That would be the final PFS and then the first interim OS. that would be the final pfs and then the first interim os

Speaker 1: Right. You know, again, beyond this initial data set with this profile, there are various ways you can go. You can go into earlier-line breast cancer. There's also the tumor-agnostic approach around HER2 therapies. How are you thinking about that beyond the initial indications that you're currently executing on? Right. right You know, again, beyond this initial data set with this profile, there are various ways you can go. you know again beyond this initial data set with this profile there are various ways you can go You can go into earlier-line breast cancer. you can go into earlier-line breast cancer There's also the tumor-agnostic approach around HER2 therapies. there's also the tumor-agnostic approach around her2 therapies How are you thinking about that beyond the initial indications that you're currently executing on? how are you thinking about that beyond the initial indications that you're currently executing on

Speaker 2: We do feel like the data that we generated in that first line GEA study are pretty definitive proof that at least in that setting, we have a vastly superior targeted HER2 agent compared to Herceptin. Clearly we're looking where Herceptin was approved and successful, which is breast cancer and gastric cancer, looking for ways to expand there. That could be both early breast cancer, like you mentioned, adjuvant, neoadjuvant, also early gastric. Then we're looking at some places where maybe Herceptin didn't get approved, didn't quite meet the bar, but with a much more potent HER2 agent, we could have success. We're looking in non-small cell lung cancer. We have some really outstanding early results in colorectal as well that we're looking at. We do feel like the data that we generated in that first line GEA study are pretty definitive proof that at least in that setting, we have a vastly superior targeted HER2 agent compared to Herceptin. we do feel like the data that we generated in that first line gea study are pretty definitive proof that at least in that setting we have a vastly superior targeted her2 agent compared to herceptin Clearly we're looking where Herceptin was approved and successful, which is breast cancer and gastric cancer, looking for ways to expand there. clearly we're looking where herceptin was approved and successful which is breast cancer and gastric cancer looking for ways to expand there That could be both early breast cancer, like you mentioned, adjuvant, neoadjuvant, also early gastric. that could be both early breast cancer like you mentioned adjuvant neoadjuvant also early gastric Then we're looking at some places where maybe Herceptin didn't get approved, didn't quite meet the bar, but with a much more potent HER2 agent, we could have success. then we're looking at some places where maybe herceptin didn't get approved didn't quite meet the bar but with a much more potent her2 agent we could have success We're looking in non-small cell lung cancer. we're looking in non-small cell lung cancer We have some really outstanding early results in colorectal as well that we're looking at. we have some really outstanding early results in colorectal as well that we're looking at Even within the existing areas that we're in, trying to figure out what are ways that we can go ahead and improve the data that's available for physicians over time to inform use. Striking up partnerships with companies that have, you know, novel, could be best in class, HER2-targeted TKIs, for example, in breast cancer. We've got a recently announced collaboration with Boehringer Ingelheim, zongertinib, and then you'll probably expect to see more of that from us over time as we build out zani. There's the ongoing pan-tumor trial that you had mentioned that could also lead to an additional indications. That's a registrational quality and size study as well. Even within the existing areas that we're in, trying to figure out what are ways that we can go ahead and improve the data that's available for physicians over time to inform use. even within the existing areas that we're in trying to figure out what are ways that we can go ahead and improve the data that's available for physicians over time to inform use Striking up partnerships with companies that have, you know, novel, could be best in class, HER2-targeted TKIs, for example, in breast cancer. striking up partnerships with companies that have you know novel could be best in class her2-targeted tkis for example in breast cancer We've got a recently announced collaboration with Boehringer Ingelheim, zongertinib, and then you'll probably expect to see more of that from us over time as we build out zani. we've got a recently announced collaboration with boehringer ingelheim zongertinib and then you'll probably expect to see more of that from us over time as we build out zani There's the ongoing pan-tumor trial that you had mentioned that could also lead to an additional indications. there's the ongoing pan-tumor trial that you had mentioned that could also lead to an additional indications That's a registrational quality and size study as well. that's a registrational quality and size study as well

Speaker 1: Within oncology, there's other areas as well. You mentioned the frontline maintenance small cell lung cancer study. When you think about again, optionality around the oncology portfolio and in the pipeline, how should we think about sort of the rest of the oncology business for Jazz? Within oncology, there's other areas as well. within oncology there's other areas as well You mentioned the frontline maintenance small cell lung cancer study. you mentioned the frontline maintenance small cell lung cancer study When you think about again, optionality around the oncology portfolio and in the pipeline, how should we think about sort of the rest of the oncology business for Jazz? when you think about again optionality around the oncology portfolio and in the pipeline how should we think about sort of the rest of the oncology business for jazz

Speaker 2: Yeah. With Zepzelca, that first-line maintenance setting in combination with atezolizumab, really excited about those results. Strong overall survival benefit and very clinically meaningful benefit there. We would expect to see that become standard of care in that first-line maintenance setting. As far as how the overall product revenue progresses, that will depend on the dynamics in the current second line, which is the majority of use, where there is a competitor that has overall survival benefit that we would expect to become standard of care over time and our use in second line decline. And also, there's not data that we would point to that would indicate that we expect if you're getting Zepzelca in that first line maintenance setting, that you'd be rechallenged in second line. Yeah. yeah With Zepzelca, that first-line maintenance setting in combination with atezolizumab, really excited about those results. with zepzelca that first-line maintenance setting in combination with atezolizumab really excited about those results Strong overall survival benefit and very clinically meaningful benefit there. strong overall survival benefit and very clinically meaningful benefit there We would expect to see that become standard of care in that first-line maintenance setting. we would expect to see that become standard of care in that first-line maintenance setting As far as how the overall product revenue progresses, that will depend on the dynamics in the current second line, which is the majority of use, where there is a competitor that has overall survival benefit that we would expect to become standard of care over time and our use in second line decline. as far as how the overall product revenue progresses that will depend on the dynamics in the current second line which is the majority of use where there is a competitor that has overall survival benefit that we would expect to become standard of care over time and our use in second line decline And also, there's not data that we would point to that would indicate that we expect if you're getting Zepzelca in that first line maintenance setting, that you'd be rechallenged in second line. and also there's not data that we would point to that would indicate that we expect if you're getting zepzelca in that first line maintenance setting that you'd be rechallenged in second line Again, really pleased with the benefit we can bring for patients in that first line maintenance setting. That's where we've been focused for quite some time. We'll continue to be focused there, but recognize that that second line business will decline over time. Again, really pleased with the benefit we can bring for patients in that first line maintenance setting. again really pleased with the benefit we can bring for patients in that first line maintenance setting That's where we've been focused for quite some time. that's where we've been focused for quite some time We'll continue to be focused there, but recognize that that second line business will decline over time. we'll continue to be focused there but recognize that that second line business will decline over time

Speaker 1: Then earlier on in the pipeline, you have, you know, again, a few different assets across different therapeutic areas of interest, one of which is the KRAS and G12D and NRAS programs. I guess, how are you looking at that space as it evolves and where you think ultimately Jazz could play a role in that space, again, given how much interest there is overall in the RAS space? Then earlier on in the pipeline, you have, you know, again, a few different assets across different therapeutic areas of interest, one of which is the KRAS and G12D and NRAS programs. then earlier on in the pipeline you have you know again a few different assets across different therapeutic areas of interest one of which is the kras and g12d and nras programs I guess, how are you looking at that space as it evolves and where you think ultimately Jazz could play a role in that space, again, given how much interest there is overall in the RAS space? i guess how are you looking at that space as it evolves and where you think ultimately jazz could play a role in that space again given how much interest there is overall in the ras space

Speaker 2: Yeah. We've got a couple of phase I assets ongoing, NRAS that you mentioned, that's sort of in expansion cohorts now. We're pleased we're moving into that. We've got the conditionally activated interferon alpha that's moving into some cohort expansions as well. Pleased that we're sort of passing some of those initial phase I hurdles, moving into those either dose escalation, dose expansion, or cohort expansion studies, and have strong interest in solid tumors for each of those assets. We also, as Jazz has been transitioning over the last six, seven years, into a more fully integrated biopharma company, including not just early development, but actually preclinical development, our own research, we're pleased to have moved our first Jazz-generated asset into the clinic. This is in the epilepsy space. Still holding off on disclosing mechanism of action. Yeah. yeah We've got a couple of phase I assets ongoing, NRAS that you mentioned, that's sort of in expansion cohorts now. we've got a couple of phase i assets ongoing nras that you mentioned that's sort of in expansion cohorts now We're pleased we're moving into that. we're pleased we're moving into that We've got the conditionally activated interferon alpha that's moving into some cohort expansions as well. we've got the conditionally activated interferon alpha that's moving into some cohort expansions as well Pleased that we're sort of passing some of those initial phase I hurdles, moving into those either dose escalation, dose expansion, or cohort expansion studies, and have strong interest in solid tumors for each of those assets. pleased that we're sort of passing some of those initial phase i hurdles moving into those either dose escalation dose expansion or cohort expansion studies and have strong interest in solid tumors for each of those assets We also, as Jazz has been transitioning over the last six, seven years, into a more fully integrated biopharma company, including not just early development, but actually preclinical development, our own research, we're pleased to have moved our first Jazz-generated asset into the clinic. we also as jazz has been transitioning over the last six seven years into a more fully integrated biopharma company including not just early development but actually preclinical development our own research we're pleased to have moved our first jazz-generated asset into the clinic This is in the epilepsy space. this is in the epilepsy space Still holding off on disclosing mechanism of action. still holding off on disclosing mechanism of action We expect to see more assets coming from those efforts as well. While corporate development continued to be the primary source for us of getting new innovation into the company, assets like Ziihera, like Modeyso, we're really pleased. We're beginning to see sort of the fruits of the labor over many years to build the research capability that can generate interesting assets as well. We expect to see more assets coming from those efforts as well. we expect to see more assets coming from those efforts as well While corporate development continued to be the primary source for us of getting new innovation into the company, assets like Ziihera, like Modeyso, we're really pleased. while corporate development continued to be the primary source for us of getting new innovation into the company assets like ziihera like modeyso we're really pleased We're beginning to see sort of the fruits of the labor over many years to build the research capability that can generate interesting assets as well. we're beginning to see sort of the fruits of the labor over many years to build the research capability that can generate interesting assets as well

Speaker 1: Great. You know, we mentioned focal onset seizures as a potential long-term opportunity for Epidiolex. Maybe you know, the basis, if you will, for that is maybe some preliminary data that you've seen internally, maybe pre-clinically, physician feedback on maybe anecdotal evidence. Where what's sort of driving that? Great. great You know, we mentioned focal onset seizures as a potential long-term opportunity for Epidiolex. you know we mentioned focal onset seizures as a potential long-term opportunity for epidiolex Maybe you know, the basis, if you will, for that is maybe some preliminary data that you've seen internally, maybe pre-clinically, physician feedback on maybe anecdotal evidence. maybe you know the basis if you will for that is maybe some preliminary data that you've seen internally maybe pre-clinically physician feedback on maybe anecdotal evidence Where what's sort of driving that? where what's sort of driving that

Speaker 2: That as well as just clinical data you've seen. We're basically in, you know, specific diseases, if you will, as opposed to the seizure type, and we've seen benefits in focal onset. I do think we wanna make sure that we're thinking about how to best direct that development, to be consistent with our focus on rare disease and also the kind of pricing profile that Epidiolex has as well. Trying to find patient population where you've got a significant benefit that you can feel good about both the incremental outcomes that you're driving for patients as well as then the kind of pricing that you have for the product. That as well as just clinical data you've seen. that as well as just clinical data you've seen We're basically in, you know, specific diseases, if you will, as opposed to the seizure type, and we've seen benefits in focal onset. we're basically in you know specific diseases if you will as opposed to the seizure type and we've seen benefits in focal onset I do think we wanna make sure that we're thinking about how to best direct that development, to be consistent with our focus on rare disease and also the kind of pricing profile that Epidiolex has as well. i do think we wanna make sure that we're thinking about how to best direct that development to be consistent with our focus on rare disease and also the kind of pricing profile that epidiolex has as well Trying to find patient population where you've got a significant benefit that you can feel good about both the incremental outcomes that you're driving for patients as well as then the kind of pricing that you have for the product. trying to find patient population where you've got a significant benefit that you can feel good about both the incremental outcomes that you're driving for patients as well as then the kind of pricing that you have for the product

Speaker 1: Great. Bill, John, thank you so much for your time. Enjoy the rest of the conference. Thank you for our listeners, and we'll be back to our next session shortly. Great. great Bill, John, thank you so much for your time. bill john thank you so much for your time Enjoy the rest of the conference. enjoy the rest of the conference Thank you for our listeners, and we'll be back to our next session shortly. thank you for our listeners and we'll be back to our next session shortly

Speaker 2: Thanks, Etzer. Appreciate it. Thanks, Etzer. thanks etzer Appreciate it. appreciate it