Jazz Pharmaceuticals plc

Thank you, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its first quarter 2026 financial results.

The slide presentation accompanying this webcast is available on the Investors section of our website, along with the press release and quarterly report on Form 10-Q for the first quarter ended March 31, 2026. On the call today are Renee Gala, President and Chief Executive Officer; Sam Pearce, Chief Commercial Officer; Robbie Iannone, Global Head of R&D and Chief Medical Officer; and Phil Johnson, Chief Financial Officer.

On Slide 2, I'd like to remind you that today's webcast includes forward-looking statements such as those related to our future financial and operating results, growth potential and anticipated development, regulatory and commercial milestones, which involve risks and uncertainties that could cause actual events, performance, and results to differ materially from those contained in these forward-looking statements. We encourage you to review these risks and uncertainties described in today's press release and under the caption Risk Factors in our annual report on Form 10-K for the fiscal year ended December 31, 2025.

We undertake no duty or obligation to update our forward-looking statements. As noted on Slide 3, we will discuss non-GAAP financial measures on this webcast.

Descriptions of these non-GAAP financial measures and reconciliations of GAAP to non-GAAP financial measures are included in today's press release and the slide presentation available on the Investors section of our website. I'll now turn the call over to Renee.

Thanks, John. Good afternoon, everyone, and thank you for joining today's conference call.

Building on our record year in 2025, we are pleased to share our results from an exceptionally strong first quarter, led by commercial execution across our highly differentiated products for sleep, epilepsies, and cancers. This resulted in our highest ever first quarter total revenues of $1.1 billion, reflecting more than 19% year-over-year growth, driven by the outstanding performance of Xywav, Epidiolex, Modeyso, and Zepzelca.

Our commercial teams generated double-digit growth across all our promoted brands and saw strong contributions from our ongoing launches. This performance reflects the discipline and consistent efforts of our teams working with clarity and purpose to support the physicians and patients we serve.

In addition to our impressive commercial performance to start the year, we are urgently advancing the development of zanidatamab for patients with HER2-positive first-line locally advanced or metastatic GEA where the unmet medical need remains significant. The FDA recently accepted our sBLA for Ziihera under real-time oncology review and granted priority review with a PDUFA date of August 25, 2026.

We are ready to launch Ziihera in GEA as soon as we receive FDA approval, and we expect Ziihera will become the HER2-targeted therapy of choice for HER2-positive first-line GEA patients given the magnitude of benefits seen across both experimental arms when compared to the trastuzumab control arm. In R&D, we continue to make progress across our pipeline with multiple ongoing registrational zanidatamab trials, early-stage trials evaluating oncology assets, and the early development of neuroscience and epilepsy assets.

The year is also off to an excellent operational start with cash flow of over $400 million in the first quarter and non-GAAP adjusted EPS of $6.34. Our financial strength and disciplined capital allocation enable us to invest in the continued growth of our commercial portfolio and pipeline while also positioning us to execute on business development opportunities that fit our strategic focus in rare disease.

With that, I'll turn the call over to Sam to share more details on our commercial performance.

Thank you, Renee. Our commercial team delivered strong results across Jazz's portfolio with momentum from our 2025 launches and coordinated execution continuing into 2026.

I'll begin on Slide 7 with sleep. Xywav's net product sales increased 18% to $408 million in the first quarter of 2026 compared to the same period in 2025.

As expected, HCPs and patients continue to drive demand for safer, low-sodium Xywav, and we saw strong new patient growth with approximately 425 net patient adds. There are now approximately 16,600 active patients taking Xywav, which remains the #1 branded treatment for narcolepsy based on product revenues and the only FDA-approved treatment for idiopathic hypersomnia.

Our field teams continue to expand both the IH and narcolepsy markets by educating HCPs on the importance of addressing the full spectrum of daytime and nighttime symptoms. These efforts are complemented by digital and media campaigns to increase disease awareness and support patient education.

Our Jazz care support services, including field-based nurse educators, support patients from initiation through titration and across the long-term treatment journey. These services remain important differentiators for Jazz.

Moving to Slide 8 and Epidiolex. Epidiolex net product sales increased 15% to $250 million in the first quarter of 2026, driven by strong underlying demand and 16% volume growth during the quarter.

Expanding our reach in the adult patient population and specifically in the long-term care setting remains a key focus and an important near-term growth opportunity. Our Nurse Navigator program continues to have a meaningful impact on improving patient persistency and expanding utilization of this resource remains a priority for 2026.

Finally, as part of our commitment to bring Epidiolex to appropriate patients in Japan, we have partnered with Nippon Zoki, a Japanese company with deep expertise in CNS disorders. Jazz remains the sponsor of the clinical trial, and Nippon Zoki will lead regulatory, distribution, and commercial activities in Japan.

Turning to our oncology portfolio, starting with Ziihera on Slide 9. In the first quarter of 2026, Ziihera generated net product sales of $13 million.

Feedback from biliary tract cancer physicians continues to be positive with real-world experience consistent with the clinical profile observed in our trials. We are also continuing to expand into new community-based accounts beyond academic centers, increasing awareness of Ziihera in BTC and building readiness ahead of a potential launch in GEA.

As a reminder, there is a substantial customer overlap across our solid tumor footprint, including approximately 90% overlap between BTC and GEA accounts. We believe this positions us well to accelerate uptake in GEA following its anticipated approval and launch on or before the August 25 PDUFA date.

Once approved, our existing cross-functional team will be positioned to reach target customers and support rapid adoption of this practice-changing regimen for GEA patients. Turning to Slide 10 and our GEA launch preparations.

Physicians are expressing excitement and interest in the potential use of Ziihera in GEA. It has been more than 15 years since a new first-line HER2-targeted agent became available for patients with metastatic gastric cancer.

Given the unprecedented median overall survival data of more than 2 years, we believe Ziihera has the potential to become the preferred HER2-directed therapy and foundational backbone for treating HER2-positive first-line metastatic GEA. The addition of tislelizumab further improved survival outcomes in both PD-L1 positive and PD-L1 negative patients, consistent with Ziihera's unique mechanism of action that generates an innate immune response in the tumor.

Ziihera already benefits from an established permanent J-code through its FDA approval in second-line HER2-positive BTC, which we expect will simplify reimbursement in GEA and reduce the administrative burden for providers. In addition, the compelling outcomes from the HERIZON-GEA trial supports our expectations for favorable payer access.

Finally, our comprehensive Jazz care support services, together with Ziihera's established availability across customers' preferred distribution channels position us to enable seamless patient access at launch. Turning to Slide 11 and Modeyso.

Modeyso generated $41 million in net product sales in the first quarter of 2026. This strong early performance following its launch in August 2025 reflects the significant unmet need in H3 K27M-mutant diffuse midline glioma, high awareness driven by advocacy groups and the value physicians see for patients.

Approximately 500 patients have been treated with Modeyso since launch through the end of the first quarter. Our highly experienced neuro-oncology field teams, including medical and access colleagues continue to support the launch.

The teams remain focused on expanding reach in community settings, whilst maintaining a well-supported presence in academic centers of excellence. Robust patient-centric support services and payer coverage continue to underpin launch momentum and support appropriate access for patients.

Moving to Slide 12 and Zepzelca. In the first quarter of 2026, Zepzelca net product sales increased 60% to $101 million compared to the same period in 2025.

Growth in the first quarter was primarily driven by strong uptake in the frontline maintenance setting following FDA approval of Zepzelca in combination with Tecentriq in October of last year. Given the strength of the IMforte clinical data and the opportunity to improve both progression-free survival and overall survival for patients with extensive stage small cell lung cancer, health care providers are rapidly adopting the Zepzelca combination in the first-line maintenance setting.

As a result, this new indication is driving the product's strong performance. Our commercial initiatives will continue to be focused on first-line maintenance, reflecting our ongoing commitment to this priority.

For the rest of 2026, first-line maintenance adoption is expected to grow with second-line use decreasing due to competition and fewer Zepzelca naive patients available for treatment. Overall, we are satisfied with the impressive commercial performance achieved across our portfolio in the first quarter and remain focused on maintaining this momentum throughout the year.

With that, I'll now turn the call over to Rob to provide an update on our pipeline. Rob?

Thanks, Sam. I'll start on Slide 14.

This is an exciting time at Jazz. In addition to our outstanding commercial execution, we are also preparing to bring zanidatamab to HER2-positive first-line metastatic GEA patients.

The data from the HERIZON-GEA trial definitively demonstrated that zanidatamab offers improved outcomes on all efficacy measures compared to trastuzumab and should be the new HER2-targeted agent of choice. The data also showed tislelizumab further improved survival outcomes in both PD-L1 positive and PD-L1 negative patients.

The benefit regardless of PD-L1 status may be driven by zanidatamab's unique mechanism of action known as biparatopic binding. This enables zanidatamab to cross-link neighboring HER2 receptors, leading to receptor clustering, which blocks HER2 growth signaling and also triggers the complement cascade.

Zanidatamab's ability to uniquely and broadly activate the innate immune system may in part explain the additional efficacy observed when tislelizumab was added to zanidatamab even in PD-L1 negative tumors. The triplet arm of zanidatamab, tislelizumab, and chemotherapy demonstrated improved overall survival with a remarkable median OS of 26.4 months, representing a meaningful improvement of more than 6 months median OS compared to prior studies in HER2-positive patients who have a poor prognosis in the metastatic setting.

Among patients who had an objective response, the median duration of response was 20.7 months. Again, this benefit was observed irrespective of tumor PD-L1 status.

To put this into context, in the KEYNOTE-811 trial, the duration of response for trastuzumab and pembrolizumab plus chemotherapy was 11.3 months. We are moving quickly to bring zanidatamab to HER2-positive first-line metastatic GEA patients.

Following the oral presentation at ASCO GI in January, we submitted the data for potential inclusion in NCCN guidelines. We're pleased that the manuscript has been accepted for publication by a top-tier medical journal and plan to submit the peer-reviewed manuscript to NCCN once it has been published.

Our supplemental BLA for zanidatamab has received priority review with a PDUFA date of August 25, 2026. We are actively engaged with the FDA in the review process, and we expect potential approval and launch of zanidatamab in GEA on or before the PDUFA date.

Turning to Slide 15 and our pipeline. We have multiple clinical trials across our pipeline from early stage to registrational trials.

We look forward to sharing data from some of these ongoing trials at the upcoming ASCO meeting in early June with a number of presentations on lurbinectedin and zanidatamab. The second planned interim analysis for overall survival of the zanidatamab and chemotherapy arm of the HERIZON-GEA trial is still expected midyear.

At the time of top line readout, this arm showed a clinically meaningful effect on overall survival with a strong trend towards statistical significance compared to the control arm. The next pivotal Phase III trial for zanidatamab is in metastatic breast cancer patients who have progressed on or are intolerant to in HER2, and trial enrollment is progressing well.

We continue to expect to complete enrollment in the EmpowHER trial in the first half of 2027, with top line data anticipated in late 2027 or early 2028. Other earlier-stage trials continue to progress across new indications, including a potentially registrational pan-tumor basket trial and a neoadjuvant adjuvant breast cancer trial.

Looking ahead to later this year or early 2027, we anticipate the ongoing Phase III ACTION trial will have an interim overall survival readout. This trial is designed to confirm the benefit of Modeyso and support regulatory approval as frontline therapy directly following radiation instead of waiting for signs of tumor progression before treating with Modeyso.

We are working with dedicated focus to both realize the full potential of our near-term opportunities and to rapidly progress our pipeline. Our in-house research and development efforts are underway, and we look forward to sharing updates on those and further pipeline progress in the future.

Now I will turn the call over to Phil for a financial update. Phil?

Thanks, Rob. I'll start with high-level comments on our non-GAAP adjusted P&L, as shown on Slide 17.

Please note that our full financial results are available in today's press release and 10-Q. The outstanding execution of our field-based teams was reflected in record first quarter revenue of $1.07 billion, driven by 45% growth in our oncology portfolio, 18% growth in Xywav, and 15% growth in Epidiolex.

Strong underlying performance drove the vast majority of our revenue growth. I do want to point out 2 smaller items that also contributed to growth this quarter.

First, we had the normal 13 shipping weeks for our U.S. oncology product this quarter, while in last year's quarter, we had 12 shipping weeks.

This contributed about 2 percentage points to our worldwide revenue growth rate. Second, the significant devaluation of the U.S.

dollar led foreign exchange to contribute about 1.5 percentage points to our worldwide revenue growth. Moving down to P&L.

Our non-GAAP adjusted gross margin declined slightly year-on-year, primarily due to higher sales of products carrying royalties, namely Zepzelca and Modeyso. Non-GAAP adjusted SG&A expense decreased by about $164 million.

You may recall that in last year's quarter, we recognized litigation settlement expenses of $172 million. Excluding these expenses, SG&A increased by $8 million, driven by the inclusion of Modeyso expenses.

Non-GAAP adjusted R&D expenses increased by $13 million, primarily due to the inclusion of Modeyso clinical trial expenses and higher compensation-related expenses. Our non-GAAP adjusted effective tax rate this quarter was slightly lower than our full year 2026 guidance due to excess tax benefits from share-based compensation, while our shares outstanding for the quarter reflect the accounting effect of our higher share price on our convertible notes and employee stock plans.

At the bottom line, we posted very robust non-GAAP adjusted EPS of $6.34. Supported by our strong start to the year, we are reaffirming our full year 2026 revenue and expense guidance, including total revenue guidance of $4.25 billion to $4.5 billion.

Total revenue guidance for 2026 includes the assumptions you see on Slide 18. As a reminder, we assume competitive dynamics in our sleep business will increase in the second half of the year, including high-sodium generics gaining volume and one or more daytime weight-promoting agents potentially entering the narcolepsy market.

We also expect to see a decline in Xyrem and high sodium authorized generic revenues as generic high sodium oxybates build their volumes over the course of 2026. And as Sam mentioned earlier, we expect a decline in second-line use of Zepzelca.

Our Q1 performance and focus on disciplined capital allocation position us well to achieve our 2026 guidance. Moving to Slide 19.

Our balance sheet remains strong. We continue to generate significant cash from our business, recording $408 million of cash from operations in the first quarter of the year, and we ended the first quarter with $2.9 billion in cash and investments.

Our overall financial position and robust operating cash flow provides significant flexibility to invest in value-driving commercial and R&D programs as well as in promising corporate development opportunities to support our rare disease strategy. I will now turn the call back to Renee for closing remarks.

Thank you, Phil. I'll conclude our prepared remarks on Slide 21.

The first quarter of 2026 builds on the successes we achieved in 2025. Our focused commercial execution led to more than 19% growth in the first quarter.

And based on these results, we are on track to achieve our 2026 financial guidance. We look forward to several upcoming catalysts, including the second interim analysis of overall survival from the HERIZON-GEA trial midyear.

Top line readout for overall survival for the confirmatory ACTION trial for Modeyso is expected at the end of this year or early next year. And the top line readout from the trial evaluating zanidatamab in late-stage breast cancer post in HER2 treatment is expected in late '27 or early 2028.

We continue to build upon our proven scientific expertise and capabilities to make a meaningful impact for patients. Supported by our strong financial position, you should expect to see us invest in our commercial brands and pipeline and business development to broaden our portfolio in key strategic focus areas of sleep, epilepsy, and oncology in addition to other areas of rare disease.

I'd like to thank all our Jazz colleagues for their efforts and dedication to making a difference in the patients' lives that led to an exceptional first quarter. We are relentlessly focused on continuing to execute and deliver life-changing medicines to patients.

That concludes our prepared remarks. I'd now like to turn the call over to the operator to open the line for Q&A.

Question on zanidatamab for breast cancer. So if we assume zani beats Herceptin in breast cancer and gets approved one day for use in the post in HER2 setting, how do you expect physicians to make decisions about how to sequence agents in the context of a lack of data for other products post in HER2, among other things?

I'm happy to address that, Jess. This is Rob Iannone.

We became very interested in this space based on good advice from many key experts in the field. And the fundamental issue is that once HER2 moves to frontline, there's very little data about which HER2 agent to select as subsequent therapy.

So the trial that we're running 303 will be the first time that we definitively in a randomized setting, evaluate zanidatamab versus what would be considered a standard of care. So we expect to be out ahead with important data that will inform decisions about whether to use zanidatamab or other HER2 agents in that space.

Congrats on the quarter. Maybe one on Modeyso.

Do you have any updated thoughts on sort of the size of this patient population? I think historically, it was thought that it was maybe 2,000 or 3,000, but it sounds like it sounds like already hitting 500 patients.

So any thoughts on that total opportunity just given the strength of that launch? And maybe a follow-up, if I can, on M&A.

Kind of what's your latest thinking in terms of where you'd like to go? Obviously, we've seen a lot of activity in the past few weeks in different areas.

Kind of what's the sweet spot in terms of size and area of focus for Jazz going forward?

Yes. Hello, Sam here.

I'm happy to take the question on Modeyso to start with. Yes, we're extremely pleased with the launch so far, $41 million in Q1 really gives us a lot of confidence around achieving that $500 million peak opportunity in the U.S.

And as you mentioned, we've had 500 patients treated since launch. And I think that just reflects the very high unmet need that we see in this space.

Overall survival from diagnosis is just 1 year. So this product has had a meaningful impact, and it's supported by high awareness from physicians and, obviously, very strong patient advocacy support as well.

In terms of the size of the patient population, I think our best estimates are aligned to what you mentioned there. And over time, of course, we'll continue to evaluate that.

But we do see potential upsides in duration of treatment as well as the size of the population. What we've seen so far is that patients are staying on treatment for longer than we initially anticipated.

We'll have to wait for this cohort of patients to really mature before we get a really good handle on whether the duration of treatment exceeds that, that we saw in the trial, which is around about 10 months. But extremely happy with the start.

I think our teams have done an excellent job really executing this launch well in such an important area of medical need.

And Joe, this is Renee. I'll jump in on BD.

So we are highly engaged on the BD front, and I do expect us to have deals announced over the course of this year. We do have a clear strategy that is focused on expanding our presence in rare disease, in particular, where we believe there's a significant unmet need.

So strengthening our current areas of epilepsy, sleep, and rare oncology, also expanding into new areas of rare disease, areas where we think we can leverage our capabilities and our footprint to continue to scale our business while driving further growth and profitability. In terms of the deal types, we -- it really depends on the asset and the transaction at hand, but we are looking at licensing structured deals, also outright M&A.

I think the key here to being successful in BD is identifying value or risk that others don't see and then staying myopically focused on execution as we did with the Chimerix launch, the Chimerix acquisition and subsequent Modeyso launch. And we have very strong momentum now with the new CBO, Chief Business Officer, on board as of January 1.

Importantly, we are well positioned to execute. Phil mentioned, we have a strong financial position, $2.9 billion in cash and cash equivalents on the balance sheet, strong cash flow.

And while M&A has picked up, we do believe there is still a lot of substrate that is actionable and well aligned with our strategic priorities.

I wanted to stay with, you mentioned epilepsy. I just wanted to touch on that.

You've been making a lot of investments in that area, both with Epidiolex, [ Cenobamate ] asset, you also have JZP-047, and now you mentioned potentially looking at BD there as well. So I guess I'm just curious how you're thinking about that area, to what extent it's a continued focus and how you think about either synergies or risk of cannibalization across sort of many different assets there?

Yes. Thanks for the question.

This is Renee. I would say this is definitely an area of focus for us.

There continues to be significant unmet need across the epilepsy space. You see a strong amount of polypharmacy here with respect to multiple -- sorry, multiple medications generally on board, in particular, when we're looking at serious refractory epilepsies.

We think with the position that we have with Epidiolex being the #1 branded product and having the very long durability out to the very late 2030s, it gives us greater opportunity to continue to build around that franchise to build scale. I'm thrilled to see additional opportunities for patients with the strong data that we've been seeing come out with a number of companies in whether that's on the proof-of-concept side, starting to go into registrational studies or work that's happening early in pipelines.

As we think about ourselves, we think there is plenty of room and need -- unmet need for patients to continue to see new mechanisms explored and new options for patients. So we do think there's still plenty of substrate, a great opportunity for us as a leader in epilepsy.

You will note, last quarter, we said we were advancing the first molecule coming out of our labs that was not just a formulation play, but an innovative target novel mechanism coming out of our lab that went into patients in the epilepsy space. So we will continue to invest here, and we're excited about the opportunities.

Just want to circle up on Modeyso again. Obviously, it's been exceedingly promising since the outset, and you have a potential to move into first-line treatment.

I guess my question is, how should we think about the potential move into first-line treatment? Does this significantly expand the market?

Should we think about this like we think about Zepzelca moving into first line and how it significantly inflected growth? I guess I'm trying to understand the magnitude given that most patients are in first line, progress to second line.

Is it only about duration? Or is there a population opportunity there?

Yes. Hello, Annabel, happy to take that.

Yes, I think there's 2 factors when we consider the ACTION study and what that will do for Modeyso and for improving the treatment to patients. Some patients don't make it to second line.

So of course, there are more patients available to be treated. But having the opportunity to get Modeyso to patients before they progress will mean that the duration of treatment should be longer if they can use it straight after radiation.

So those 2 things, I think, do -- will contribute to us achieving the $500 million peak potential, which does incorporate an assumption that we will have that first-line label. Rob, anything more to add on that?

I mean you covered it well. I'd just point out that sometimes it's hard to judge progression in these patients.

And then as you point out, once it's clinically apparent in addition to imaging, patients may rapidly progress and not benefit from second-line therapy. So the opportunity to start Modeyso right after the radiation therapy really does potentially add a significant benefit to patients and, ultimately, duration of therapy.

Sam, can you talk about Epidiolex OUS? I heard Phil talk about the FX impact, but those numbers couldn't have just been FX, something is doing pretty well there.

So maybe just talk, was there any particular country? Was there any buy-in?

Anything unusual there? And maybe you could just comment on Rylaze as well, which happened to have a really good quarter and what was happening there?

Yes. Thanks for the question, Marc.

Yes, it's great to see the performance outside of the U.S. for Epidiolex, very strong growth indeed.

Around about 2/3 of that, I believe, was volume, and there was about 1/3 due to FX and some gross to net benefits from places like the U.K. with a VPAG adjustment that happened there.

And I think really, this is just down to terrific execution by our teams. As you know, Epidiolex was launched a little bit later in Europe.

So there's still quite some opportunity to continue to penetrate in the pediatric segment, but of course, also in the adult segment, which is a focus for both the U.S. and the ex-U.S.

business. And then your other question around Rylaze.

Yes, Rylaze, yes. Rylaze delivered a strong quarter, $104 million, which was 10% revenue growth.

But that was comparing to quite a low Q1 '25. So I think the performance that we've seen in this quarter is in line with the prior quarters that we've seen other than the Q1, which is a low point.

What we've seen with Rylaze is the COGS impact that started in '24 has been fully realized now. And our focus continues to be on making sure that patients -- appropriate patients can receive Rylaze that they're switched at the first sign of a hypersensitivity reaction and the opportunity to continue growth in AYA.

But I think that $100 million per quarter for Rylaze is a good kind of stable base for us currently.

This is Jordan Becker on for Etzer Darout. Congrats on the impressive quarter.

Maybe just one, if we could expand on any second half dynamics for oxybates now with a full quarter in the rearview. Maybe if you could provide some more color on any potential competitive pressure from LUMRYZ specifically?

And then on that, maybe any perceived pressure to IH growth down the line if LUMRYZ is approved in IH?

Yes, I'm happy to take that question on Xywav. Yes, we're very pleased with the continued momentum for Xywav, $408 million this quarter, 18% revenue growth, and a really healthy 12% volume growth.

We continue to see really good patient adds, 425 net patient adds in the quarter, most of them continuing to come from IH, 300 net patient adds for IH, which is consistent with what we've seen in prior quarters. So we finished the quarter with 16,600 active patients.

And when we look ahead to the outlook for Xywav for the remainder of the year, obviously, we're very pleased with the momentum that we're taking into the second quarter. We still have continued strong payer coverage, more than 90% commercial lives covered.

Nothing has changed around the nature of our Xywav business in the first quarter of this year. And our 2026 full year guidance does include assumptions that generics will build volumes in the second half of the year as well as the potential for the entry of new wake-promoting agents entering the market in the second half of the year in the NT1 narcolepsy segment.

But we believe Xywav will continue to have a really important place in therapy. We've invested in some really meaningful evidence generation, XYLO and the DUET studies, which show the importance of having a low-sodium option.

And as you mentioned, it's the only option approved for IH and the DUET study, which shows just how effective Xywav is as a nighttime agent. And we believe those 2 benefits will continue to resonate strongly with physicians and patients, of course.

This is [ Charlie ] on for Brian. I was just wondering if you could give us a sense of the size of the opportunity for Epidiolex in the adult and long-term care setting.

And maybe some more color on the initiatives you're taking there with the new formulation? As well as would be curious to hear, will you be sharing any data from the Phase Ib in focal onset when you get that?

And do you have any idea in terms of timing there as well as what your expectations are for the setting for Epidiolex?

I'm happy to take the first part of your question in relation to the adult segment, and then I'll hand over to Rob to talk about the study. Yes, we're very happy with the performance of Epidiolex in the first quarter of this year, $250 million, 15% revenue growth and 16% volume growth.

As you probably recall, Epidiolex was launched initially very much as a pediatric drug, and we've seen really good penetration in that segment, a leading agent, obviously, for pediatric patients. One area that we do continue to see opportunities in is in that adult segment, particularly in long-term care facilities.

So we've made some specific investments there with a dedicated team focusing on those facilities. And we've also invested in a diagnostic tool, REST-LGS tool because we know that adult patients with LGS often go undiagnosed.

So we've supported physicians to help ensure that those patients can get a definitive diagnosis and benefit from Epidiolex. In addition to that, one of the hallmarks of Epidiolex is the very long persistency that we see, but we do see an opportunity to drive that even further.

We know that patients that are enrolled onto our JazzCares program, which also gets the support of a Nurse Navigator, they do stay on treatment longer. So we've got a particularly focused effort now on ensuring that as many patients as possible can benefit from our JazzCares suite of services, and we believe that will drive even longer durations of treatment for Epidiolex.

In addition to that, we're making quite significant investments in evidence generation. We have the EpiCom study in TSC and the BECOME survey, which has been focused on adults, which really just underlines the benefit that Epidiolex has not just for the control of seizures, but also for controlling some of the non-seizure symptoms that these patients experience as well.

And that's one of the very significant differentiating benefits of Epidiolex. So overall, we're very encouraged by the momentum that we have with Epidiolex, but also really see a lot of long-term potential to continue to grow Epidiolex into the future, particularly in that adult segment.

Thanks for the question on the focal onset seizure study. We're super excited about it.

There's a lot of interest from epileptologists to more formally evaluate Epidiolex in this setting. As you know, doctors and treaters think about epilepsy in terms of types of seizures.

And we have lots of data showing activity of Epidiolex across really every type of seizure with some preliminary evidence in focal onset seizures as well. This is an evidence generation study to go deeper into this particular population, and we would intend to publish this as soon as we have data available to do so.

We haven't given any specifics on that yet. After a little more time lapses and we get a good sense of the enrollment rate, we may be able to update further.

I had a long-term competitive landscape question on your oxybate business. So your competitor has Valiloxybate, the sodium once-nightly or potential no sodium once-nightly product that's in development.

To the extent that reaches the market, can you talk about how that could impact your Xywav business, both in terms of narcolepsy and the IH setting? And just in general, how are you planning to respond competitively to overall a more crowded landscape?

The obvious is, of course, of orexin, but also next-generation oxybate products as well?

Maybe I can step in on that, and then I'll ask Rob to comment on how we're viewing orexin. So I would first point to the fact that Xywav has been competing for the last 2 years with a number of high-sodium options on the market.

And over that time, we have not only built a strong group of patients that are relatively persistent in terms of their use of oxybate, the specific relief and flexibility that they receive from Xywav and also being the only option available for IH. We've done a lot of work in the market in terms of disease awareness.

One of the areas that we've invested quite a lot in that Sam has spoken to earlier is the patient support services. I think that is highly differentiating for Jazz in terms of the extent of our services and the way that we have deployed those.

And so we will continue to ensure that the unique differentiating benefits of Xywav as well as our various support services are well understood in the market. I would also note that we do, from a patent perspective, have a lot of confidence in our overall patent estate.

So when you're thinking about the various programs that are out there that may be looking for a 505(b)(2) sort of path. From that perspective, we do have robust patents that include many Orange Book listed patents out to 2033 and '37 and then an Orange Book listed IH patent out to 2041.

But maybe I'll also invite Rob to comment with respect to orexins coming into the market and our view there.

Yes. We've been following orexins carefully and our conclusion is that it's likely to be complementary to Xywav.

As Sam mentioned, alluding to the DUET study, we have significant data showing that the root cause in hypersomnia, such as narcolepsy type 1 and 2 as well as IH is really disrupted nighttime sleep. And oxybates are the only therapy that can address the disrupted nighttime sleep directly.

And Xywav, of course, the only low sodium formulation that we believe is safest for patients who are at a high risk for cardiovascular outcomes. Certainly, orexins are showing to be potent daytime alerting agents.

There's some preliminary data showing though that you can have insomnia, especially with the longer half-life formulations. And the limited PSC data that are out there suggests that certainly not improving disruptive nighttime sleep and may actually on the first half of the night, be impacting it negatively with the reports of insomnia.

So we continue to think that this important space to follow. We have an orexin in development still.

And -- but we think ultimately, this is going to be complementary to Xywav.

Congrats on all the progress. Just want to ask about Zepzelca IP here.

I see a few new Orange Book listed patents here in 2025. So they go all the way to 2040.

So how should we think about the life of Zepzelca beyond 2029, that's the comp of matter patent at this point?

Yes. Thanks, Mohit.

This is Renee. So we do have a strong patent estate for Zepzelca.

And as you noted, we do have multiple patents that extend out to 2040. We're also pursuing multiple new patents with the patent office that would also extend out to that time frame with additional applications, whether that be combo therapies, formulations, or methods of treatment.

We have also stepping back and speaking to the ANDA filers that we've disclosed, we have filed suit against all 5 ANDA filers. And as a result of filing that suit, a stay of approval is in effect for up to the 30 months as is imposed by the FDA.

And so while we're not going to speak broadly to active litigation, we do feel that we have a strong patent estate. And as we have more clarity and information on that, we will be certain to share that.

Just one, Phil, on Xywav, I apologies if I missed this, but at the beginning of the year, I think you guided to flat to mid-single-digit growth for Xywav, given the growth of nearly 20% in 1Q. Just wondering if we should be assuming that we're coming in towards closer to the high end of that number?

Or were there some onetime dynamics in the 1Q number to call out? And how should we think about zanidatamab pricing OUS and any MFN-related considerations?

Sure. Thanks for the question, Jason.

On Xywav, in the U.S., really pleased, as Sam mentioned, with the great execution of our field-based team. In terms of sort of underlying growth, we had volume growth of about 12% here in the first quarter.

There was a bit of additional pickup coming from net price, primarily gross to net favorability with both mix of business and then patients successfully transitioning more quickly than in the past back on to their insurance in that first quarter reauthorization period. So that is something that is more of a first quarter phenomenon.

We wouldn't expect to see that kind of net price pickup quarter-on-quarter as we get into Qs 2 through 4, but definitely pleased with Xywav performance in the first quarter sets us up nicely. We're achieving the full year guidance.

I think that also applies to this total revenue guidance as well, not just Xywav. And then for the MFN zani, right now, the MFN considerations, as you know, are a bit uncertain.

You've got some sort of conflicting input out there, certainly GLOBE and GUARD are as proposed to use a basket of ex-U.S. countries to provide reference pricing for the U.S.

So we'll certainly be taking that into account as we look at the strategy for getting Ziihera to patients outside of the U.S., which is certainly a priority of ours, but one that we will need to take account of the current situation here in the U.S. as we move forward.

I'm not sure, Sam, if you'd like to add any your thoughts from a commercial perspective or Renee more from a corporate strategic perspective.

I think you've covered it nicely, Phil.

I had a follow-up on the comments related to the oxybate franchise, particularly Xywav. I think at the beginning of the year, you talked about anticipating the potential for some additional headwinds either on pricing side or just in terms of access with the entry of generics.

Maybe if you could sort of talk about some of the dynamics around whether you're seeing any pushback on the use of Xywav, particularly in narcolepsy? And how do you see the utilization in narcolepsy evolve with more generics kind of on the market?

And then just on the Modeyso ACTION trial, can you sort of talk about what -- which interim OS analysis will be done by the time you have the data readout in late 2026, early 2027, and just sort of your confidence around the time line of that readout?

I'm happy to take the question relating to Xywav. Yes, of course, we've seen 2 multisource generics enter the market in Q1.

As yet, we haven't seen any impact on Xywav business so far. As I mentioned previously, we continue to have a strong payer coverage supporting the use of Xywav.

So nothing really has changed in the nature of our business for Xywav. But of course, it is still early days for the generics in the market.

We do anticipate that as their volume grows through the course of the year, then we may start to see some actions taken by payers. That may include utilization management.

We don't know yet. But we're very confident that Xywav offers a really important and differentiating option for patients, being the only low-sodium option, the only product approved for IH.

And of course, it has already demonstrated how effective it is as a nighttime agent and the impact that has on daytime symptoms. So we've obviously carried strong momentum throughout the last 12 months and into this year, and we're in a strong position as we go into Q2.

Maybe I'll hand over to Rob for the question on Modeyso.

I'll go ahead, Sam, just add one thing real quickly as we think about what we're seeing with Xywav before we go on to Rob for Modeyso. Certainly, the dynamics are a bit unusual in the first quarter given reauthorization.

But I do think we're seeing continued support by patients and physicians of the unique benefit that Xywav offers from looking at the net patient adds. I think LUMRYZ net patient adds were announced roughly 100 adds this quarter, like the 100 last quarter.

Our numbers just in narcolepsy have been larger than that in each of those 2 quarters. Again, I think underscoring this unique benefit that only Xywav can offer and the safety advantage it confers being valued by patients as well as physicians.

So we're in a great position from that perspective as well as we think about the back part of the year and how things could play out. Rob?

Yes. So Ami, the ACTION trial is an OS-based endpoint, and there's one interim analysis and then a final analysis.

The projections we gave are based on our current understanding of the events because it is an event-driven trial. And certainly, if the events slow over time, that could change, but we'll update as appropriate as time goes on.

I first wanted to ask on the timing of a potential NCCN guideline incorporation for zani in GEA. Do you have any sense of relatively when that might occur versus the PDUFA date and how important is a Category 1 recommendation to drive uptake?

And then in breast cancer, for zani, I wanted to get a sense of how you're thinking about the opportunity size in the different settings. So obviously, you're looking at post HER2, but I think you're also looking at neoadjuvant and adjuvant.

And so I was just curious as to your thoughts on size of the opportunity in those various things.

Great. On the NCCN guidelines, we proactively submitted the abstract data because it was available.

We will certainly update NCCN with the full manuscript as soon as that's available, and we hope that gives them everything they need to make a prompt decision on that and adoption, which we expect. Certainly, we think the data speak for itself.

I mean head-to-head against Herceptin, zanidatamab definitively wins. Clear that tislelizumab is adding and there's likely to be a synergy between zani and tislelizumab as demonstrated by the activity in the PD-L1 negative subset, supporting its use upfront with tislelizumab.

And so we think those data speak for themselves, and that should be reflected in NCCN.

Sorry, just to finish off the remainder of that question there. Yes, I mean, NCCN guidelines inclusion, obviously important.

We think that the data supports a Category 1 inclusion. If it comes before the launch, then that will open up access ahead of regulatory approval.

Of course, we don't promote that ahead of regulatory approval, but certainly, that will make it easier for physicians to provide access to their patients. And yes, the breast cancer opportunity, obviously, very significant, significantly larger than either the BTC opportunity or the GEA opportunity with many more patients that can potentially benefit from zanidatamab.

So we're excited, obviously, about that for the long-term potential for HER.

Thanks, operator. I'd like to close today's call by thanking all our partners and stakeholders for their continued confidence and support.

We look forward to sharing further updates on the potential approval of zanidatamab in GEA and additional meaningful progress with you over the remainder of the year. So thank you for joining us, and have a great day.