Jazz Pharmaceuticals - Earnings Call - Q1 2025

Executive Summary

• Q1 2025 total revenues were $897.8M, down 0.5% YoY and below consensus ($984.0M), while non-GAAP EPS of $1.68 missed consensus ($4.66) due to a $172M Xyrem antitrust settlement charge booked in SG&A; GAAP LPS was $(1.52). Revenue Consensus Mean: $983.8M*, Primary EPS Consensus Mean: $4.66*; Primary EPS - # of Estimates: 16*, Revenue - # of Estimates: 17*. Values retrieved from S&P Global.
• Neuroscience strength continued: Xywav +9% YoY to $344.8M and Epidiolex +10% YoY to $217.7M; oncology was softer (Rylaze −8% YoY, Zepzelca −16%) given protocol changes and competition.
• 2025 guidance: Total revenue affirmed at $4.15–$4.40B; SG&A (non-GAAP) raised to $1.47–$1.53B and R&D (non-GAAP) raised to $760–$810M to reflect Chimerix acquisition; non-GAAP ANI lowered to $250–$350M (from $1.4–$1.5B prior) given $885M acquired IPR&D related to Chimerix and the litigation settlements.
• Catalysts: ASCO oral presentation for Zepzelca 1L ES-SCLC maintenance data (June), HERIZON‑GEA‑01 top-line in 2H25, and dordaviprone PDUFA on Aug 18, 2025; management reiterated confidence in 2025 revenue outlook and minimal direct tariff impact in 2025.

What Went Well and What Went Wrong

What Went Well

• Xywav and Epidiolex delivered growth: Xywav +9% YoY to $344.8M and Epidiolex +10% YoY to $217.7M; management cited robust demand and patient adds, with ~14,600 active Xywav patients exiting Q1 (≈450 net adds).
• Pipeline/regulatory progress: sNDA submitted for Zepzelca 1L ES‑SCLC maintenance; CHMP positive opinion for zanidatamab in 2L BTC; HERIZON‑GEA‑01 PFS readout expected 2H25.
• Chimerix acquisition completed, adding near-term commercial opportunity (dordaviprone) with Priority Review and Aug 18, 2025 PDUFA date.

What Went Wrong

• Oncology softness: Rylaze −8% YoY to $94.2M (COG protocol timing) and Zepzelca −16% YoY to $63.0M (competition, delayed progression to 2L), driving overall oncology net sales down 11% YoY.
• Litigation impact: $172.0M SG&A charge tied to Xyrem antitrust settlements reduced non-GAAP EPS by $2.34 and GAAP by $2.38; GAAP net loss was $(92.5)M.
• Top-line miss vs Street: Revenue ($897.8M) and non-GAAP EPS ($1.68) missed consensus, partly reflecting seasonality (Epidiolex inventory burn) and one fewer U.S. oncology shipping week in the quarter.

Transcript

Operator (participant)

Hello, and thank you for standing by. My name is Tiffany, and I will be your conference operator today. At this time, I would like to welcome everyone to the Jazz Pharmaceuticals first quarter 2025 webcast conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star, followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one again. We kindly ask that you limit yourself to one question for today's call. Thank you. I would now like to turn the call over to Executive Director of Investor Relations, Jeff McDonald. Please go ahead.

Jeff Macdonald (Executive Director of Investor Relations)

Thank you, Operator, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its 1st quarter 2025 financial results. The slide presentation accompanying this webcast is available on the Investor section of our website. Investors should also refer to the press release we issued earlier today that is available on our website. On the call today are Bruce Cozadd, Chairman and Chief Executive Officer; Renee Gala, President and Chief Operating Officer; Rob Iannone, Executive Vice President, Global Head of R&D and Chief Medical Officer; and Phil Johnson, Chief Financial Officer. On slide two, 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 and goals, 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 the statements contained in today's press release, in our slide deck, and the risks and uncertainties described under the captioned risk factors in our annual report on Form 10-K for the fiscal year ended December 31st, 2024, and our subsequent filings with the SEC, including our quarterly report on Form 10-Q for the financial quarter ended March 31, 2025, which identifies certain factors that may cause the company's actual events, performance, and results to differ materially from those contained in the forward-looking statements made on today's webcast. We undertake no duty or obligation to update our forward-looking statements. As noted on slide three, 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 Investor section of our website.

I'll now turn the call over to Bruce.

Bruce Cozadd (CEO)

Thanks, Jeff. Good afternoon, everyone. Thank you for joining us today to discuss Jazz's first quarter 2025 results. I'll start on slide five. Jazz started the year with strong momentum following a productive 2024, and we're pleased with the meaningful progress we've made across the business in the first quarter of 2025. Our focus on execution and operational excellence resulted in solid commercial performance led by Epidiolex and Xywav, and significant progress across our R&D pipeline. We submitted a supplemental new drug application, or sNDA, to expand Zepzelca into first-line maintenance in extensive stage small cell lung cancer and received a positive CHMP opinion recommending the marketing authorization for zanidatamab in advanced HER2-positive biliary tract cancer, or BTC, in the European Union. In addition, the acquisition of Chimerix has further strengthened our presence in rare oncology. On the commercial front, we generated $898 million in total revenues across our portfolio.

Our neuroscience portfolio had a strong start to the year, with Xywav growing 9% year-over-year, remaining the number one branded treatment for narcolepsy as measured by revenue, and the only therapy approved to treat idiopathic hypersomnia, or IH. We saw strong Epidiolex demand as revenues increased 10% year-over-year, and we remain confident in its blockbuster potential. While we experience near-term headwinds with certain oncology products, our oncology portfolio is poised for growth with three potential regulatory approvals in the coming months, including dordaviprone, Zepzelca expansion into first-line maintenance therapy in the U.S., and zanidatamab advanced BTC in Europe. Moving to R&D, we're advancing promising opportunities in our pipeline. The HERIZON GEA-01 phase III trial evaluating zanidatamab in first-line gastroesophageal adenocarcinoma, or GEA, remains on track to read out in the second half of this year.

We continue to progress other key zanidatamab clinical trials, including the phase III Empower BC-303 trial in breast cancer. We are looking forward to sharing important data on Zepzelca, zanidatamab, and dordaviprone at ASCO in June. We added dordaviprone to our pipeline through the Chimerix acquisition, which closed in April, enhancing our presence in rare oncology and bringing a near-term commercial opportunity to help patients with limited treatment options. Given its patent protection into 2037, with possible extensions and the potential for expanded use in the front-line setting, we view dordaviprone as a meaningful and durable revenue opportunity for Jazz. We are well-positioned with respect to the impact of potential tariffs and have maintained financial flexibility supported by our strong balance sheet and cash flow. We remain confident in our top-line revenue guidance and have updated our financial guidance to include the recent Chimerix acquisition and litigation settlement charges.

I'll now turn the call over to Renee to discuss our commercial performance, after which Rob will cover our R&D pipeline. Phil will then provide a financial overview and discuss our updated guidance, and after that, we will open the call to Q&A. Renee?

Renee Gala (President and COO)

Thanks, Bruce. I'll begin on slide seven to discuss the continued progress of our commercial portfolio, starting with our sleep therapeutic area. I'm pleased to report total revenue for sleep, which includes Xywav and Xyrem net product sales plus royalties from high-sodium oxybate-authorized generics, or AGs, was approximately $431 million in the 1st quarter of 2025. Xywav net product sales were approximately $345 million in the 1st quarter, an increase of 9% year-over-year. As a reminder, we typically see seasonality in our sleep revenue due to reauthorizations at the beginning of each year. Despite the expected seasonality, Xywav had a robust quarter of patient adds driven by strong execution from the field teams, and we continue to be excited about the direction of our sleep portfolio.

There were approximately 14,600 active Xywave patients exiting the 1st quarter, representing an increase of approximately 450 net patient adds compared to the fourth quarter of 2024, comprised of 125 narcolepsy patients and 325 IH patients. Narcolepsy patient adds consisted predominantly of oxybate naive patients, along with patients transitioning from high-sodium oxybates. Our efforts to educate on the importance of reducing sodium intake and the increased risk of cardiovascular comorbidities among narcolepsy patients continue to resonate with HCPs and with patients. We see the most opportunity for patient growth from the IH market, where Xywave is the 1st and only FDA-approved therapy. As we continue to build this market, disease education on the benefits of using a nighttime therapy to address sleep inertia and symptoms like brain fog and excessive daytime sleepiness for IH remains important to drive prescribing.

We've launched consumer-targeted digital and media campaigns to increase disease awareness, coupled with promotion and medical education to HCPs. These campaigns are performing well, contributing to the growth of the IH market, and we continue to enhance our field effectiveness to optimize our impact for patients. Turning to slide eight in Epidiolex, Epidiolex had net product sales of approximately $218 million in the 1st quarter, a 10% increase year-over-year. Growth was primarily driven by underlying demand and, to a lesser extent, favorable U.S. payer mix, partially offset by U.S. inventory burn. Exiting the 1st quarter, inventory was lower than we would typically see at this time of the year.

Our Epidiolex commercial and medical teams have been executing well, with key drivers of demand growth in the U.S., including continued data generation on the benefits of Epidiolex beyond seizure control, expanded reach to adult patients and long-term care facilities, along with broad quality access and the Nurse Navigator program. We're pleased with the growth of Epidiolex and expect it to reach blockbuster status in 2025. Moving to oncology on slide nine, Rylaze net product sales were approximately $94 million in the 1st quarter of 2025, a decrease of 8% year-over-year. As we previously noted, Rylaze sales have been impacted by the update to Children's Oncology Group, or COG, pediatric treatment protocols for acute lymphoblastic leukemia made in mid-2024.

Based on feedback from KOLs about their expected use of asparaginase, we continue to see the impact to Rylaze as temporary, with revenue normalizing during the second quarter of 2025. We are making steady progress in the adolescent and young adult market and continue to place Zepzelca back on a growth trajectory. Moving to slide 11 in our ongoing zanidatamab launch. In December of last year, FDA approved zanidatamab, the first and only dual HER2-targeted bispecific antibody approved for HER2-positive second-line BTC in the U.S. We recognized approximately $2 million in net product sales in the first quarter of 2025. While our early launch reception from HCPs has been positive, we are hearing initial customer experiences are aligned with the clinical profile we observed in clinical trials.

As a reminder, BTC is a rare disease with a limited number of patients, and we expect revenue contribution to be modest from this rare cancer. We expect this initial launch in second-line HER2-positive BTC will help us bring significant benefit for patients. In addition, the BTC approval helps healthcare professionals gain meaningful experience with zanidatamab prior to its potential indication in GEA. I will now turn it over to Rob for an update on our pipeline and upcoming milestones. Rob?

Rob Iannone (Executive VP and Chief Medical Officer)

Thanks, Renee. I'll begin on slide 13. I'm excited about our pipeline and the significant progress we have made on key programs, with additional milestones expected this year. Looking first at oncology, we completed the submission of an sNDA to FDA to expand the Zepzelca label to include maintenance therapy in first-line extensive stage small cell lung cancer for patients who have not progressed during induction chemotherapy. The submission is based on statistically significant and clinically meaningful progression-free survival, or PFS, and overall survival, or OS, data from the phase III and IV day trial of Zepzelca in combination with atezolizumab compared to atezolizumab alone. The results have the potential to be practice-changing, and we look forward to showcasing the data in an oral presentation at ASCO on Monday, June 2.

Presentation in a peer-reviewed form also enables us to submit the data for potential inclusion in NCCN guidelines and compendia listing. We also remain on track for top-line readout of PFS data from the HERIZON GEA-01 trial in the second half of this year. The first interim analysis of OS will also occur at this time. We are encouraged by the positive results from two independent phase II trials of zanidatamab in first-line GEA that demonstrated increased median PFS, duration of response, and confirmed objective response rates. If the phase III trial findings are positive, we expect the data will support registration based on potentially clinically meaningful PFS and supportive OS data. Three zanidatamab presentations have been accepted at ASCO, including updated overall survival data from the phase II first-line GEA trial. In addition, there will be an oral presentation on the safety and efficacy of dordaviprone.

Turning to neuroscience, we recently initiated our planned phase IB trial to evaluate the efficacy, safety, tolerability, and pharmacokinetics of JZP-441 in participants with type 1 narcolepsy. With respect to our Epidiolex trial in Japan, we are continuing to collect long-term safety data, which was included in the trial design for 26 and 52-week analyses. We observed numeric improvements in both the primary and several secondary endpoints, and we remain on track to meet with the Japanese health authorities in mid-2025. As outlined on slide 14, zanidatamab has proven to be a unique, differentiated, and highly effective dual-targeted HER2 therapy. zanidatamab provides opportunities across multiple HER2-positive solid tumors and represents a global opportunity for Jazz in multiple markets.

Following the FDA approval of zanidatamab in second-line BTC last year, the CHMP recently adopted a positive opinion recommending the marketing authorization of zanidatamab for the treatment of adults with previously treated, unresectable, locally advanced, or metastatic HER2-positive BTC. We look forward to the European Commission's decision and for the opportunity to bring a new treatment option to patients in Europe if approved. We have also completed recruitment for our phase III trial evaluating zanidatamab in first-line GEA and expect top-line PFS data later this year. The overall development program for zanidatamab includes multiple registration-enabling trials, including pivotal trials in first-line BTC, first-line GEA, advanced breast cancer, and in a pan-tumor basket trial, focused on areas where we believe Zani has the potential to emerge as the preferred HER2-targeted therapy. This comprehensive development program underscores our confidence in zanidatamab's potential.

Turning to slide 15, we are also very excited that the Chimerix transaction has been completed and thrilled to welcome our new colleagues to Jazz. Our team is now engaged and working toward the shared goal of delivering dordaviprone to patients. dordaviprone is a groundbreaking, first-in-class small molecule in development for H3 K27M-mutant diffuse midline glioma, a rare high-grade brain tumor that most commonly affects children and young adults. There are currently no approved drug therapies for these patients, and the median overall survival from diagnosis is approximately only one year. Multiple clinical studies have demonstrated dordaviprone's benefit in patients with recurrent H3 K27M-mutant diffuse midline glioma, both as monotherapy and in combination with other treatment approaches, including radiation, with a consistently favorable safety profile.

The FDA has accepted an NDA for dordaviprone, seeking accelerated approval for treatment of H3 K27M-mutant diffuse midline glioma in adult and pediatric patients with progressive disease following prior therapy. The application has been granted priority review and assigned a PDUFA target action date of August 18 of this year. Based on communication with the FDA to date, we do not expect the agency to hold an oncology drug advisory committee meeting in connection with the review of the NDA. Beyond the recurrent disease setting, dordaviprone is being studied in the ongoing phase III ACTION trial, evaluating its use in newly diagnosed H3 K27M-mutant diffuse midline glioma patients following radiation treatment. This trial has the potential to confirm the clinical benefit of dordaviprone in recurrent H3 K27M-mutant diffuse midline glioma and potentially extend this treatment option into the front-line setting.

We believe that dordaviprone has the potential to transform the standard of care for this underserved patient population with very limited treatment options. Now I will turn the call over to Phil for a financial update. Phil?

Phil Johnson (CFO)

Thanks, Rob. I'll start with our top-line results on slide 17. As a reminder, our full financial results are available in our press release, which is available today, and in our 10Q, which will be filed tomorrow morning. In the 1st quarter of 2025, we recorded $898 million in total revenues. I'll note our 1st quarter revenues have historically been affected by several factors, including reauthorizations and inventory build in the latter part of the prior year, which typically burns off in the 1st half of the following year. As Renee mentioned, for Epidiolex, we saw more of this burn in the 1st quarter of this year. Despite these factors, Xywave and Epidiolex revenues grew 9% and 10% year-over-year, respectively. Our oncology product experienced a decline relative to the 1st quarter of 2024.

In part, this was driven by having one fewer shipping week in the 1st quarter of 2025 compared to the 1st quarter of 2024. In addition, the decline was primarily driven by our two largest oncology products, Zepzelca and Rylaze. As Renee noted earlier, we believe we have line of sight into our assumption of growth for these products in the coming quarters. As I'll highlight on the next slide, we are affirming our total revenue guidance for 2025 based on our conviction in the strength of our overall commercial portfolio. Adjusted net income and earnings per share in the 1st quarter of this year were impacted by a charge related to certain Xyrem antitrust litigation settlements. This $172 million charge to SG&A in the 1st quarter reduced our adjusted net income by $146 million and our GAAP and non-GAAP EPS by $2.38 per share and $2.34 per share, respectively.

Before discussing our updated 2025 financial guidance, I'd like to comment on tariffs. Now, I'm sure we'll have several questions on this topic during the Q&A session, so I'll limit my commentary to the most essential items. I'll start with the tariffs already enacted on China, Mexico, and Canada, as well as the general 10% tariff levied more broadly. For 2025, we anticipate no direct financial impact from these tariffs and currently expect that any indirect impact resulting in inflation on goods we purchase can be managed within our existing internal budgets and external guidance. We won't speculate on the potential impact of future tariffs on pharmaceutical products imported into the U.S. at some hypothetical rate. As you'd expect, we've evaluated various scenarios and are positioned to comment in a timely manner if and when such tariffs are enacted. I can say that we have sufficient inventory in the U.S.

to serve all or nearly all of our 2025 needs for each of our products. Consequently, we expect that any impact on our 2025 financials would be de minimis, if any, and unlikely to affect our guidance. With that context, let's move to our updated 2025 financial guidance. Now, at first glance, the updates may seem complex. In reality, there are three drivers for the updates, and I think you'll find they're pretty straightforward. Those three drivers are the Chimerix acquisition, certain Xyrem antitrust litigation settlements, and slightly revised expectations for full-year R&D expense. The Chimerix acquisition affects guidance in three ways. First, it will be accounted for as an asset acquisition. Consequently, we'll recognize a non-tax-deductible acquired IPR&D charge that we estimate will be between $870 million-$900 million. Second, we'll recognize Chimerix's results from operations from the date of close to the end of the year.

At a high level, this includes a non-material amount of revenue and cost of sales, as well as roughly $50 million in SG&A expenses and roughly $60 million in R&D expenses. Third, our interest expense and interest income expectations have been adjusted to reflect the timing of the net outlay for Chimerix, which was approximately $890 million, as well as the continued investment in Chimerix's operations over the remainder of the year. Moving to the Xyrem antitrust litigation settlements, our 2025 guidance has been updated to reflect the tax-deductible charge of $172 million that we recognized in our SG&A expenses in the 1st quarter. Finally, excluding Chimerix, our guidance has been adjusted to reflect a slightly lower R&D expense, roughly $20 million in aggregate, in our existing Jazz portfolio, driven primarily by the successful early conclusion of two phase IV Xywav studies.

Moving on to the slides that illustrate the specific revisions to our guidance, you'll see on slide 18 that we are affirming our full-year 2025 revenue guidance. Our guidance range remains $4.15 billion-$4.4 billion, which represents 5% year-over-year growth at the midpoint. This is driven by our confidence in both the neuroscience and oncology portfolios. Xywav continues to grow with impressive new patient adds and expansion of the IH market. We continue to expect Epidiolex will reach blockbuster status in 2025 and anticipate Rylaze revenues will normalize during the second quarter of 2025. We also believe Zepzelca's potential expansion into first-line maintenance therapy will provide more patients the ability to receive treatment for a longer duration. Turning to slide 19, our non-GAAP adjusted SG&A guidance range of $1.25 billion-$1.31 billion has been updated to $1.47 billion-$1.53 billion.

The revised range reflects the $172 million pre-tax charge booked this quarter associated with certain Xyrem antitrust litigation settlements and the addition of Chimerix. Our non-GAAP adjusted R&D guidance range of $720-$770 million has also been updated to $760-$1,100 million. This change is driven primarily by additional investment in ongoing clinical programs for dordaviprone, partially offset by the slight reduction in spend on the Jazz portfolio I mentioned earlier. On the bottom line, we expect adjusted net income to be $250-$350 million for the full year of 2025. The updated ANI guidance reflects the cumulative effect of all the items I described earlier. We're in a sound financial position with healthy cash flow generation over $400 million in the 1st quarter, and we have several near-term commercial opportunities and a particularly important upcoming data readout.

We continue to believe that a disciplined approach to capital allocation, including prioritized spend on our ongoing R&D programs and lead commercial products, as well as corporate development, will drive long-term shareholder value. I'll now turn the call back to Bruce for closing remarks.

Bruce Cozadd (CEO)

I'll conclude our prepared remarks on slide 21. We had a strong start to 2025 with continued focus on commercial execution led by growth of Xywav and Epidiolex and the ongoing launch of Zepzelca. In addition, we were pleased to close the Chimerix transaction and welcome our new colleagues as we work together to prepare for the potential launch of dordaviprone. Corporate development remains key to our strategy, and the Chimerix transaction is representative of our ability to identify and execute transactions that are strong strategic fits. dordaviprone is a potential near-term commercial opportunity with an efficient commercial call point and durable revenue stream. Our R&D pipeline continues to advance with the top-line PFS readout from our phase III GEA trial of zanidatamab expected in the second half of 2025, the near-term PDUFA date of dordaviprone in August, and the recent submission of the Zepzelca sNDA.

Our financial position, balance sheet, and cash flow generation remain strong, supported by our focus on operational excellence and strategic capital allocation. We remain well-positioned to continue delivering innovative therapies that transform the lives of patients and their families. That concludes our prepared remarks. I would now like to turn the call over to the operator to open the line for Q&A.

Operator (participant)

At this time, I would like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad. We kindly ask that you limit yourself to one question for today's call. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of Jason Gerberry of Bank of America. Please go ahead.

Jason Gerberry (Managing Director and Equity Research Analyst)

Hey, guys. Thanks for taking my question. I'm going to respect Phil's comment about not asking to speculate on tariffs, but what I'm going to ask is about your supply chain and specifically Xywave. You have a U.S. CDMO. I'm just curious if you can speak to Xywave is not a very high-volume product. Just curious to the extent that if need be, in 2026, you could fully supply the product from your U.S. CDMO. If you can comment if your API can be sourced in the U.S., such that you've got a fully U.S. supplied product for the U.S. market. Thanks.

Bruce Cozadd (CEO)

Yeah. Jason, thanks for the question. I appreciate your being respectful of the prior comments as well. We can comment on what we can and cannot. You are correct. We do have a U.S. supplier for Oxybate, including Xywave. That supplier does have enough capacity that we can access to fully meet our U.S. needs. Certainly, if tariffs are coming into play, it would be a very effective option for us to mitigate that exposure. There are no particular issues that I would note with regard to API and having that subject to tariff. All right. Go to the next caller, please.

Operator (participant)

Your next question comes from Jessica Fye with JPMorgan. Please go ahead.

Jessica Fye (Managing Director and Equity Research Analyst)

Hey, guys. Good afternoon. Thanks for taking my question. Following up on the first question, maybe thinking beyond Oxybate, can you talk about Jazz's manufacturing footprint, including sources of API and any other possible mitigation strategies or contingency plans to neutralize any potential impact of biopharma tariffs if they're implemented?

Bruce Cozadd (CEO)

Maybe I'll ask Renee to take the first part of that, which is just factually where we do our manufacturing. Then Phil, if you want to add anything more on tariffs, jump in.

Renee Gala (President and COO)

Sure, Bruce. And thanks for the question, Jess. So with respect to where we manufacture Xywav and Xyrem, Phil mentioned we do have a CMO in the U.S. We also have a facility in Athlone, Ireland. And so we do have a level of flexibility there. With respect to Epidiolex, we have a facility in the U.K. where we produce that product. And we have the capability to also develop other products at that plant. And then some of our other smaller products on the oncology side are manufactured in different locations. And Defitelio is in Villa Guardia, Italy. Vyxeos is manufactured by Simtra. And then Rylaze is manufactured in Denmark. So we do have quite a lot of manufacturing in Europe. In terms of our capabilities and what options we have going forward, obviously making changes to our manufacturing sources is something that we do not take lightly.

It does take a period of time. We do have a level of flexibility, as we mentioned today, with our Oxybate products. We will continue to evaluate both backup options and other sources of manufacturing. Phil?

Phil Johnson (CFO)

Yeah. No, it's a great summary. As you'd expect, Jess, this has been subject to quite a bit of work across the functional team since sort of late last year, early this year. There certainly are opportunities for us to work with CMOs here in the U.S. to further reduce the exposure to Jazz beyond those that we're currently working with. To date, the primary way that we've buffered impact would be through having sufficient inventory in market here in the U.S. to cover all or nearly all of our U.S. needs at this point for 2025 for each of our products. We'll continue with that strategy. Obviously, depending upon if and when tariffs come into effect, what geographies they would impact and what rate, we may have some protection for inventory for 2026 as well.

Turn it back to the operator for the next question, please.

Operator (participant)

Your next question comes from David Amsalem with Piper Sandler. Please go ahead.

David Amsalem (Managing Director and Senior Research Analyst)

Absolutely wanted to ask a question about Zepzelca and competition from In Delta. I know it's having an impact, and the label expansion is certainly not lost on me. I guess my question here is, how should we think about Zepzelca over time in terms of its trajectory? Do you anticipate that first-line contribution will overwhelm the pressure in the second-line setting? Also, how are you thinking about the expansion of In Delta itself, bearing in mind that Amgen has a pretty comprehensive development program in small cell lung in terms of earlier lines of therapy? How are you thinking about Zepzelca overall as a growth product going forward? Thanks.

Renee Gala (President and COO)

Yeah. I'm happy to jump in and take that one. As we think about Zepzelca, we did have some dynamics impacting the 1st quarter. As we look forward, though, to your point on Zepzelca returning to growth, even with competition and some delayed progression of first-line limited-stage patients coming into the second line, Zepzelca in the second line still remains the leading treatment as measured by market share. Importantly, we do look forward to both sharing our data at ASCO on the first-line and Forte trial, where we showed statistically significant and clinically meaningful PFS and OS in our study of first-line extensive-stage maintenance patients. This is something we look forward to presenting at ASCO and then rapidly submitting that data for potential inclusion in NCCN treatment guidelines. We do expect this data to be practice-changing.

Therefore, going into the first line, we look to a larger patient population to treat in the extensive-stage patients, but also longer treatment duration. We do expect this to contribute to future growth of the brand. We would also expect patients that did not receive Zepzelca in first line to have the opportunity to receive it in the second line. Rob, do you want to take the question with respect to the views of tarlatamab going forward from a clinical perspective?

Bruce Cozadd (CEO)

Yeah. Again, Jess, I think you covered it very well, Renee. With our new data and ultimately adoption into NCCN and in the label as first line, that affords us a larger population for a longer duration of therapy. tarlatamab's not approved in that setting. It would be quite a while before a new trial would read out there. I think that's the, as a new standard of care, I think that's the key that extensive-stage patients who don't progress after induction, as you said, should become the standard of care to get Zepzelca. For patients who don't receive it in front line, Zepzelca has data to show that it's an effective second-line therapy.

Operator (participant)

Your next question comes from Marc Goodman with Leerink Partners. Please go ahead.

Marc Goodman (Senior Research Analyst)

Phil, your comments about tariffs not impacting 2025, I assume have to do with the fact that you have inventory that you've just built up in the U.S. and so you don't have to worry about it. Is it a fair question to ask what would be the impact for a full year just on an annual basis if you didn't have all that inventory built up? What would we be talking about here as far as the numbers?

Phil Johnson (CFO)

Yeah. Marc, I appreciate the question. Sort of in this theoretical realm of what might happen in the future, it depends, obviously, on what kind of rates being put in, what kind of geographies are affected. We are not commenting at this point in time on those hypotheticals. I would say, again, depending on when tariffs would go into effect, if they are, we could get some coverage from inventory as we are getting effectively this year. We also have the ability for our Oxybate products to use U.S. source to effectively mitigate that exposure. Beyond that, the main tools available to us would be things like looking to work with other third-party manufacturers here in the U.S. to further reduce the impact. I feel very good about the position that we are in currently, obviously closely monitoring the situation, and we will take actions as needed.

Operator (participant)

Your next question comes from Andrea Flynn of Goldman Sachs. Please go ahead.

Hi, all. This is Telani on for Andrea. Thanks for taking our questions today. Would you want to understand a little bit better why does the Chimerix acquisition make sense for Jazz? And what do you find most compelling about the dordaviprone commercial opportunity? And related to that, how are you thinking about additional BD activities going forward? Thank you.

Bruce Cozadd (CEO)

Maybe I'll jump in at the total company acquisition level. Then Renee or Rob, if you want to add anything on dordaviprone in particular, you can. We've been, I think, pretty clear about our corporate development strategy for some time now as a major pillar of how we invest capital to create value for shareholders in addition to what we do in our investments in our commercial portfolio and in our R&D efforts. We've been clear that our priorities include finding products that would represent a real advance where there's unmet medical need in a serious condition that aligns with our capabilities, that has an efficient commercial call point so that we don't need to do a massive buildup of commercial expense, that have long durability.

We really feel that Chimerix on all fronts was a perfect fit for us, matches well with what we do well, particularly in oncology, near-term launch, again, efficient, and we're confident fills a serious unmet need. Rob, you want to jump in?

Rob Iannone (Executive VP and Chief Medical Officer)

Yeah. I'd love to. The treatment for diffuse glioma has not changed since I trained as a pediatric oncologist 25 years ago. Patients get debulking surgery, which is never curative, and then radiation therapy. That is essentially it. Prior to dordaviprone and prior to the discovery that H3 K27M mutations occurred and were a driver for oncogenesis in this setting, it has been shown now with dordaviprone that for patients with this mutation, the therapy is effective. We're really impressed with not only the efficacy, but also the safety profile in a disease setting, as I indicated, has an ongoing very high unmet need and without many other prospects, unfortunately.

Operator (participant)

Your next question comes from Annabel Samimy of Stifel. Please go ahead.

Annabel Samimy (Managing Director and Senior Analyst)

Hi. Thanks for taking my question. For Rylaze, I understand, obviously, that the protocols have changed for the pediatric indication that delays treatment. What can we expect for pickup in AYA? It's been, I guess, quite a little bit of time that you've been trying to drive growth in that area. When do you think we can get some critical mass there and some momentum to return Rylaze back to growth?

Bruce Cozadd (CEO)

Renee?

Renee Gala (President and COO)

Yeah. Thanks for the question there. With respect to the AYA segment, it really does take time to drive education with adult treaters to use asparaginase and Rylaze. These are treaters that often have a different protocol that they're following. We were certainly pleased last year with the updated results from the protocol that created the gap in asparaginase treatment because although it created a delay in when asparaginase is dosed, and it has led to some of the challenges that we've had with revenues, we feel very confident that it is demonstrating the importance of asparaginase to treatment. It has also resulted in much higher overall survival, which is good news for patients. We are having some momentum and success with respect to the AYA segment.

It does take a little bit more time than what we see in pediatrics, where we've had pretty much universal adoption. There has been some delay in getting back to that continued use. Importantly, as we've said before, there is no change to the total doses of asparaginase with the new protocol that is in place. We expect we will be getting back to normalization in the second quarter and can continue to focus on the growth in AYA.

Bruce Cozadd (CEO)

Maybe before we go to the next caller, I can just add something real quick. Annabelle, if you think about our oncology performance, particularly year-over-year, here in the 1st quarter, I think it's important to keep in mind what I've mentioned about there being one fewer shipping week effectively in the 1st quarter of this year. Obviously, it's hard to know when you have an additional week, are you getting that at an average rate, higher or lower, but just on pure math, missing one out of 13 is 7.7% or roughly 8% of the opportunity. Certainly, there was an impact on the year-over-year growth just given the fact that we had one fewer shipping day. Keep that in mind as you think about the trends and what you're seeing. Go to the next caller, please.

Operator (participant)

Your next question comes from Akash Tewari with Jefferies. Please go ahead.

Amy Li (SVP of Equity Research)

Hey, this is Amy on for Akash. Thanks so much for taking our question. Just one for HERIZON GEA. Would love to get your expectations on the control arm performance and what gives you confidence that Traz/Kemo isn't outperforming what was shown with KEYNOTE-811. Thanks so much.

Bruce Cozadd (CEO)

Rob?

Rob Iannone (Executive VP and Chief Medical Officer)

Yeah. As you know, there's been quite a bit of experience in this first-line HER2-positive GEA setting from the original TOGA trial that was the basis for the approval of Herceptin through the JACOB trial, and then more recently, KEYNOTE-811. Across those studies, the control arm of trastuzumab chemotherapy has performed pretty consistently with a median PFS between, I think, about 6.9 months up to a high of about 8.1 months in the more modern era. Through these three phase III trials, I think it gives us a pretty good idea of what to expect from the control arm. We planned accordingly. We continue to have confidence in zanidatamab's ability here. As you know, there have been two phase IIs published showing very promising results. zanidatamab with a median PFS of 15.2 months. That's the last publication. And zanidatamab/tezolizumab with a median PFS of 16.7 months.

At ASCO this year, we will update for the first time the overall survival data with zanidatamab. Prior to this, the median was not estimatable based on the maturity level. We look forward to presenting those data as well.

Operator (participant)

Your next question comes from Joseph Thome with TD Cowen. Please go ahead.

Joseph Thome (Managing Director and Senior Research Analyst)

Hey there. Good afternoon. Thank you for taking my question. On dordaviprone, I think Chimerix paused enrollment in the phase III study ahead of the acquisition. Kind of just curious if that has restarted and if you anticipate making any changes to the phase III trial in the first-line patients. Maybe relatedly, obviously, a lot of shakeups at the FDA. I guess, what kind of data points can you provide to make sure that everything is on track with the upcoming PDUFA date, especially given Chimerix did do a little bit of a 180 on the submission? Thank you.

Bruce Cozadd (CEO)

Rob?

Rob Iannone (Executive VP and Chief Medical Officer)

Yeah. Happy to take those. With regard to the FDA, so far, the review is going exactly as we expect. No surprises there and no indication that we would be off of our PDUFA date of August 18. The first part of your question was related to pausing enrollment in the ongoing confirmatory front-line trial. Just to clarify, that was paused only in the U.S. There, we were anticipating an approval and availability of drug and therefore would want to avoid the problem of patients enrolling and then crossing over from the control arm to get dordaviprone by prescription, which could confound the overall survival results. As you mentioned, while the trial is enrolling very well, we would have time potentially to make changes to the analysis plan.

We haven't announced any of those changes, but certainly, we'll look at that carefully to be sure that that trial is well-powered to deliver the results not only in a timely fashion, but that would be most informative.

Operator (participant)

Your next question comes from Gregory Renza with RBC Capital Markets. Please go ahead.

Gregory Renza (Director and Senior Analyst of Biotechnology Equity Research)

Hey, good evening, guys. Thanks for taking my question. My question is just on the Oxybates. As Renee, you were articulating just some effectiveness on the campaigns and how those are performing well. I just wanted to give you an opportunity to elaborate a little bit about what you're seeing and what the direct impacts are from the campaigns that have led to your reassurance about the contribution and the growth of the IH market. Thanks so much.

Renee Gala (President and COO)

Yeah. Thanks for the question. We are seeing beneficial response to the campaigns. We're seeing, as we are building in particular the idiopathic hypersomnia market, we are seeing our disease education and continued interactions with physicians helping them to better identify idiopathic hypersomnia. It also helps patients to better understand this condition for which there has not been a lot of disease awareness in the past because without an approved medication, there's not a lot of incentive to actually diagnose someone with idiopathic hypersomnia. Not only have we had good success with the digital and media campaigns that I mentioned, but we've continued to sharpen our execution in the field. We have continued to grow new prescribers. We've had great success with our field nurse educator program. We've had a number of other initiatives that are proving effective and really give us confidence in the growth.

If you look at where we ended this quarter, this 1st quarter of 2025, and compare that to where we were a year ago, stepping out of the 1st quarter of 2024, looking at the patient ads, we've seen an increase of 5%. That is in a mature market with competition, which is really great progress. With idiopathic hypersomnia, we've had an increase of 39% looking at the progress over the last 12 months. We are really excited about the continued momentum that we have. Certainly, we have seasonality each year in the 1st quarter, but still executing really well in this area.

Operator (participant)

Your next question comes from Joel Beatty with Baird. Please go ahead.

Joel Beatty (Biotechnology Equity Research Analyst)

Hi. Thanks for taking the question. I'm Doran Pravon. Could you discuss a little bit more about where it could fit in the treatment algorithm initially upon approval? Also, when could the 1st results come from the action trial that might affect how it's used?

Bruce Cozadd (CEO)

Rob?

Rob Iannone (Executive VP and Chief Medical Officer)

Yeah. We expect, based on the submission that we've made, we expect the initial accelerated approval to be in the recurrent setting. The action trial, as you know, is treating in the front-line setting after patients receive debulking surgery and radiation therapy. That would give us an opportunity to expand to the front line. We haven't given specific dates on when that would read out, but we have said it's enrolling to plan.

Operator (participant)

Your next question comes from Ami Fadia with Needham. Please go ahead.

Ami Fadia (Senior Analyst)

Hi, everyone. Thanks for taking my question. Can you provide us with an update on JZP-441, where you are with the NT1 study and when we might get an update on that? Just more broadly, touching upon the comments previously around business development, have your priorities changed or evolved in the last couple of months as we've seen the market change? If you could sort of comment on what types of assets, whether it's by the therapeutic area or the stage of development you'd be focused on as you think about adding something inorganically. Thank you.

Bruce Cozadd (CEO)

I'm just going to remind people, try to limit it to one question. On this one, maybe Rob, you could talk about 441. Phil, if you want to jump in on corporate development priorities.

Rob Iannone (Executive VP and Chief Medical Officer)

Yeah. We have initiated the 441 trial, which I'll remind you is intended to be in a small number, approximately 10 patients with NT1. And we expect to look at those data as they come in, but we haven't given any specific guidance on when we would share information on those data just as yet.

Phil Johnson (CFO)

Yeah. The nominee on—I'm sorry. Let me finish up with the second part of the question. For corporate development, priorities are unchanged. We continue to look at corporate development as a very important way for us to go ahead and reach more patients over time and create value for shareholders. We finished the 1st quarter in a really strong financial position with $2.6 billion in cash investments, $430 million in operating cash flow in the quarter. Even after the payment of roughly $890 million net to acquire Chimerix, we're in a really strong position to continue to invest in our future. We do look across the various therapeutic areas that we're currently in, as well as selectively at other rare orphan diseases where we can deploy our capabilities to create value.

We do look at both licensing, like we did very successfully with the licensing deal with Zymworks that has brought us, obviously, zanidatamab. And then obviously, look for acquisitions like we've done. We think very successfully looking forward to the upcoming PDUFA and then hopefully launch right thereafter of dordaviprone. We continue to be active in looking at opportunities, see a number of them we think that would make sense for us across our various therapeutic areas. I would expect to see us continue to be active in this area. I would say on the margin, the uncertainty that's created by some of the tariff and other policy discussions does not change fundamentally what we're looking to do.

Bruce Cozadd (CEO)

Probably on the margin means that we'll want to take a slightly more conservative capital structure stance, maybe keeping a bit more cash than we might otherwise, and maybe not fully using all of the potential debt capacity that we have, but still able to use a significant portion of that to advance our corporate development efforts. Hopefully that gives you some context. If we can go to the next caller, please.

Operator (participant)

Your next question comes from Ashwani Verma of UBS. Excuse me. Please go ahead.

Ashwani Verma (Stock Analyst)

Hi. Yeah. Thanks for taking my question. I just wanted to clarify. I think you mentioned that one less week of ordering. Is that for a handful of products, or which products is it for, or is it across the business?

Bruce Cozadd (CEO)

Yes. That would have been across our U.S. oncology business and common for the various products there. Renee, anything you want to add?

Renee Gala (President and COO)

Nope. That's correct.

Your next question comes from Mohit Bansal with Wells Fargo. Please go ahead.

Mohit Bansal (Managing Director)

Good. Thank you for taking my question. I have a question for you, Rob. In our conversation with some breast cancer doctors, the interesting takeaway was that it is not a hormone confusion that an HER2 would become 1st-line agent for all the HER2-positive patients. Likely, part of it is safety and comfort with the Cleopatra regimen. The question is, do you see a potential for Zanni to be the 1st line as well? What kind of trials you may have to do there? Cleopatra is a really long regimen here. Thank you.

Bruce Cozadd (CEO)

Sure. I mean, I would just reinforce our primary strategy, which is to position after an HER2 because of the data we've generated showing activity of zanidatamab, very promising activity after just about any prior and even multiple different HER2 agents, including standard front-line therapy, which is Herceptin, Perjeta, and chemo, and HER2, TDM1, Tucatinib, etc. Positioning it after an HER2, which is currently second line and likely to move to front line for, I would say, a great majority of patients in this disease setting is really very meaningful. There will not be any other HER2 therapies that will have been evaluated in that particular setting. Remember, these patients tend to go on to get multiple lines of therapy.

You're right that there would be a few, there would be some patients who may not tolerate an HER2 or would have some pre-existing condition that would prevent them from. I think in those cases, a patient who's either progressed on or intolerant to an HER2 could move on to zanidatamab based on the 303 trial. If an HER2 is ultimately approved in the front-line setting, I do think it will be the great majority of patients who get it based on the strong efficacy.

Operator (participant)

Your next question comes from Sean Laaman of Morgan Stanley. Please go ahead.

Mike Riad (Biotech Equity Research)

Hi. This is Mike Riad on for Sean Lallman. Thank you for taking our question. For Xywav and narcolepsy, are you able to provide a more granular breakout for patients needing oxybate versus high-sodium switches? In IH, how are you thinking about Xywav's value proposition with potential for a competitive threat there from the MRIs? Thank you.

Bruce Cozadd (CEO)

Renee?

Renee Gala (President and COO)

Yeah. With respect to the narcolepsy ads, we have seen primarily ads in the quarter coming from new to Oxybate patients. I think that does speak to what we're now starting to see, which is a bit of an expansion to the market given that this is a more mature product. We've been really pleased with what we're seeing in terms of both field execution, the appreciation of low sodium to physicians and also to patients. That's really resonating. It's clear that HCPs and patients are prioritizing long-term health benefits of low sodium as well as the dosing flexibility that Xywav offers. We do see switching to or shifting over to IH. We do see IH as the area where there's the most opportunity to drive growth.

With respect to any future potential competition in IH from Lumrise, I would say, again, Xywav is the only low-sodium option. We do know from the data that we have been able to generate, we know that narcolepsy and IH patients are at increased risk for cardiovascular comorbidities relative to the general population. We do continue to see all high-sodium oxybate patients as potential Xywav patients. Keep in mind that within our label for Xywav for idiopathic hypersomnia, there is flexible dosing. That indication is twice nightly or once nightly, depending on what the physician and the patients choose to pursue in terms of their therapy. We feel we are quite well positioned with respect to narcolepsy and idiopathic hypersomnia.

Bruce Cozadd (CEO)

I will also just jump in and point out that for those of you that saw the court decision today, given that our IP has been found to be valid, that Avadel has admitted to infringing it, we still do not see, even after today's ruling, a viable path for Avadel to commercialize Lumryz in IH before the expiration of the relevant patent in 2036. I totally agree with everything Renee said in terms of potential competitive positioning and differences between the product. There is some room to go before we actually do have competition in IH.

Operator (participant)

Your next question comes from Gary Nachman with Raymond James. Please go ahead.

Gary Nachman (Managing Director)

Thanks, and good afternoon. For zanidatamab and BTC, understanding it's a small indication, how is the ramp going? How rapid is the penetration? What's the anecdotal feedback on how the drug is performing? Have there been any challenges with access and how you're helping facilitate that? If GEA ends up being positive in first line as a bigger market, would you consider changes to pricing at all? Also, how would your promotional efforts change for that indication versus BTC? Thanks.

Renee Gala (President and COO)

Yeah. Thanks for the question. We had our first patients treated in December shortly after launch for VTC. The reception has been quite positive. HCPs are glad to have Zyhera available to treat patients. Just as a reminder, VTC is a very small patient population, 3,000 patients in the U.S. in first line and second line. Therefore, we do expect revenues from this first indication, as we've stated, to be quite modest. In terms of access, we haven't really had any issues. What we're in the process of doing is ensuring we've spent quite a lot of time in these first few months ensuring that we have agreements and the necessary logistics in place for community and academic centers to be able to get access to the product rapidly.

Certainly, the efficacy supporting this approval is something that they're excited to be able to bring to patients. When we look at GEA, we're excited to be able to read out that study in the second half. With that data and with publication of that data, we would intend to go rapidly towards, again, trying to get NCCN guidelines in place similar to what we intend to do relative to Zepzelca. Of course, we would not promote without having an approval, but having the product on NCCN guidelines will enable use for that indication should physicians choose to do so. I think with respect to pricing, we're in a good position. We typically will comment on pricing when we have a launch/approval. Stay tuned. We think given the benefit that we are seeing in efficacy, we'll be in a good position where we are today.

Operator (participant)

Your next question comes from Charles Duncan with Cantor Fitzgerald. Please go ahead.

I'm for Charles. Thank you for taking our questions. You reiterated confidence in Epidiolex reaching blockbuster status in 2025. Can you speak about any catalysts or what market dynamics underpin that expectation? Also, can you talk about any meaningful in the U.S. or in off-label usage that could contribute to this trajectory? Thank you.

Bruce Cozadd (CEO)

Yeah. Renee?

Renee Gala (President and COO)

Yeah. I didn't hear the full question, but what I understood was one of the.

Bruce Cozadd (CEO)

Yeah. I can jump in on the first part, Renee, and just say our confidence that it remains on track for blockbuster status is in part driven by it's already at that run rate and has been continuing to grow, as you saw with the 10% first quarter over first quarter growth. Renee, you can comment on where growth can be coming from, but we're very solidly on track.

Renee Gala (President and COO)

Yeah. Thanks, Bruce. The call had cut out for me. We are quite confident in where we're going with respect to the future. Epidiolex is a highly differentiated product within the ASM landscape. We have a robust body of evidence supporting that both on the seizure side as well as the non-seizure benefits. That data continues to resonate with physicians and caregivers, in particular on the non-seizure benefits side: cognition, behavior, emotional, and social function. Also, the broad spectrum efficacy and well-characterized safety profile enables physicians to have Epidiolex combine well with other agents, which is particularly important in this area given polypharmacy. While we do not promote off-label, we do see the product used across a number of different epilepsy subtypes across the underlying seizures for which we've shown efficacy.

In terms of additional growth, we're having great momentum in the adult and long-term care setting. We have a new screening tool that we've put into that we've launched and additional initiatives to help identify LGS, for example, in previously undiagnosed patients in the adult setting. Our access has been high quality and continues to improve. With respect to our nurse navigator program, we're seeing strong persistency and seeing that even become stronger with respect to the nurse navigator program helping to guide patients through starting therapy. All of those elements give us confidence in the overall growth. The durability we've talked about having settled with our Andaphilers, we think we're in an excellent position there as well.

Operator (participant)

Your final question comes from Julie with Truist Securities. Please go ahead.

Joon Lee (Managing Director and Senior Biotech Analyst)

Hey. Thanks for squeezing me in. For the HERIZON GEA, are you able to comment on the ratio of patients who are PD-1 positives? I mean, is the ratio closer to what we saw in KEYNOTE-811 or closer to your phase I/II Zani plus chemo plus Tisley study? Thank you.

Bruce Cozadd (CEO)

I don't have that information. I just would remind you that how you characterize positive depends a little bit on which assay you're using, etc. We are measuring it, and we'll have the ability to look at that post-hoc as needed to support regulatory approval.

Operator (participant)

That will conclude our question-and-answer session. I will now turn the call back over to Chairman and Chief Executive Officer Bruce Cozadd for closing remarks.

Bruce Cozadd (CEO)

Thank you, Operator. Let me just say with Epidiolex and Xywav growth, some upcoming exciting approvals on the oncology side of our business across three different products and GEA data upcoming. There's a lot to look forward to. I'd just like to close today's call by recognizing our Jazz colleagues for their efforts and thanking our partners and shareholders for their continued confidence and support. Thank you all for joining us today.

Operator (participant)

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.