Q1 2025 Jazz Pharmaceuticals PLC Earnings Call

May 6, 2025

To the jazz Pharmaceuticals first quarter 2025 webcast conference call.

Operator: I would like to welcome everyone to the Jazz Pharmaceuticals Q1 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 1 on your telephone keypad. If you would like to withdraw your question, press star 1 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 Macdonald. Please go ahead.

All lines have been placed on mute to prevent any background noise. After the speakers' 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.

Speaker Change: I would now like to turn the call over to executive director of Investor Relations, Jeff Mcdonald. Please go ahead.

Rob Iannone: If the Phase 3 trial findings are positive, we expect the data will support registration based on potentially clinically meaningful PFS and supportive OF data. Three data map presentations have been accepted at ASCO, including updated overall survival data from the phase two first-line GEA trial. In addition, there will be an oral presentation on the safety and efficacy of DERDAVA.

Speaker Change: Thank you operator, and good afternoon, everyone today Jazz Pharmaceuticals reported its first quarter 2025 financial results.

Jeff Macdonald: Thank you, operator, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its Q1 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 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 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.

Speaker Change: Slide presentation accompanying this webcast is available on the investors section of our website.

Speaker Change: You should also refer to the press release, we issued earlier today that is available on our website on.

Tiffany: 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.

On the call today are Bruce <unk>, Chairman and Chief Executive Officer, Renee Gala, President and Chief Operating Officer, Rob you known Executive Vice President Global head of R&D, and Chief Medical Officer until Johnson, Chief Financial Officer.

Rob Iannone: Turning to neuroscience, we recently initiated our planned Phase 1b trial to evaluate the efficacy, safety, tolerability, and pharmacokinetics of JZP441 in participants with type 1 narcolepsy. And 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 analysis. We observe numeric improvements in both the primary and several secondary. and we remain on track to meet with the Japanese health authorities in mid 2025.

Speaker Change: On slide two I would 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.

Speaker Change: We encourage you to review the statements contained in today's press release, and our slide deck and the risks and uncertainties described under the caption risk factors in our annual report on Form 10-K for the fiscal year ended December 31, 2024, and our subsequent filings with the SEC, including our quarterly report on Form 10-Q for the finance.

Jeff Macdonald: 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 caption "Risk Factors" in our annual report on Form 10-K for the fiscal year ended 31 December 2024, and our subsequent filings with the SEC, including our quarterly report on Form 10-Q for the financial quarter ended 31 March 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 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 investor section of our website.

Rob Iannone: As outlined on slide 14, Standard Data Map has proven to be a unique, differentiated, and highly effective dual-targeted HER2 therapy. DataDataMap provides opportunities across multiple HER2-positive solid tumors and represents a global opportunity for Jazz in multiple markets.

Speaker Change: 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.

Speaker Change: We undertake no duty or obligation to update our forward looking statements.

Speaker Change: 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 investors section of our website.

Rob Iannone: Following the FDA approval of Xanadatamab in second line BTC last year, the CHMP recently adopted a positive opinion, recommending the marketing authorization of Xanadatamab 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.

Bruce: I'll now turn the call over to Bruce.

Bruce: Thanks, Jeff Good afternoon, everyone. Thank you for joining us today to discuss <unk> first quarter 2025 results I'll start on slide five.

Jeff Macdonald: I'll now turn the call over to Bruce.

Bruce Cozadd: 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 Ziihera in advanced HER2-positive biliary tract cancer, or BTC, in the European Union. In addition, the acquisition of Kymerix has further strengthened our presence in rare oncology. On the commercial front, we generated $898 million in total revenues across our portfolio.

Bruce: <unk> 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 or.

Rob Iannone: We have also completed recruitment for our Phase 3 trial, evaluating the metadata map and first-line GEA, and expect top-line PFS data later this year. The overall development program for ZanaDataMap includes multiple registration-enabling trials, including pivotal trials in first-line BTC, first-line GEA, Advanced Breast Cancer, and in a Pant Tumor Basket Trial, focused on areas where we believe Xyme has the potential to emerge as the preferred HER2-targeted therapy. This comprehensive development program underscores our confidence in ZetaDataMaps' potential.

Bruce: Our focus on execution and operational excellence.

Bruce: <unk> solid commercial performance led by up of dialects and sideways and significant progress across our R&D pipeline.

Bruce: We submitted a supplemental new drug application or SMA, two expands up sell into first line maintenance in extensive stage small cell lung cancer and received a positive <unk> opinion recommending marketing authorization of presenting data mab and advanced her two positive biliary tract cancer.

Bruce: Or BTC in the European Union.

Rob Iannone: Turning to slide 15, we are also very excited that the Chimerix transaction has been completed.

In addition, the acquisition of <unk> has further strengthened our presence in railroad oncology.

Rob Iannone: I'm thrilled to welcome our new colleagues to Our team is now engaged and working toward the shared goal of delivering Drodaviprone to patients. Dodaviprone is a groundbreaking first-in-class small molecule in development for H3K27M mutant diffuse glial. 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 H3K27M mutant diffuse glioma, both as monotherapy. and in combination with other treatment approaches including radiation with a consistently favorable safety profile.

Bruce: On the commercial front, we generated 898 million in total revenues across our portfolio.

Bruce: Our neuroscience portfolio had a strong start to the year with <unk> 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 epidiorite demand as revenues increased 10.

Bruce Cozadd: 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 US, and Ziihera advanced BTC in Europe. Moving to R&D, we're advancing promising opportunities in our pipeline. The HERIZON-GEA-01 Phase III trial evaluating Ziihera in first-line gastroesophageal adenocarcinoma, or GEA, remains on track to read out in the second half of this year.

Percent year over year, and we remain confident in its blockbuster potential.

Bruce: While we experienced near term headwinds with certain oncology products, our oncology portfolio is poised for growth with three potential regulatory approvals in the coming months, including <unk> <unk> expansion in the first line maintenance therapy in the U S and zany data Mab advanced DTC in Europe.

Bruce: Moving to R&D, we are advancing promising opportunities in our pipeline.

Rob Iannone: The FDA has accepted an NDA for dordaviprone, seeking accelerated approval for treatment of H3K27M mutant diffusoglioma in adult and pediatric patients. Progressive Disease Following Prior Therapy. The application has been granted priority review and assigned a PDUFA target action date of August 18th 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.

Bruce: The horizon <unk>, one phase III trial evaluating any data Mab and first line gastroesophageal adenocarcinoma or gea remains on track to read out in the second half of this year we.

Bruce: We continue to progress other key is any data mab clinical trials, including the phase III empower BC 303 trial in breast cancer.

Bruce Cozadd: We continue to progress other key zanidatamab clinical trials, including the Phase III Empower BC303 trial in breast cancer. We're looking forward to sharing important data on Zepzelca, zanidatamab, and dordaviprone at ASCO in June. We added dordaviprone to our pipeline through the Kymerix 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 Kymerix acquisition and litigation settlement charges.

Bruce: We're looking forward to sharing important data on <unk> is there any data at <unk> at <unk> in June.

Bruce: We added <unk> to our pipeline through the <unk> 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.

Rob Iannone: Beyond the Recurrent Disease Setting, dordataprone is being studied in the ongoing phase three action trial. Evaluating its use in newly diagnosed H3K27M mutant diffuse glioma patients following radiation treatment. This trial has the potential to confirm the clinical benefit of dordataprone in recurrent H3K27M mutant diffuse glioma and potentially extend this treatment option into the frontline setting. We believe that dordaviprone has the potential to transform the standard of care for this underserved patient population with very limited treatment options.

Bruce: Given its patent protection into 2037 with possible extensions and the potential for expanded use in the frontline setting we view <unk> as a meaningful and durable revenue opportunity for jobs.

Bruce: 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.

Bruce: We remain confident in our topline revenue guidance and have updated our financial guidance to include the recent <unk> acquisition and litigation settlement charges.

Phil Johnson: Now I will turn the call over to Phil for a financial update. Phil? 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 10-Q, which will be filed tomorrow morning. In the first quarter of 2025, we recorded $898 million in total revenue. I'll note, our first quarter revenues have historically been affected by several factors, including reauthorizations and inventory built in the latter part of the prior year, which typically burns off in the first half of the following year.

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

Bruce Cozadd: 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?

Bruce: <unk>.

Thanks, Chris I'll begin on slide seven to discuss the continued progress of our commercial portfolio, starting with our sleep therapeutic area.

Renée Galá: Thanks, Bruce. I'll begin on slide 7 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 Q1 2025. Xywav net product sales were approximately $345 million in the first 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.

Renee Gala: Thanks, Bruce. I'll begin on slide 7 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 Q1 2025. Xywav net product sales were approximately $345 million in the first 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.

Bruce: I am pleased to report total revenue for sleep, which includes <unk> xyrem net product sales plus royalties from high sodium oxidate authorized generics or Ags was approximately $431 million in the first quarter of 2025.

Phil Johnson: As Rene mentioned, throughout the dialects, we saw more of this burn in the first quarter this year. Despite these factors, Xywave and Epidiolex revenues grew 9% and 10% year-over-year respectively. Our oncology products experienced a decline relative to the first quarter of 2024. In part, this was driven by having one fewer shipping week in the first quarter of 2025 compared to the first quarter of 2024. In addition, the decline was primarily driven by our two largest oncology products, Zepselka and Rylase. As Renee noted earlier, we believe we have line of sight into a resumption of growth for these products in the coming quarter.

Bruce: <unk> net product sales were approximately $345 million in the first quarter, an increase of 9% year over year.

Bruce: As a reminder, we typically see seasonality in our sleep revenue due to re authorizations at the beginning of each year.

Bruce: Might be expected seasonality <unk> had a robust quarter of patient as driven by strong execution from the field teams and we continue to be excited about the direction of our sleep portfolio.

Bruce: There were approximately 14600 active <unk> patients exiting the first quarter, representing an increase of approximately 450 net patient adds compared to the fourth quarter of 2024 comprised of 125 narcolepsy patients and 325 IAA.

Renée Galá: There were approximately 14,600 active Xywav patients exiting Q1, representing an increase of approximately 450 net patient adds compared to Q4 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 Xywav is the first 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.

Renee Gala: There were approximately 14,600 active Xywav patients exiting Q1, representing an increase of approximately 450 net patient adds compared to Q4 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 Xywav is the first 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.

Phil Johnson: As I will highlight on the next slide, we are affirming our total revenue guidance for 2025 based on our conviction and the strength of our overall commercial portfolio. Adjusted net income and earnings per share in the first quarter of this year were impacted by charge related to certain Xyrom antitrust litigation settlements. This $172 million charge to SG&A in the first 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.

Bruce: <unk> patients.

Bruce: Narcolepsy patient adds consisted predominantly of oxalate naive patients along with patients transitioning from high <unk> debates our efforts to educate on the importance of reducing sodium intake and the increased risk of cardiovascular comorbidities among narcolepsy patients continue to <unk>.

Phil Johnson: 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 any indirect impact resulting in inflation on goods we purchased 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 US at some hypothetical rate.

Bruce: Resonate with Hcp's and with patients.

Bruce: We see the most opportunity for patient growth from the IH market, whereas the <unk> is the first 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.

Bruce: <unk> 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 HCP.

Renée Galá: 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 and Epidiolex, Epidiolex had net product sales of approximately $218 million in Q1, a 10% increase year-over-year. Growth was primarily driven by underlying demand and, to a lesser extent, favorable US payer mix, partially offset by US inventory burn. Exiting Q1, inventory was lower than we would typically see at this time of the year.

Renee Gala: 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 and Epidiolex, Epidiolex had net product sales of approximately $218 million in Q1, a 10% increase year-over-year. Growth was primarily driven by underlying demand and, to a lesser extent, favorable US payer mix, partially offset by US inventory burn. Exiting Q1, inventory was lower than we would typically see at this time of the year.

Bruce: 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.

Phil Johnson: 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 we have sufficient inventory in the US to serve all or nearly all of our 2025 needs for each of our products. Consequently, we expect that any impact to our 2025 financials would be de minimis, if any, and unlikely to affect our guidance.

Bruce: Turning to slide eight in Napa dialects at the dialects had net product sales of approximately $218 million in the first quarter.

Speaker Change: Narcolepsy patient adds consisted predominantly of oxidate naive patients along with patients transitioning from high <unk> to base, our efforts to educate on the importance of reducing sodium intake and the increased risk of cardiovascular comorbidities among narcolepsy patients continue to rise.

Bruce: 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 first quarter inventory was lower than we would typically see at this time of the year, our <unk> commercial and <unk>.

Phil Johnson: With that context, let's move to our updated 2025 financial diagram. 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 chimerics acquisition, certain Xyram antitrust litigation settlements, and slightly revised expectations for full year R&D expense. The Chimerics Acquisition effects 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 and $900 million. Second, we'll recognize Chimerics' results from operations from the date of close to the end of the year.

Speaker Change: Nate with Hcp's and with patients.

Speaker Change: You see the most opportunity for patient growth from the IH market, whereas the <unk> the first and only FDA approved therapy as we continue to build this market disease education on the benefits of using a nighttime therapy.

Bruce: <unk> teams have been executing well with key drivers of demand growth in the U S. Including continued data generation on the benefits of at the dialects beyond seizure control expanded reach to adult patients in long term care facilities, along with broad quality access and the nurse Navigator program, where.

Renée Galá: Our Epidiolex commercial and medical teams have been executing well, with key drivers of demand growth in the US 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 9, Rylaze net product sales were approximately $94 million in Q1 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.

Renee Gala: Our Epidiolex commercial and medical teams have been executing well, with key drivers of demand growth in the US 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 9, Rylaze net product sales were approximately $94 million in Q1 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.

Speaker Change: Dress sleep inertia, and sometimes 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 HCP.

Bruce: Pleased with the growth about the dialects and expect it to reach blockbuster status in 2025.

Bruce: Moving to oncology on slide nine <unk> net product sales were approximately $94 million in the first quarter of 2025, a decrease of 8% year over year.

Speaker Change: These campaigns are performing well contributing to the growth of the IH markets and we continue to enhance our field effectiveness to optimize our impact for patients.

Phil Johnson: 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 Xyron 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 first quarter.

Bruce: As we previously noted <unk> 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.

Speaker Change: Turning to slide eight Napa dialects at the dialects had net product sales of approximately $218 million in the first quarter, a 10% increase year over year.

Speaker Change: Growth was primarily driven by underlying demand and to a lesser extent favorable U S payer mix, partially offset by U S inventory burn.

Bruce: Based on feedback from Kols about their expected use of asparaginase, we continue to see the impact to relates as temporary with revenue normalizes. During the second quarter of 2025, we are making steady progress in the adolescent and young adult market and continue to view that as the greatest opportunity for <unk>.

Renée Galá: 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 Q2 2025. We are making steady progress in the adolescent and young adult market and continue to view that as the greatest opportunity for growth for Rylaze. Turning to slide 10, net product sales for Zepzelca in Q1 2025 were approximately $63 million, a decrease of 16% year-over-year. First-quarter revenue was impacted by increased competition in the second-line setting. In addition, there has been increased adoption of an immunotherapy regimen for the treatment of first-line limited-stage small cell lung cancer. This is delaying patient progression to second-line treatment.

Renee Gala: 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 Q2 2025. We are making steady progress in the adolescent and young adult market and continue to view that as the greatest opportunity for growth for Rylaze. Turning to slide 10, net product sales for Zepzelca in Q1 2025 were approximately $63 million, a decrease of 16% year-over-year. First-quarter revenue was impacted by increased competition in the second-line setting. In addition, there has been increased adoption of an immunotherapy regimen for the treatment of first-line limited-stage small cell lung cancer. This is delaying patient progression to second-line treatment.

Speaker Change: In the first quarter inventory was lower than we would typically see at this time of the year.

Speaker Change: At the dialects 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 at the dialects beyond seizure control expanded reach to adult patients in long term care facilities, along with broad quality access and the nurse navigator.

Bruce: <unk>.

Phil Johnson: Finally, excluding chimerics, our guidance has been adjusted to reflect 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 Xi-Wave 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 to $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. Xywave continues to grow with impressive new patient ads and expansion of the IH market.

Bruce: Turning to slide 10, net product sales for <unk> in the first quarter of 2025 were approximately $63 million.

Kris: Kris a 16% year over year first quarter revenue was impacted by increased competition in the second line setting. In addition, there has been increased adoption of an immunotherapy regimen for the treatment of first line limited stage small cell lung cancer. This is delaying patient progression to second line.

Program.

Speaker Change: We're pleased with the growth about the dialects and expect it to reach blockbuster status in 2025.

Speaker Change: Moving to oncology on slide nine <unk> net product sales were approximately $94 million in the first quarter of 2025, a decrease of 8% year over year as.

Bruce: Treatment.

Bruce: <unk> remains the leading treatment in second line small cell lung cancer based on market share and we're excited about the opportunity to expand into first line maintenance therapy for extensive stage small cell lung cancer, which we expect would place <unk> back on a growth trajectory.

Renée Galá: Zepzelca remains the leading treatment in second-line small cell lung cancer based on market share, and we're excited about the opportunity to expand into first-line maintenance therapy for extensive-stage small cell lung cancer, which we expect would place Zepzelca back on a growth trajectory. Moving to slide 11 and our ongoing Ziihera launch. In December of last year, FDA approved Ziihera, the first and only dual HER2-targeted bispecific antibody approved for HER2-positive second-line BTC in the US. We recognized approximately $2 million of net product sales in Q1 2025. While it's early in the 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.

Renee Gala: Zepzelca remains the leading treatment in second-line small cell lung cancer based on market share, and we're excited about the opportunity to expand into first-line maintenance therapy for extensive-stage small cell lung cancer, which we expect would place Zepzelca back on a growth trajectory. Moving to slide 11 and our ongoing Ziihera launch. In December of last year, FDA approved Ziihera, the first and only dual HER2-targeted bispecific antibody approved for HER2-positive second-line BTC in the US. We recognized approximately $2 million of net product sales in Q1 2025. While it's early in the 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.

Speaker Change: As we previously noted <unk> 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.

Phil Johnson: We continue to expect that the dialects will reach blockbuster status in 2025 and anticipate Riley's revenues will normalize during the second quarter of 2025. We also believe that Psilco'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-gas adjusted SG&A guidance range of $1.25 to $1.31 billion has been updated to $1.47 to $1.53 billion. The revised range reflects the $172 million pre-tax charge booked this quarter associated with certain Xyram antitrust litigation settlements and the addition of Chimera. Our non-gas-adjusted R&D guidance range of $720 to $770 million has also been updated to $760 to $110 million.

Bruce: Moving to slide 11, and our ongoing Sahara launch in December of last year, FDA approves that HERA, the first and only dual her two targeted by specific antibody approved for her two positive second line BTC in the U S. We recognized approximately $2 million of net product sales in the first quarter of 2020.

Speaker Change: Based on feedback from Kols about their expected use of asparaginase, we continue to see the impact to relates as temporary with revenue normalized during the second quarter of 2025, we are making steady progress in the adolescent and young adult market and continue to view that as the greatest opportunity for <unk>.

Speaker Change: For Riley's.

Bruce: While.

Bruce: While it's early in the launch reception from Hcp's has been positive. We are hearing initial customer experiences are aligned with the clinical profile, we observed in clinical trials.

Speaker Change: Turning to slide 10, net product sales for <unk> in the first quarter of 2025 were approximately $63 million a decrease of 16% year over year first quarter revenue was impacted by increased competition in the second line setting. In addition, there has been increased adoption of it.

Bruce: As a reminder, DTC as a rare disease with a limited number of patients and we expect revenue contribution to be modest from this rare cancer.

Speaker Change: No therapy regimen for the treatment of first line limited stage small cell lung cancer. This is delaying patient progression to second line treatment does.

Bruce: We expect this initial launch in second line her two positive BTC will help us to establish <unk> as a best in class for two targeted therapy that demonstrate significant benefit for patients. In addition, the BTC approval helps health care professionals gained meaningful experience with <unk> prior.

Renée Galá: We expect this initial launch in second-line HER2-positive BTC will help us to establish Ziihera as a best-in-class HER2-targeted therapy that demonstrates significant benefit for patients. In addition, the BTC approval helps healthcare professionals gain meaningful experience with Ziihera 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?

Renee Gala: We expect this initial launch in second-line HER2-positive BTC will help us to establish Ziihera as a best-in-class HER2-targeted therapy that demonstrates significant benefit for patients. In addition, the BTC approval helps healthcare professionals gain meaningful experience with Ziihera 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?

Phil Johnson: This change is driven primarily by additional investment in ongoing clinical programs for dardaviprone, 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 to $350 million for the full year of 2020. 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 first 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.

Speaker Change: <unk> remains the leading treatment in second line small cell lung cancer based on market share and we're excited about the opportunity to expand into first line maintenance therapy for extensive stage small cell lung cancer, which we expect would place <unk> back on a growth trajectory.

Rob: Two as a potential indication and gea I will now turn it over to Rob for an update on our pipeline and upcoming milestones Rob.

Speaker Change: Moving to slide 11, and our ongoing Sahara launch in December of last year, FDA approves that HERA, the first and only dual her two targeted by specific antibody approved for her two positive second line BTC in the U S. We recognized approximately $2 million of net product sales in the first quarter of 2020.

Thanks, Renee I'll begin on slide 13.

Robert Iannone: 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 IMforte 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, 2 June. Presentation in a peer-reviewed form also enables us to submit the data for potential inclusion in NCCN guidelines and compendium listing.

Rob Iannone: 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 IMforte 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, 2 June. Presentation in a peer-reviewed form also enables us to submit the data for potential inclusion in NCCN guidelines and compendium listing.

Rob: I am excited about our pipeline and the significant progress we have made on key programs with additional milestones expected this year.

Rob: Looking first at oncology.

Rob: We completed the submission of an <unk> to FDA to expand the ZIP Selco label to include maintenance therapy to first line extensive stage small cell lung cancer for patients who have not progressed during induction chemotherapy.

Speaker Change: While it's early in the launch reception from Hcp's has been positive. We are hearing initial customer experiences are aligned with the clinical profile, we observed in clinical trials.

Bruce Cozadd: I'll now turn the call back to Bruce for closing remarks. 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 Zywave and Epidiolex and the ongoing launch of Zyhera. 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 Dordatapron. 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. Dordatapron is a potential near-term commercial opportunity with an efficient commercial call point and durable revenue stream.

Rob: The submission is based on a statistically significant and clinically meaningful progression free survival or PFS.

As a reminder, DTC as a rare disease with a limited number of patients and we expect revenue contribution to be modest from this rare cancer.

Rob: And overall survival or OS data from the phase III <unk> trial of <unk>.

We expect this initial launch in second line her two positive BTC will help us to establish <unk> as a best in class for <unk>.

Rob: In combination with <unk> compared to a seasonal listen envelope.

Eric.

Significant benefit for patients. In addition, the BTC approval helps health care professionals gained meaningful experience with <unk> prior to a potential indication and gea I will now turn it over to Rob for an update on our pipeline and upcoming milestones Rob.

Rob: The results have the potential to be practice changing and.

Rob: And we look forward to showcasing the data in an oral presentation at <unk> on Monday June 2nd.

Rob: Presentation in a peer reviewed forum also enables us to submit the data for potential inclusion in <unk>.

Rob: CCN guidelines and companion listing.

Thanks, Renee I'll begin on slide 13.

Bruce Cozadd: Our R&D pipeline continues to advance with the top line PFS readout from our Phase 3 GEA trial of ZanyDatamap expected in the second half of 2025, the near-term PDUFA date of Dordatapron in August, and the recent submission of the ZepZelka 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.

Rob: We also remain on track for topline readout of PFS data from the Horizon GE <unk> trial in the second half of this year.

I am excited about our pipeline and the significant progress we have made on key programs with additional milestones expected this year.

Robert Iannone: 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.

Rob Iannone: 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.

Rob: First interim analysis of OS.

Looking first at oncology.

We completed the submission of an <unk> to FDA to expand the <unk> label to include maintenance therapy to first line extensive stage small cell lung cancer for patients who have not progressed during induction chemotherapy.

Rob: Also occur at this time.

Rob: We are encouraged by the positive results from two independent phase III trials of <unk> in first line Gea the demonstrated increased median PFS.

The submission is based on a statistically significant and clinically meaningful progression free survival or PFS.

Rob: <unk> response.

Rob: And confirmed objective response rates.

Rob: The phase III trial signings are positive we expect the data will support registration based on potentially clinically meaningful PFS and supportive OS data three.

And overall survival or OS data from the phase III <unk> trial of <unk>.

Bruce Cozadd: That concludes our prepared remarks.

Operator: I would now like to turn the call over to the operator to open the line for Q&A. 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.

In combination with <unk> compared to a seasonal listen envelope.

Rob: <unk> added data Mab presentations have been accepted at <unk>, including updated overall survival data from the phase III first line <unk> trial.

The results have the potential to be practice change and.

And we look forward to showcasing the data in an oral presentation at <unk> on Monday June 2nd.

Rob: In addition, there will be an oral presentation on the safety and efficacy of <unk> from <unk>.

Presentation in a peer reviewed forum also enables us to submit the data for potential inclusion to end CCN guidelines and companion listing.

Rob: Turning to neuroscience, we recently initiated our planned phase <unk> trial to evaluate the efficacy safety Tolerability and pharmacokinetics of GBP 441 in participants with type one narcolepsy.

Jason Gerberry: Your first question comes from the line of Jason Gerberry of Bank of America. Please go ahead. Hey guys, thanks for taking my question.

Robert Iannone: Turning to neuroscience, we recently initiated our planned Phase 1B trial to evaluate the efficacy, safety, tolerability, and pharmacokinetics of JZP441 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 observe 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.

Rob Iannone: Turning to neuroscience, we recently initiated our planned Phase 1B trial to evaluate the efficacy, safety, tolerability, and pharmacokinetics of JZP441 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 observe 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.

We also remain on track for top line readout of PFS data from the Horizon GE <unk> trial in the second half of this year.

Renee Gala: And so 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 Zywave. So you have a US CDMO. And so I'm just curious, you know, if you can speak to, Zywave is not a very high volume product. So I'm just curious to the extent that, you know, if need be, in 2026, you could, you know, fully supply the product from your US CDMO. And if you can comment, if you're API can be sourced in the US such that you've got a fully US supplied product for the US market.

Rob: And with respect to our <unk> trial in Japan, we.

First interim analysis of OS will also occur at this time.

Rob: We are continuing to collect long term safety data, which was included in the trial design for 26% and 52 week analysis.

We are encouraged by the positive results from two independent phase II trials of <unk> in first line Gea the demonstrated increased median PFS.

Rob: We observe numeric improvements in both the primary and several secondary endpoints.

Rob: And we remain on track to meet with the Japanese health authorities in mid 2025.

<unk> of response.

Confirmed objective response rates.

Rob: As outlined on slide 14.

If the phase III trial signings are positive we expect the data will support registration based on potentially clinically meaningful PFS and supportive OS data.

Rob: <unk> has proven to be a unique differentiated and highly effective tool targeted her to therapy.

Renee Gala: Thanks.

Renee Gala: Jason, thanks for the question, and I appreciate your being respectful of the prior comments as well, and we can comment on what we can. So, you're correct, we do have a U.S. supplier for Oxibate, including ZyWave. That supplier does have enough capacity that we can access to fully meet our U.S. needs. And certainly, if tariffs are coming into play, it would be a very effective option for us to mitigate that exposure. And there's no particular issues that I would note with regard to API and having that subject to tariffs.

Rob: <unk> provides opportunities across multiple her two positive solid tumors.

<unk> added data Mab presentations have been accepted at <unk>, including updated overall survival data from the phase III first line Gea trial.

Rob: And represents a global opportunity for jazz and multiple markets.

Rob: Following the FDA approval of <unk> in second line DTC last year.

In addition, there will be an oral presentation on the safety and efficacy of their data from.

Robert Iannone: 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 3 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.

Rob Iannone: 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 3 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.

Rob: <unk> recently adopted a positive opinion recommending the marketing authorization of <unk> for the treatment of adults with previously treated unresectable locally advanced or metastatic her two positive BTC.

Turning to neuroscience, we recently initiated our planned phase <unk> trial to evaluate the efficacy safety Tolerability and pharmacokinetics of GBP 441 in participants with type one narcolepsy.

Rob: 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.

And with respect to our epic dialects trial in Japan, we.

Operator: Operator, go to the next caller, please.

Jessica Fye: Your next question comes from Jessica Fye with J.P. Morgan. Please go ahead. Hey guys, good afternoon. Thanks for taking my question.

We are continuing to collect long term safety data, which was included in the trial design for 26% and 52 week analysis.

Rob: We have also completed recruitment for our phase III trial evaluating data Mab and first line gea.

Renee Gala: So following up on the first question, maybe thinking beyond OxyBait, can you talk about Jazz's manufacturing footprint, including sources of API? And, you know, any other possible mitigation strategies or contingency plans to, you know, neutralize any potential impact of biopharma tariffs if they're implemented?

We observe numeric improvements in both the primary and several secondary endpoints.

Rob: <unk> top line PFS data later this year.

Rob: The overall development program presented data map includes multiple registration, enabling trials, including pivotal trials in first line BTC.

And we remain on track to meet with the Japanese health authorities in mid 2025.

As outlined on slide 14 seven.

Rob: First line Gea.

<unk> has proven to be a unique differentiated and highly effective tool targeted her to therapy.

Rob: Advanced breast cancer and in a pan tumor basket trial.

Rob: Focused on areas, where we believe <unk> has the potential to emerge as the preferred her to targeted therapy.

Renee Gala: Maybe I'll ask Renee to take the first part of that, which is just factually where we do our manufacturing. And then, Phil, if you want to add anything more on tariffs, jump in. Sure, Bruce, and thanks for the question, Jeff. So with respect to where we manufacture Zywave and Zyrem, 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.

<unk> provides opportunities across multiple her two positive solid tumors.

And represents a global opportunity for jazz and multiple markets.

Rob: This comprehensive development program underscores our confidence in <unk> potential.

Following the FDA approval of <unk> in second line DTC last year.

Rob: Turning to slide 15, we are also very excited that the <unk> transaction has been completed.

Robert Iannone: Turning to slide 15, we are also very excited that the Kymerix 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 H3K27M mutant diffuse 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 H3K27M mutant diffuse glioma, both as monotherapy and in combination with other treatment approaches, including radiation, with a consistently favorable safety profile.

Rob Iannone: Turning to slide 15, we are also very excited that the Kymerix 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 H3K27M mutant diffuse 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 H3K27M mutant diffuse glioma, both as monotherapy and in combination with other treatment approaches, including radiation, with a consistently favorable safety profile.

<unk> recently adopted a positive opinion recommending marketing authorization of salmon data man for the treatment of adults with previously treated unresectable locally advanced or metastatic her two positive BTC.

Rob: And thrilled to welcome our new colleagues to jazz.

Rob: Our team is now engaged and working towards a shared goal of delivering <unk> to patients.

Rob: So <unk> is a groundbreaking first in class small molecule in development for <unk>, three K 27, <unk> mutant glioma.

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.

A rare high grade brain tumor.

We have also completed recruitment for our phase III trial evaluating <unk> in first line gea.

Rob: Commonly affects children and young adults.

Renee Gala: And then some of our other smaller products on the oncology side are manufactured in different locations, and Depotilio is in Villa Guardia, Italy. Vixios is manufactured by Syntra, and then Rylase is manufactured in Denmark. So we do have quite a lot of manufacturing in Europe.

Rob: Currently no approved drug therapies for these patients.

<unk> top line PFS data later this year.

Rob: And the median overall survival from diagnosis is approximately only one year.

The overall development program presented to date and that includes multiple registration, enabling trials, including pivotal trials in first line BTC.

Rob: Multiple clinical studies have demonstrated <unk> benefit in patients with recurrent <unk> three K 27, diffuse glioma, both as monotherapy.

First line Gea.

Advanced breast cancer and in a pan tumor basket trial.

Renee Gala: In terms of our capabilities and what options we have going forward, obviously making changes to our manufacturing sources is something that we don't take lightly. It does take a period of time, but we do have a level of flexibility, as we mentioned today, with our Oxivate products, and we'll continue to evaluate both backup options and other sources of manufacturing.

Rob: And in combination with other treatment approaches, including radiation with a consistently favorable safety profile.

Focused on areas, where we believe <unk> has the potential to emerge as the preferred <unk> targeted therapy.

Rob: The FDA has accepted an NDA for <unk>.

This comprehensive development program underscores our confidence in diamond data maps potential.

Robert Iannone: The FDA has accepted an NDA for dordaviprone, seeking accelerated approval for treatment of H3K27M-mutant diffuse 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, 2025. 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 3 action trial, evaluating its use in newly diagnosed H3K27M-mutant diffuse glioma patients following radiation treatment. This trial has the potential to confirm the clinical benefit of dordaviprone in recurrent H3K27M-mutant diffuse glioma and potentially extend this treatment option into the front-line setting.

Rob Iannone: The FDA has accepted an NDA for dordaviprone, seeking accelerated approval for treatment of H3K27M-mutant diffuse 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, 2025. 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 3 action trial, evaluating its use in newly diagnosed H3K27M-mutant diffuse glioma patients following radiation treatment. This trial has the potential to confirm the clinical benefit of dordaviprone in recurrent H3K27M-mutant diffuse glioma and potentially extend this treatment option into the front-line setting.

Rob: David prone seeking accelerated approval for treatment of H, three K 27, <unk> mutant glioma and adult and pediatric patients.

On to Slide 15, we are also very excited that the <unk> transaction has been completed.

Rob: Progressive disease following prior therapy the.

I am thrilled to welcome our new colleagues to jazz.

Rob: The application has been granted priority review.

Our team is now engaged and working towards a shared goal of delivering through <unk> patients.

Rob: And assigned a <unk> target action date.

Phil Johnson: Phil? Yeah, no, it's a great summary, and as you'd expect, Jess, this has been subject of quite a bit of work across a cross-functional team since sort of late last year, early this year. And 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, sort of 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.

Rob: 18th of this year.

So <unk> is a groundbreaking first in class small molecule in development for <unk>, three K 27 diffuse gliomas.

Rob: On communication with the FDA to date.

Rob: We do not expect the agency to hold an oncology drug Advisory Committee meeting in connection with the review of the NDA.

A rare high grade brain tumor.

Rob: Beyond the recurrent disease setting towards <unk> is being studied in the ongoing phase III action trial.

Commonly affects children and young adults.

Currently no approved drug therapies for these patients.

Rob: Evaluating its use in newly diagnosed <unk> three K 2700, <unk> mutant <unk>.

The median overall survival from diagnosis is approximately only one year.

Rob: Few scleroma patients following radiation treatment.

Multiple clinical studies have demonstrated <unk> benefit to patients with recurrent <unk> three K 27, and you can do.

This trial has the potential to confirm the clinical benefit of <unk> and recurrent age three 8-K 27.

Diffused glaucoma, both as monotherapy.

In combination with other treatment approaches, including radiation with a consistently favorable safety profile.

Rob: A few scleroma and potentially extend this treatment option into the frontline setting.

Phil Johnson: We'll continue with that strategy, then obviously, depending upon if and when tariffs come into effect, what geographies they would impact and what rate, we may have some protection from inventory for 2026 as well.

Rob: We believe that <unk> has the potential to transform the standard of care for this underserved patient population with very limited treatment options.

The FDA has accepted an NDA or <unk> seeking accelerated approval for treatment of H, three K 27, <unk> mutant glioma, and adult and pediatric patients with progressive disease. Following prior therapy.

Robert Iannone: 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?

Rob Iannone: 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?

Rob: Now I will turn the call over to Phil for a financial update Bill.

David Amsellem: Your next question comes from David Amsellem with Piper Sandler. Please go ahead. I actually wanted to ask a question about ZepZelka and competition in Delta. I know it's having an impact and the label expansion is certainly not lost on me, but I guess my question here is, you know, how should we think about ZepZelka over time in terms of its trajectory? Do you anticipate that first line contribution will overwhelm the pressure in the second line setting?

Phil: Thanks, Rob.

The application has been granted priority review and assigned a <unk> target action date.

Phil: 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 10-Q, which will be filed tomorrow morning, and the first quarter 2025, we recorded $898 million in total revenues.

Philip Johnson: 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 10-Q, which will be filed tomorrow morning. In the first quarter of 2025, we recorded $898 million in total revenues. I'll note our first 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 first half of the following year. As Renee mentioned, for Epidiolex, we saw more of this burn in the first quarter of this year. Despite these factors, Xywav and Epidiolex revenues grew 9% and 10% year-over-year, respectively. Our oncology product experienced a decline relative to the first quarter of 2024.

Phil Johnson: 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 10-Q, which will be filed tomorrow morning. In the first quarter of 2025, we recorded $898 million in total revenues. I'll note our first 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 first half of the following year. As Renee mentioned, for Epidiolex, we saw more of this burn in the first quarter of this year. Despite these factors, Xywav and Epidiolex revenues grew 9% and 10% year-over-year, respectively. Our oncology product experienced a decline relative to the first quarter of 2024.

<unk> 18th of this year.

On communication with the FDA today.

We do not expect the agency to hold an oncology drug Advisory Committee meeting in connection with the review of the NDA.

Phil: Note, our first quarter revenues have historically been affected by several factors, including reauthorization and inventory build in the latter part of the prior year, which typically burns off in the first half of the following year.

Beyond the recurrent disease setting <unk> is being studied in the ongoing phase III <unk> trial.

Evaluating its use in newly diagnosed H three K 27, <unk> mutant glioma patients following radiation treatment.

Speaker Change: Now you mentioned throughout the dialogues we saw more of this burn in the first quarter of this year despite.

Speaker Change: Despite these factors skywave and dialogues revenues grew 9% and 10% year over year, respectively.

David Amsellem: And then 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? So how are you thinking about ZepZelka overall as a growth product going forward? Thank you.

This trial has the potential to confirm the clinical benefit of <unk> and recurrent age three 8-K 27.

Speaker Change: Our oncology products experienced a decline relative to the first quarter of 2024 and.

A few Scully Homer and potentially extend this treatment option into the frontline setting.

Speaker Change: In part this is driven by having one fewer shipping week in the first quarter of 2025 compared to the first quarter of 2024.

Philip Johnson: In part, this was driven by having one fewer shipping week in Q1 2025 compared to Q1 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 a resumption of growth for these products in the coming quarters. As I will 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 Q1 of this year were impacted by a charge related to certain Xyrem antitrust litigation settlements.

Phil Johnson: In part, this was driven by having one fewer shipping week in Q1 2025 compared to Q1 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 a resumption of growth for these products in the coming quarters. As I will 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 Q1 of this year were impacted by a charge related to certain Xyrem antitrust litigation settlements.

We believe that <unk> has the potential to transform the standard of care for this underserved patient population with very limited treatment options.

Speaker Change: In addition, the decline was primarily driven by our two largest oncology products <unk> and <unk> as Renee noted earlier, we believe we have line of sight into a resumption of growth for these products in the coming quarters.

Renee Gala: Yeah, I'm happy to jump in and take that one. So as we think about Zepfelka, we did have some dynamics impacting the first quarter. As we look forward, though, to your point on Zepfelka returning to growth, even with competition and some delayed progression of first line limited stage patients coming into the second line, Zepfelka in the second line still remains the leading treatment as measured by market share.

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

Speaker Change: As I will 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.

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 10-Q, which will be filed tomorrow morning, and the first quarter of 2025, we recorded $898 million in total revenues.

Adjusted net income and earnings per share in the first quarter of this year impacted by a charge related to certain xyrem antitrust litigation settlements.

Speaker Change: This $172 million charge to SG&A in the first quarter reduced our adjusted net income by $146 million and our GAAP and non-GAAP EPS of $2 38 per share and $2 34 per share respectively.

Philip Johnson: This $172 million charge to SG&A in Q1 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 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 US at some hypothetical rate.

Phil Johnson: This $172 million charge to SG&A in Q1 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 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 US at some hypothetical rate.

Note, our first quarter revenues have historically been affected by several factors, including reauthorization and inventory built in the latter part of the prior year, which typically burns off in the first half of the following year.

Renee Gala: Importantly, we do look forward to both sharing our data at ASCO on the first line and 4K trial, where we showed StatFig and clinically meaningful PFS and OS in our study of first line extensive stage maintenance patients. And so this is something we look forward to presenting at ASCO and then rapidly submitting that data for potential inclusion in NCC and treatment guidelines. We do expect this data to be practice changing and 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.

And I mentioned from a dialogue we saw more of this firm in the first quarter of this year. Despite.

Speaker Change: Before discussing our updated 2025 financial guidance I'd like to comment on tariffs.

Despite these factors <unk> revenues grew 9% and 10% year over year, respectively.

Speaker Change: 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.

Our oncology products experienced a decline relative to the first quarter of 2024 and.

Speaker Change: I'll start with the tariffs already enacted on China, Mexico, and Canada, as well as the general 10% tariff levied more broadly.

In part this is driven by having one fewer shipping week in the first quarter of 2025 compared to the first quarter of 2024.

Speaker Change: For 2025.

Speaker Change: No direct financial impact from these tariffs and currently expect any indirect impact resulting in inflation on goods, we purchase can be managed within our existing internal budgets and external guidance.

In addition, the decline was primarily driven by our two largest oncology products <unk> and <unk> as it remain noted earlier, we believe we have line of sight into a resumption of growth for these products in the coming quarters.

Rob Iannone: So we do expect this to contribute to future growth of the brand. And we would also expect patients that didn't receive Zepfelka in first line to have the opportunity to receive it in the second line.

Speaker Change: We won't speculate on the potential impact of future tariffs on pharmaceutical products imported into the U S. At some hypothetical right.

With that 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.

Speaker Change: As you'd expect we've evaluated various scenarios.

Philip Johnson: 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 US to serve all or nearly all of our 2025 needs for each of our products. Consequently, we expect that any impact to 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 Kymerix acquisition, certain Xyrem antitrust litigation settlements, and slightly revised expectations for full-year R&D expense. The Kymerix acquisition affects guidance in three ways. First, it will be accounted for as an asset acquisition.

Phil Johnson: 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 US to serve all or nearly all of our 2025 needs for each of our products. Consequently, we expect that any impact to 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 Kymerix acquisition, certain Xyrem antitrust litigation settlements, and slightly revised expectations for full-year R&D expense. The Kymerix acquisition affects guidance in three ways. First, it will be accounted for as an asset acquisition.

The net income and earnings per share in the first quarter of this year.

Positioned to comment in a timely manner, if and when such tariffs are enacted.

<unk> <unk> charge related to certain Xyrem antitrust litigation settlements.

Rob Iannone: And then, Rob, do you want to take the question with respect to the views of Tarlatumab going forward from a clinical perspective? Yeah, again, Jess, I think you've covered it very well, Rene. 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. Trilatomab is not approved in that setting. and it would be quite a while before a new trial would read out there. So I think that's the, you know, that 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 Subzelka.

Speaker Change: 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.

$172 million charge to SG&A in the first quarter reduced our adjusted net income by $146 million and our GAAP and non-GAAP EPS of $2 38 per share and $2 34 per share respectively.

Speaker Change: Consequently, we expect that any impact for 2025 financials will be de minimis, if any and unlikely to affect our guidance.

With that context, let's move to our updated 2025 financial guidance.

Before discussing our updated 2025 financial guidance I'd like to comment on tariffs 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.

Speaker Change: Now at first glance the update may seem complex.

Speaker Change: In reality there are three drivers for the updates and I think you'll find there are pretty straightforward.

Speaker Change: Those three drivers are the <unk> acquisition.

I'll start with the tariffs already enacted on China, Mexico, and Canada as well as the general 10% tariff levied more broadly for.

Speaker Change: Certain xyrem antitrust litigation settlements and slightly revised expectations for full year R&D expense.

For 2025, we anticipate no direct financial impact from these tariffs.

Speaker Change: The <unk> acquisition guidance in three ways.

Speaker Change: First it will be accounted for as an asset acquisition.

Currently expect any indirect impact resulting in inflation on goods purchased can be managed within our existing internal budgets and external guidance.

Speaker Change: Consequently, we will recognize a non tax deductible acquired IP R&D charge, we estimate will be between $870 and $900 million.

Philip Johnson: Consequently, we'll recognize a non-tax deductible acquired IPR&D charge that we estimate will be between $870 and $900 million. Second, we'll recognize Kymerix'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 Kymerix, which was approximately $890 million, as well as the continued investment in Kymerix'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 recognize in our SG&A expenses in Q1.

Phil Johnson: Consequently, we'll recognize a non-tax deductible acquired IPR&D charge that we estimate will be between $870 and $900 million. Second, we'll recognize Kymerix'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 Kymerix, which was approximately $890 million, as well as the continued investment in Kymerix'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 recognize in our SG&A expenses in Q1.

Rob Iannone: And then for patients who don't receive it in front line, Subzelka, you know, has data to show that it's an effective second line therapy.

We won't speculate on the potential impact of future tariffs on pharmaceutical products imported into the U S. At some hypothetical right.

Speaker Change: Second we're recognized <unk> results from operations from the date of close to the end of the year.

Have you expect we've evaluated various scenarios and are positioned to comment in a timely manner, if and when such tariffs are enacted.

Speaker Change: At a high level. This includes a non material amount of revenue and cost of sales as well as roughly $50 million and SG&A expenses, and roughly $60 million and R&D expenses.

Mark Goodman: Your next question comes from Mark Goodman with Lering Partners. Please go ahead.

We have sufficient inventory in the U S to serve all or nearly all of our 2025 needs for each of our products.

Phil Johnson: 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. But is it a fair question to ask, what would be the impact for a full year, just on an annual basis, if you did have all that inventory built up? Like, what would we be talking about here as far as the numbers?

Speaker Change: Third our interest expense and interest income expectations have been adjusted to reflect the timing of the net outlay for <unk>, which was approximately $890 million.

Consequently, we expect that any impact to our 2025 financials will be de minimis, if any and unlikely to affect our guidance.

With that context.

Speaker Change: As well as the continued investment in <unk> operations over the remainder of the year.

Let's move to our updated 2025 financial guidance.

Now at first glance, the update may seem complex in.

Speaker Change: Moving to the Xyrem Anti Trust litigation settlements or 2025 guidance has been updated to reflect the tax deductible charge of $172 million.

In reality there are three drivers for the updates and I think you'll find there are pretty straightforward.

Phil Johnson: Yeah, Mark, appreciate the question. Sort of in the 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. So we're not commenting in 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're getting effectively this year. And then we also have the ability for our Oxibate 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.

Key drivers are the <unk> acquisition.

Speaker Change: Recognized in our SG&A expenses in the first quarter.

Certain xyrem antitrust litigation settlements and slightly revised expectations for full year R&D expense.

Speaker Change: Finally, excluding <unk> our guidance has been adjusted to reflect a slightly lower R&D expense roughly $20 million in aggregate in our existing Jeff's portfolio driven primarily by the successful early conclusion of two phase <unk> studies.

Philip Johnson: Finally, excluding Kymerix, our guidance has been adjusted to reflect 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 to $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 Q2 2025.

Phil Johnson: Finally, excluding Kymerix, our guidance has been adjusted to reflect 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 to $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 Q2 2025.

<unk> acquisition of FX guidance in three ways.

First it will be accounted for as an asset acquisition.

Consequently, we will recognize a non tax deductible acquired IP R&D charge that we estimate will be between $870 and $900 million.

Speaker Change: 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 or.

We're recognized <unk> results from operations data close to the end of the year.

Speaker Change: Our guidance range remains for one 5% to $4 4 billion.

Speaker Change: Which represents 5% year over year growth at the midpoint.

At a high level. This includes a non material amount of revenue and cost of sales as well as roughly $50 million and SG&A expenses, and roughly $60 million and R&D expenses.

Speaker Change: This was driven by our confidence in both the neuroscience and oncology portfolios.

Phil Johnson: to further reduce the impact. But I feel very good about the position that we're in currently. Obviously, closely monitoring the situation, we'll take actions as needed.

Speaker Change: <unk> continues to grow with impressive new patient adds and expansion of the Iot market.

Third our interest expense and interest income expectations have been adjusted to reflect the timing of the net outlay for <unk>, which was approximately $890 million.

Speaker Change: We continue to expect that the dialectical reached blockbuster status in 2025, and anticipate wireless revenues will normalize during the second quarter of 2025.

Andrea Newkirk: Your next question comes from Andrea Newkirk of Goldman Sachs. Please go ahead. Hi all, this is Talani on for Andrea. Thanks for taking our questions today.

As well as the continued investment in <unk> operations over the remainder of the year.

Speaker Change: We also believe that silke as potential expansion in the first line maintenance therapy will provide more patients the ability to receive treatment for longer duration.

Philip Johnson: 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 to 1.31 billion has been updated to $1.47 to 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 Kymerix. Our non-GAAP adjusted R&D guidance range of $720 to 770 million has also been updated to $760 to 110 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 to 350 million for the full year of 2025.

Phil Johnson: 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 to 1.31 billion has been updated to $1.47 to 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 Kymerix. Our non-GAAP adjusted R&D guidance range of $720 to 770 million has also been updated to $760 to 110 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 to 350 million for the full year of 2025.

Moving to the Xyrem Anti Trust litigation settlements or 2025 guidance has been updated to reflect the tax deductible charge of $172 million will be recognized in our SG&A expenses in the first quarter.

Bruce Cozadd: Would you want to understand a little bit better, why does the Chimax acquisition make sense for Jazz, and what do you find most compelling about the Dordava Pro and commercial opportunity? And related to that, how are you thinking about additional BD activities going forward? Thank you.

Speaker Change: Turning to slide 19, our non-GAAP adjusted SG&A guidance range of one to 513 1 billion.

Finally, excluding <unk> 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 <unk> studies.

Speaker Change: It's been updated to $1 47 to $1 five.

Rob Iannone: So maybe I'll jump in at the total company acquisition level and then And we've been clear that our priorities include finding products that would represent, you know, 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, you know, a massive build up of commercial expense that have long durability. and we really feel that Chimerics 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.

Speaker Change: $3 billion.

Speaker Change: The revised range reflects the $172 million pre tax charge booked this quarter associated with certain Xyrem antitrust litigation settlement and the addition of <unk>.

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.

Speaker Change: Our non-GAAP adjusted R&D guidance range of $720 million to $770 million has also been updated to $760 million to $110 million.

Our guidance range remains for one 5% to $4 4 billion.

This change is driven primarily by additional investment in ongoing clinical programs for <unk>, partially offset by the slight reduction in spend on the jazz portfolio I mentioned earlier.

Which represents 5% year over year growth at the midpoint. This.

This was driven by our confidence in both the neuroscience and oncology portfolios.

Speaker Change: On the bottom line, we expect adjusted net income to be $250 million to $350 million for the full year of 2025.

It continues to grow with impressive new patient adds and expansion of the EIS market.

We continue to expect that the dialectical reached blockbuster status in 2025, and anticipate wireless revenues will normalize during the second quarter of 2025.

Speaker Change: We updated Eni guidance reflects the cumulative effect of all the items I described earlier.

Philip Johnson: The updated A&I 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 Q1, 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.

Phil Johnson: The updated A&I 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 Q1, 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.

Speaker Change: We are in a sound financial position with healthy cash flow generation, we're $400 million in the first quarter and we have several near term commercial opportunities and are particularly important upcoming data readout.

We also believe that silke as potential expansion in the first line maintenance therapy will provide more patients the ability to receive treatment for a longer duration.

Speaker Change: We do believe that a disciplined approach to capital allocation.

Turning to slide 19, our non-GAAP adjusted SG&A guidance range of one to 513 1 billion.

Speaker Change: <unk> prioritize spend on our ongoing R&D programs and lead commercial products as well as corporate development will drive long term shareholder value.

The updated to $1 47 to $1 five 3 billion.

The revised range reflects the $172 million pre tax charge booked this quarter associated with certain Xyrem antitrust litigation settlement and the addition of <unk>.

I will now turn the call back to Bruce for closing remarks.

Speaker Change: I'll conclude our prepared remarks on slide 21.

Bruce Cozadd: 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 Ziihera. In addition, we were pleased to close the Kymerix 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 Kymerix 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.

Speaker Change: We had a strong start to 2025 with continued focus on commercial execution led by growth of <unk> and the ongoing launch of XI era.

Rob Iannone: Rob, you want to jump in? Yeah, I'd love to. You know, the treatment for diffuse glioma hasn't changed since I trained as a pediatric oncologist 25 years ago. Patients get debulking surgery, which is never curative, and then radiation therapy. And that's essentially it. Prior to dordaviprone and prior to the discovery that H3K27M mutations occurred and were a driver for oncogenesis in this setting, it's 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 they indicated, has an ongoing very high unmet need and without many other prospects, unfortunately.

Our non-GAAP adjusted R&D guidance range of $720 million to $770 million has also been updated to $760 million to $110 million.

Speaker Change: In addition, we were pleased to close the <unk> transaction and welcome our new colleagues as we work together to prepare for the potential launch of tornado prone.

This change is driven primarily by additional investment in ongoing clinical programs for <unk>, partially offset by the slight reduction in spend on the SaaS portfolio I mentioned earlier.

Corporate development remains key to our strategy and the <unk> transaction is representative of our ability to identify and execute transactions that are strong strategic fits <unk> as a potential near term commercial opportunity with an efficient commercial call point and durable revenue stream.

On the bottom line, we expect adjusted net income to be $250 million to $350 million for the full year of 2025, we.

We updated Eni guidance reflects the cumulative effect of all the items I described earlier.

We're in a sound financial position with healthy cash flow generation, we're $400 million in the first quarter and we have several near term commercial opportunities and are particularly important upcoming data readout.

Speaker Change: Our R&D pipeline continues to advance with the top line PFS readout from our phase III <unk> trial Zany data may have expected in the second half of 2025, the near term <unk> data at <unk> in August and the recent submission of the <unk> NDA.

We do believe that a disciplined approach to capital allocation.

<unk> prioritize spend on our ongoing R&D programs and lead commercial products as well as corporate development will drive long term shareholder value.

Speaker Change: Our financial position balance sheet and cash flow generation remained 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.

Bruce Cozadd: 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.

I'll now turn the call back to Bruce for closing remarks.

Annabel Samimy: Your next question comes from Annabel Samimy of Stifle, please go ahead. Hi, thanks for taking my question. So for Ryleigh's, I understand, obviously, that the protocols have changed for the pediatric indication that delays treatment. But 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. And when do you think we can get some critical mass there and some momentum to return Ryleigh's back to growth?

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 <unk> and the ongoing launch of XI era.

Speaker Change: That concludes our prepared remarks, I would now like to turn the call over to the operator to open the line for Q&A.

In addition, we were pleased to close the <unk> transaction and welcome our new colleagues as we work together to prepare for the potential launch of <unk>.

Speaker Change: 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 currently 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.

Operator: 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.

Corporate development remains key to our strategy and the <unk> transaction is representative of our ability to identify and execute transactions that are strong strategic fit for <unk> as a potential near term commercial opportunity with an efficient commercial call point and durable revenue stream.

Renee Gala: Rene? 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 Rylase. These are treaters that often have a different protocol that they're following, and so 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, and it's also resulted in much higher overall survival, which is good news for patients.

Speaker Change: Your first question comes from the line of Jason <unk> of Bank of America. Please go ahead.

Our R&D pipeline continues to advance with the topline PFS readout from our phase III <unk> trial zany data may have expected in the second half of 2025, the near term <unk> data at <unk> in August and the recent submission of the <unk> NDA.

Speaker Change: Hey, guys. Thanks for taking my question.

[Analyst]: Hey, guys. Thanks for taking my question. And so 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 Xywav. So you have a US CDMO, and so I'm just curious if you can speak to Xywav is not a very high-volume product, so just curious to the extent that if need be, in 2026, you could fully supply the product from your US CDMO. And if you can comment if your API can be sourced in the US such that you've got a fully US-supplied product for the US market. Thanks.

Jason Gerberry: Hey, guys. Thanks for taking my question. And so 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 Xywav. So you have a US CDMO, and so I'm just curious if you can speak to Xywav is not a very high-volume product, so just curious to the extent that if need be, in 2026, you could fully supply the product from your US CDMO. And if you can comment if your API can be sourced in the US such that you've got a fully US-supplied product for the US market. Thanks.

Speaker Change: So I'm gonna respect Phils comment about not asking you to speculate on tariffs, but what I'm going to ask is about your supply chain.

Speaker Change: Typically it's <unk>. So you have a U S CMO and so I'm just curious if you can speak to <unk> got a very high volume product. So.

Our financial position balance sheet and cash flow generation remained 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.

Speaker Change: Just curious to the extent that if.

Speaker Change: If need be and 2026, you could fully supply the product from your U S. C demo and if you can comment if your API can be sourced in the U S. Such that you've got a fully U S supply product for the U S market. Thanks.

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

Speaker Change: Yes, Jason Thanks for the question.

Bruce Cozadd: Yeah. Jason, thanks for the question, and I appreciate your being respectful of the prior comments as well. We can comment on what we can't. So you're correct. We do have a US supplier for oxybate, including Xywav. That supplier does have enough capacity that we can access to fully meet our US needs. And certainly, if tariffs are coming into play, it would be a very effective option for us to mitigate that exposure. And there's no particular issues that I would note with regard to API and having that subject to tariff. Operator, go to the next caller, please.

Speaker Change: I appreciate your being respectful of the prior comments is what we can comment on what we can.

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.

Speaker Change: So you are correct, we do have a U S supplier for <unk>, including XI wave.

Renee Gala: But 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, but there has been some delay in getting back to that continued use.

Speaker Change: That supplier does have enough capacity that we can access to fully meet our U S needs.

Speaker Change: And certainly yes.

Speaker Change: If tariffs are coming into play it would be very effective option for us to mitigate that exposure.

Roster.

Your first question comes from the line of Jason <unk> of Bank of America. Please go ahead.

Speaker Change: And there is no particular issues that I would note with regard to API and having that subject to tariff.

Renee Gala: Importantly, as we've said before, there is no change to the total doses of asparaginase with the new protocol that is in place, and so we expect we will be getting back to normalization in the second quarter and can continue to focus on the growth in AYA.

Hey, guys. Thanks for taking my question.

So I'm gonna respect Phils comment about not asking you to speculate on tariffs, but what I'm going to ask is about your supply chain and specifically <unk>. So you have a U S CMO and so I'm just curious if you can.

Speaker Change: Operator next caller please.

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

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

Jessica Fye: Hey, guys. Good afternoon. Thanks for taking my question. So following up on the first question, maybe thinking beyond <unk> can you talk about God, there's manufacturing footprint, including sources of API and.

Can speak to is not a very high volume product so.

Renée Galá: Hey, guys. Good afternoon. Thanks for taking my question. So, 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?

Jessica Fye: Hey, guys. Good afternoon. Thanks for taking my question. So, 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?

Phil Johnson: Maybe before we go to the next caller, I could just add something real quick. Annabel, if you think about our oncology performance, particularly year over year, here in the first quarter, I think it's important to keep in mind what I mentioned about there being one fewer shipping week effectively in the first quarter of this year. Obviously, it's hard to know, you 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 percent or roughly 8 percent of the opportunity.

Just curious to the extent that if need be and 2026, you could fully supply the product from your U S. CMO and if you can comment as your API can be sourced in the U S such that you've got a fully.

Jessica Fye: Any other possible mitigation strategies or contingency plans.

Jessica Fye: To neutralize any potential impact of Biopharma tariffs if they are implemented.

Supplied product for the U S market. Thanks.

Yes, Jason Thanks for the question and.

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

Date, you're being respectful of the prior comments is what we can comment on what we can.

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

So you are correct, we do have U S supplier for oxalate, including XI wave.

Speaker Change: Bruce and thanks for the question John.

That supplier does have enough capacity that we can access to fully meet our U S needs.

Operator: So certainly there was an impact on the year over year growth, just given the fact that we had one fewer shipping day. So keep that in mind if you think about the trends and what you're seeing.

Renée Galá: 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 US. 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 UK where we produce that product, and we have the capability to also develop other products at that plant. Some of our other smaller products on the oncology side are manufactured in different locations. Defitelio is in Villa Guardia, Italy. Vyxeos is manufactured by Sintra, 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 don't take lightly.

Renee Gala: 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 US. 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 UK where we produce that product, and we have the capability to also develop other products at that plant. Some of our other smaller products on the oncology side are manufactured in different locations. Defitelio is in Villa Guardia, Italy. Vyxeos is manufactured by Sintra, 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 don't take lightly.

Speaker Change: With respect to where we manufacturers <unk> Ziram 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 <unk>, we have a facility in the U K, where we produce.

And certainly if tariffs are coming into play it would be very effective option for us to mitigate that exposure.

Akash Tewari: Go to the next call, please.

Mike Riad: Your next question comes from Akash Tewari with Jeffrey. Please go ahead. Hey, this is Amy, I'm for Akash. Thanks so much for taking our question.

And there is no particular issues that I would note with regard to API and having that subject to tariff.

Speaker Change: Is that product and we have the.

Renee Gala: Just one for Horizon GEA, would love to get your expectations on the control arm performance and what gives you confidence that TRAC chemo isn't outperforming what was shown with chemo 811. Thanks so much. Rob. Yeah, so 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 JNKV trial, and then more recently, Keynote 811. And across those studies, the control arm of trastuzumab chemotherapy has performed pretty consistently with a medium PFS between, I think, about 6.9 months up to a high of about 8.1 months in the more modern era.

Speaker Change: The ability to to also develop other products at that plant and then some of our other smaller products on the oncology side.

Operator next caller please.

Your next question comes from Jessica Fye with J P. Morgan. Please go ahead.

Hey, guys. Good afternoon. Thanks for taking my question. So following up on the first question, maybe thinking beyond <unk> can you talk about this manufacturing footprint, including sources of API.

Speaker Change: Our manufactured in different locations and <unk> is in the Laguardia, Italy.

Speaker Change: <unk> is manufactured by Cintra, and then relates to manufactured in Denmark. So we do have quite a lot of manufacturing in Europe.

And any other.

Possible mitigation strategies or contingency plans.

To neutralize any potential impact of Biopharma tariffs if they are implemented.

Speaker Change: In terms of our capabilities.

And what options, we have going forward, obviously, making changes to our manufacturing.

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

Speaker Change: This is something that we don't take lightly and it does take a period of time that we do have a level of flexibility as we mentioned today with our Oxidate products and we'll continue to evaluate us backup options and other sources of manufacturing cell.

Renée Galá: It does take a period of time. But we do have a level of flexibility, as we mentioned today, with our oxybate products, and we'll continue to evaluate both backup options and other sources of manufacturing. Phil?

Renee Gala: It does take a period of time. But we do have a level of flexibility, as we mentioned today, with our oxybate products, and we'll continue to evaluate both backup options and other sources of manufacturing. Phil?

Hello, Bruce and thanks for the question, Jeff So with respect to where we manufacturers <unk> xyrem.

Rob Iannone: So through these three Phase III trials, I think it gives us a pretty good idea of what to expect from the control arm, and we planned accordingly. We continue to have confidence in standard data maps ability here. As you know, there have been two Phase IIs published. showing very promising results, Zanikemo with a median PFS of 15.2 months. That's the last publication in Zanikemo-Tizolizumab with a median PFS of 16.7 months. And at ASCO this year, we will update for the first time the overall survival data with Zanikemo. Prior to this, the median wasn't estimatable based on the maturity level.

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 <unk>, we have a facility in the UK, where we produce that product and we have the.

Speaker Change: Yes.

Ben: Great summary, and as you would expect Jeff This is Ben.

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

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

Ben: Subject of quite a bit of work across a cross functional team.

Ben: Since sort of late last year early this year and there certainly are opportunities for us to work with CMS.

The ability to to also develop other products at that plant and then some of our other smaller products on the oncology side.

<unk> here in the U S to further reduce the exposure to jazz beyond those that we're currently working with.

Our manufactured in different locations and <unk> is in the Laguardia, Italy Vic.

Ben: To date to the primary way that we buffered impact would be through <unk>.

<unk> is manufactured by Cintra, and then relates to manufactured in Denmark. So we do have quite a lot of manufacturing in Europe in terms of our capabilities.

Ben: 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 will continue with that strategy.

Rob Iannone: We look forward to presenting those data as well.

Ben: And then obviously, depending upon if and when tariffs come into effect, what geographies, they would impact and what rate.

Joseph Thome: Your next question comes from Joseph Thome with TD Cowen. Please go ahead. Good afternoon. Thank you for taking my question. On Dordavaprone, I think Chimerics paused enrollment in the Phase 3 study ahead of the acquisition. So kind of just curious if that has restarted and if you anticipate making any changes to the Phase 3 trial in the first-line patients? And 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 data, especially given Chimerics did do a little bit of a 180 on the submission?

And what options, we have going forward, obviously, making changes to our manufacturing.

Ben: We may have some protection from inventory for 2026 as well.

<unk> is something that we don't take lightly it does take a period of time, but we do have a level of flexibility as we mentioned today with our Oxidate products and we'll continue to evaluate us backup options and other sources of manufacturing cell.

Ben: Turn it back to the operator for the next question. Please.

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

David <unk>: Your next question comes from David <unk> with Piper Sandler. Please go ahead.

Operator: Your next question comes from David Amsellem with Piper Sandler. Please go ahead.

Ben: Okay.

David <unk>: So we wanted to ask a question about Scripps as Alka and competition from and Delta.

Bruce Cozadd: Actually, wanted to ask a question about Zepzelca and competition from Imdelltra. I know it's having an impact, and the label expansion is certainly not lost on me. But 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? And then also, how are you thinking about the expansion of Imdelltra itself, bearing in mind that Amgen has a pretty comprehensive development program in small cell lung in terms of earlier lines of therapy? So how are you thinking about Zepzelca overall as a growth product going forward? Thanks.

David Amsellem: Actually, wanted to ask a question about Zepzelca and competition from Imdelltra. I know it's having an impact, and the label expansion is certainly not lost on me. But 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? And then also, how are you thinking about the expansion of Imdelltra itself, bearing in mind that Amgen has a pretty comprehensive development program in small cell lung in terms of earlier lines of therapy? So how are you thinking about Zepzelca overall as a growth product going forward? Thanks.

Yes.

<unk> summary, and as you'd expect Jeff This is Ben.

Ben: It's having an impact.

The.

Subject of quite a bit of work across a cross functional team.

Joseph Thome: Thank you. Thank you for having me.

Ben: Label expansion is certainly not lost on me, but I guess my question here is.

Since sort of late last year early this year and there certainly are opportunities for us to work with CMS.

Rob Iannone: Yeah, happy to take those. So, with regard to the, 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 18th. The first part of your question was related to pausing enrollment and the ongoing confirmatory frontline trial. And just to clarify, that was paused only in the U.S. And, you know, 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, or to have a prone by prescription, which could confound the overall survival result.

Ben: How should we think about <unk> over time in terms of its trajectory do you anticipate.

<unk> here in the U S to further reduce the exposure to jazz beyond those that we're currently working with.

Ben: That.

Ben: <unk> contribution will overwhelm.

To date through the primary way that we buffered impact would be through <unk>.

Ben: The pressure in the second line setting and then also how are you thinking about the expansion of.

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 will continue with that strategy.

Ben: Ultra itself bearing in mind that Amgen has a pretty comprehensive development program in small cell lung.

Ben: In terms of earlier lines of therapy.

Ben: So how are you thinking about the Alco overall as a growth product going forward.

And then obviously, depending upon if and when tariffs come into effect, what geographies, they would impact and what rate.

We may have some protection for the inventory for 2026 as well.

Yes, I'm happy to jump in and take that one so as we think about <unk>. We did have some dynamics impacting the first quarter as we look forward, though to your point on <unk> returning to growth.

Renée Galá: Yeah, I'm happy to jump in and take that one. So as we think about Zepzelca, we did have some dynamics impacting Q1. 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 IMforte trial where we showed stat-sig and clinically meaningful PFS and OS in our study of first-line extensive-stage maintenance patients. And so 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.

Renee Gala: Yeah, I'm happy to jump in and take that one. So as we think about Zepzelca, we did have some dynamics impacting Q1. 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 IMforte trial where we showed stat-sig and clinically meaningful PFS and OS in our study of first-line extensive-stage maintenance patients. And so 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.

Okay.

Turn it back to the operator for the next question. Please.

Your next question comes from David <unk> with Piper Sandler. Please go ahead.

Yeah.

Ben: Even with competition and some delayed progression of first line limited stage patients coming into the second line that silica and the second line still remains the leading treatment as measured by market share importantly, we do look forward to both sharing our data at <unk>.

Rob Iannone: As you mentioned, while the trial isn't rolling very well, we would have time potentially to make changes to the analysis plan.

So we wanted to ask a question about Zap zilkha and competition from and ultra.

It is having an impact and the <unk>.

Rob Iannone: 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.

Label expansion is certainly not lost on me, but I guess my question here is how.

Ben: On the first line <unk> trial.

How should we think about <unk> over time in terms of its trajectory do you anticipate.

Ben: We showed that silicon politically meaningful PFS and OS in our study of first line extensive stage maintenance patients and so this is something we look forward.

That first line contribution will overwhelm the.

Gregory Renza: Your next question comes from Gregory Renza with RBC Capital Markets. Please go ahead. Hey, good evening, guys. Thanks. Thanks for taking my question.

The pressure in the second line setting and then also how are you thinking about the expansion of.

Presenting at <unk>, and then rapidly submitting that data for potential inclusion in MCC on treatment guidelines. We do expect this data to be practice changing and therefore going into the first line, we look to a larger patient population to treat in the.

Ultra itself bearing in mind that Amgen has a pretty comprehensive development program in small cell lung.

Renee Gala: My question is just on the Oxibates. And as Rene, 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 your reassurance about. Thanks for the question. So 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.

In terms of earlier lines of therapy.

So how are you thinking about the telco overall as a growth product going forward. Thanks.

Renée Galá: And 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. So we do expect this to contribute to future growth of the brand. And we would also expect patients that didn't receive Zepzelca in first line to have the opportunity to receive it in the second line. And then, Rob, do you want to take the question with respect to the views of tarlatamab going forward from a clinical perspective?

Renee Gala: And 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. So we do expect this to contribute to future growth of the brand. And we would also expect patients that didn't receive Zepzelca in first line to have the opportunity to receive it in the second line. And then, Rob, do you want to take the question with respect to the views of tarlatamab going forward from a clinical perspective?

Ben: Extensive stage patients, but also longer treatment duration. So we do expect this to contribute to future growth of the brand and we would also expect patients that didn't receive <unk> in first line to have the opportunity to receive that in the second line.

Yes, I'm happy to jump in and take that one so as we think about <unk>. We did have some dynamics impacting the first quarter as we look forward, though to your point on <unk> returning to growth.

West competition, and some delay progression of first line limited stage patients coming into the second line <unk> 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 <unk>.

Rob: And then Rob do you want to take the question with respect to <unk>.

Rob: The use of <unk> going forward from a clinical perspective.

Rob: Yes, again, I think you've covered it very well.

Renee Gala: 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. So 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. And we've had another, sorry, a number of other initiatives that are proving effective and really give us confidence in the growth.

Bruce Cozadd: 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, and it would be quite a while before a new trial would read out there. So 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. And then for patients who don't receive it in front-line, Zepzelca has data to show that it's an effective second-line therapy.

Rob Iannone: 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, and it would be quite a while before a new trial would read out there. So 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. And then for patients who don't receive it in front-line, Zepzelca has data to show that it's an effective second-line therapy.

On the first line <unk> trial.

Rob: <unk>.

Rob: With our new data and ultimately adoption into NCC and in the label as first line.

We showed stats silicon clinically meaningful PFS and OS and our study of first line extensive stage maintenance patients and so this is something we look forward to it.

Rob: Is that that affords us a larger population for a longer duration of therapy through either maps not approved in that.

Resenting ASKO and then rapidly submitting that data for potential inclusion in MCC on treatment guidelines. We do expect this data to be practice changing and therefore going into the first line, we look to a larger patient population to treat in the.

Rob: Savi.

Rob: And it would be quite a while for a new trial would read out there.

Rob: That's the.

Rob: 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 some outcome.

Extensive stage patients, but also longer treatment duration. So we do expect us to contribute to future growth of the brand and we would also expect patients that didn't receive <unk> in first line to have the opportunity to receive that in the second line.

Rob: And then for patients who don't receive a new frontline's it's okay.

Rob: It has data to show that it's an effective second line therapy.

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

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

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

And then Rob do you want to take that.

Marc Goodman: Bill your comments about tariffs not impacting 2025 I assume has to do with the fact that you have inventory.

Question with respect to <unk>.

Jessica Fye: 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 US and so you don't have to worry about it. But 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?

Marc Goodman: 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 US and so you don't have to worry about it. But 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?

The use of <unk> going forward from a clinical perspective.

Marc Goodman: Just philosophically in the U S will still have to worry about it but is it fair question to ask what would be the impact.

Yes, again, I think you've covered it very well.

Marc Goodman: For a full year just on an annual basis. If you didn't have all that inventory built up like what would we be talking about here as far as the numbers.

<unk>.

With our new data and ultimately adoption into NCC and in the label as first line.

Mark: Yes, Mark I appreciate the question.

Bruce Cozadd: Yeah, Mark, 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. So we're 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're getting effectively this year. And then we also have the ability for our OxyBate products to use US 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 US to further reduce the impact. But I feel very good about the position that we're in currently, obviously, closely monitoring the situation, and we'll take actions as needed.

Phil Johnson: Yeah, Mark, 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. So we're 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're getting effectively this year. And then we also have the ability for our OxyBate products to use US 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 US to further reduce the impact. But I feel very good about the position that we're in currently, obviously, closely monitoring the situation, and we'll take actions as needed.

Mark: Sort of in this theoretical realm of what might happen in the future.

Is that that affords us the larger population for a longer duration of therapy through added maps not approved in that.

Mark: It depends obviously on what kind of rates being put in and what kind of geography are affected so we're not commenting at this point in time on those hypothetical.

Joel Beatty: Your next question comes from Joel Beatty with Baird. Please go ahead. All right, thanks for taking the question.

Setting.

And it would be quite a while before a new trial would read out there so I think thats.

Mark: I would say again, depending on when the tariffs would go into effect. If they are we could get some coverage from inventory as we're getting effectively this year and then we also have the ability for our <unk> products to use U S sourced effectively mitigate that exposure.

As a new standard of care I think that's the key the extensive stage patients who don't progress after induction.

Rob Iannone: And Dr. Bravone, can you discuss a little bit more about where it could fit in the treatment algorithm initially upon approval? And then also, when could the first results come from the action trial that might affect how it's used? Rob? Yes, so 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 frontline setting after patients receive the bulking surgery and radiation therapy, and that will give us an opportunity to expand to the frontline. We haven't given specific dates on when that would read out, but we have said it's enrolling to...

As you said should become the standard of care to get some outcome.

And then for patients who don't receive a new frontline's it's okay.

<unk> has data to show that it's an effective second line therapy.

Mark: Beyond that the main.

Mark: <unk> 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 but feel very good about the position that we're in currently obviously closely monitoring the situation and we will take actions as needed.

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

Bill your comments about tariffs not impacting 2025 I assume has to do with the fact that you have inventory that you've just philosophically in the U S. And so you have to worry about it but is it fair question to ask what would be the impact for a full year just on an annual basis.

Speaker Change: Your next question comes from Andrea Newkirk of Goldman Sachs. Please go ahead.

Operator: Your next question comes from Andrea Newkirk of Goldman Sachs. Please go ahead.

Hi, all this is Tony on for Andrea Thanks for taking my questions today.

If you didn't have all that inventory built up like what would we be talking about here as far as the numbers.

David Amsellem: Hi, all. This is Talania on for Andrea. Thanks for taking our questions today. Would you want to understand a little bit better why the Kymerix acquisition makes 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.

[Analyst] (Goldman Sachs): Hi, all. This is Talania on for Andrea. Thanks for taking our questions today. Would you want to understand a little bit better why the Kymerix acquisition makes 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.

Speaker Change: Would you.

Speaker Change: Wanted to understand a little bit better why does the <unk> acquisition makes sense for that and what do you find most compelling about the Dod have upon commercial opportunity and related to that how are you thinking about additional BD activity is going forward. Thank you.

Yes, Mark I appreciate the question.

Ami Fadia: Your next question comes from Ami Fadia with Needham. Please go ahead. Thanks for taking my 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 geography are affected so we're not commenting at this point in time on those hypotheticals.

Speaker Change: Okay.

Rob Iannone: Can you provide us with an update on JCP441, where you are with the NT1 study and when we might get an update on that? And then 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? And 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 in organically. Thank you.

Speaker Change: So maybe I'll jump in at the total company acquisition level and then.

[Analyst]: So maybe I'll jump in at the total company acquisition level. And 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. And 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.

Bruce Cozadd: So maybe I'll jump in at the total company acquisition level. And 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. And 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.

Rob: Rene Rob if you want to add anything on <unk>, and particularly you can.

I would say again, depending on when tariffs would go into effect. If they are we could get some coverage from inventory as we're getting effectively this year and then we also have the ability for our <unk> products to use U S sourced effectively mitigate that exposure.

Speaker Change: We've been I think pretty clear about our corporate development strategy for some time now.

Speaker Change: 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.

Beyond that the main two.

Speaker Change: Portfolio and in our R&D efforts.

<unk> 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 but feel very good about the position that we're in currently obviously closely monitoring the situation and we will take actions as needed.

Speaker Change: We've been clear that our priorities include finding products that would represent.

Speaker Change: A real advance where there is unmet medical need.

Phil Johnson: I'm just going to remind people, try to limit it to one question. But on this one, maybe, Rob, you could talk about 441. And then, Phil, if you want to jump in on corporate development priorities. 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, you know, when we would share information on those data just this year. Yeah, I'm sorry, the second part of the question.

Speaker Change: In a serious condition that aligns with our capabilities that has an efficient commercial call point, so that we don't need to do.

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

Speaker Change: Massive buildup both commercial.

Hi, all this is Tony on for Andrea Thanks for taking my questions today.

Speaker Change: Expense that have long durability.

Would you.

Speaker Change: And we really feel that time Eric's on all fronts was a perfect fit for us matches, well with what we do well, particularly in oncology near term launch.

I want to understand a little bit better why does the <unk> acquisition makes sense for that and what do you find most compelling about the road have upon commercial opportunity and related to that how are you thinking about additional BD activities going forward. Thank you.

[Analyst]: And we really feel that Kymerix 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?

Bruce Cozadd: And we really feel that Kymerix 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?

Speaker Change: Again efficient and.

So maybe I'll jump in.

The total company acquisition level and then.

Speaker Change: And we're confident fills.

Phil Johnson: So 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, create value for shareholders. We finished the first quarter in a really strong financial position with $2.6 billion in cash investments, $430 million in operating cash flow in the quarter. So even after the payment of roughly $890 million net to acquire Chimerics, 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.

Speaker Change: Serious unmet need.

Rene Rob if you want to add anything on <unk> in particular you can.

Speaker Change: Rob you want to jump in.

We've been I think pretty clear about our corporate development strategy for some time now.

Speaker Change: Yes, I'd love to.

Speaker Change: The treatment for diffuse we own.

Bruce Cozadd: Yeah, I'd love to. The treatment for diffuse glioma hasn't changed since I trained as a pediatric oncologist 25 years ago. Patients get debulking surgery, which is never curative, and then radiation therapy. And that's essentially it. Prior to dordaviprone and prior to the discovery that H3K27M mutations occurred and were a driver for oncogenesis in this setting, it's 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 they indicated, that has an ongoing very high unmet need and without many other prospects, unfortunately.

Rob Iannone: Yeah, I'd love to. The treatment for diffuse glioma hasn't changed since I trained as a pediatric oncologist 25 years ago. Patients get debulking surgery, which is never curative, and then radiation therapy. And that's essentially it. Prior to dordaviprone and prior to the discovery that H3K27M mutations occurred and were a driver for oncogenesis in this setting, it's 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 they indicated, that has an ongoing very high unmet need and without many other prospects, unfortunately.

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.

Speaker Change: We changed the titrated as a pediatric oncologist 25 years ago patient, Kent, Bulking surgery, which is never curative and then radiation therapy.

Portfolio and in our R&D efforts and we've been clear that our priorities include finding products that would represent.

Speaker Change: And that's essentially it prior to <unk> and prior to the discovery that.

Speaker Change: Page three K 27, 10 mutations occurred and where a driver.

A real advance where there is 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.

Speaker Change: For oncogenesis in this setting.

Speaker Change: As shown now with their data prune that for patients with this mutation.

The therapy is effective we're really impressed with.

Massive buildup both commercial.

Not only the efficacy, but also the safety profile.

Phil Johnson: We do look at both licensing, like we did very successfully with the licensing deal with Zymwerx that's brought us, obviously, Zahira. And then, obviously, for acquisitions like we've done, we've been very successful looking forward to the upcoming PDUFA and then hopefully launch right thereafter of Dordavoprun. So 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. And 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.

Expense that have long durability.

Speaker Change: <unk> setting.

Speaker Change: Indicated.

And we really feel that <unk> on all fronts was a perfect fit for us matches, well with what we do well, particularly in oncology near term launch.

Speaker Change: Ongoing very high unmet need and without many other.

Speaker Change: Prospects virtually.

Annabel <unk>: Your next question comes from Annabel <unk> of Stifel. Please go ahead.

Again efficient and.

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

And we're confident fills.

A serious unmet need.

Annabel <unk>: Hi, Thanks for taking my question so for O'reilly as I understand obviously that the protocols have changed for the pediatric indication that's always treatment.

Renée Galá: Hi. Thanks for taking my question. So for Rylaze, I understand, obviously, that the protocols have changed for the pediatric indication that delays treatment. But 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. And when do you think we can get some critical mass there and some momentum to return Rylaze back to growth?

Annabel Samimy: Hi. Thanks for taking my question. So for Rylaze, I understand, obviously, that the protocols have changed for the pediatric indication that delays treatment. But 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. And when do you think we can get some critical mass there and some momentum to return Rylaze back to growth?

Rob you want to jump in.

Yes, I'd love to.

The the treatment for disease, we own.

Annabel <unk>: But what can we what can we expect for pick up in a while it's been I guess quite a little bit of time that you've been trying to drive.

It Hasnt changed since I trained as a pediatric oncologist 25 years ago patients get bulking surgery.

Phil Johnson: But probably 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. So I hope that gives you some context.

Just never curative and then radiation therapy.

Annabel <unk>: Growth in that area and when do you think we can get some critical mass there is some momentum to return relates back to work.

And that's essentially it prior to <unk> and prior to the discovery that <unk>.

Renee.

<unk> three K 27 10.

Renee: Yes. Thanks, I had a question there with respect to the <unk> segment. It really does take time to drive education with adult treaters to use asparaginase and <unk>. These are.

[Analyst]: Renee?

Bruce Cozadd: Renee?

Mutations occurred and were a driver.

Renée Galá: 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. And so 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. And it's also resulted in much higher overall survival, which is good news for patients. So we are having some momentum and success with respect to the AYA segment.

Renee Gala: 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. And so 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. And it's also resulted in much higher overall survival, which is good news for patients. So we are having some momentum and success with respect to the AYA segment.

For oncogenesis in this setting.

It's been shown now with their diamond prune that for patients with this mutation.

Operator: If we can go to the next caller, please.

Ashwani Burma: Your next question comes from Ashwani Burma of UBS, excuse me, please go ahead. Hi, yeah, thanks for taking my question. I just wanted to clarify, like, so when you, 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? Yes, that would have been across our US oncology business and common for the various products there.

The therapy is effective we're really impressed with.

Renee: Treaters that often have a different protocol that theyre following and so we were certainly pleased last year with the updated results from the protocol that created the gap and spirit <unk> treatment because although it created.

Not only the efficacy, but also the safety profile.

The disease setting as I indicated.

Ongoing very high unmet need.

And without many other.

Prospects Fortunately.

A delay in when Asparaginase is dosed and it has led to some of the challenges that we've had with revenues.

Your next question comes from Annabel <unk> of Stifel. Please go ahead.

Hi, Thanks for taking my question.

Renee: We feel very confident that it is.

Renee Gala: Renee, if you want to add? No, that's correct.

So for Riley as I understand.

Renee: Demonstrating the importance of asparaginase.

Say that the protocols have changed for the pediatric indication that delays treatment.

Renee: Treatment and it's also resulted in much higher overall survival, which is good news for patients.

Renee Gala: Your next question comes from Mohit Bansal with Wells Fargo. Please go ahead. Great. Thank you for taking my question. I have a question for you, Rob. So in our conversation with some breast cancer doctors, the interesting takeaway was that it is not a hormone confusion that an HER2 would become a first-line agent for all the HER2-positive patients. Likely part of it is safety and comfort with the Cleopatra regimen.

But what quick what point do you expect for pick up in a way its been I guess quite a little bit of time that you've been trying to drive.

Renee: Having.

Renee: Momentum and success with respect to the AIA segment. It does take a little bit more time than what we see in pediatrics, where we've had pretty much universal adoption, but there has been some delay in getting back to that continued use importantly is.

Growth in that area and when do you think we should get some critical mass there and some momentum to return relates back to Earth.

Renée Galá: It does take a little bit more time than what we see in pediatrics where we've had pretty much universal adoption. But 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. And so we expect we will be getting back to normalization in Q2 and can continue to focus on the growth in AYA.

Renee Gala: It does take a little bit more time than what we see in pediatrics where we've had pretty much universal adoption. But 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. And so we expect we will be getting back to normalization in Q2 and can continue to focus on the growth in AYA.

Renee.

Yes. Thanks for the question there with respect to the AIA segment. It really does take time to drive education with adult treaters to use asparaginase and <unk>. These are.

We've said before there is no change to the total doses of asparaginase that the new protocol that is in place and so we expect we will be getting back to normalization in the second quarter and can continue to focus on the growth in AIA.

Renee Gala: So the question is, do you see a potential for Zany to be the first line as well? And what kind of trials you may have to do then because chiropractor is a really long regimen here. Thank you. Sure, well, I mean, I would just reinforce our primary strategy, which is to position AFTER and HER2 because of the data we've generated showing activity of Xana, you know, very promising activity after just about any prior and even multiple different HER2 agents, you know, including standard frontline therapy, which is Receptin, Progena, and Chemo, and HER2 TDM1 to Cadmium, et cetera.

Treaters that often have a different protocol that theyre following and so we were certainly pleased last year with the updated results from the protocol that created the gap and spirit <unk> treatment because although it created.

Renee: Maybe before I go to the next caller I can just add something real quick.

Bruce Cozadd: Maybe before we go to the next caller, I could just add something real quick. Annabel, if you think about our oncology performance, particularly year-over-year, here in the first quarter, I think it's important to keep in mind what I've mentioned about there being one fewer shipping week effectively in the first 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 1 out of 13 is 7.7% or roughly 8% of the opportunity. So certainly, there was an impact on the year-over-year growth just given the fact that we had one fewer shipping day. So keep that in mind as you think about the trends and what you're seeing. Go to the next caller, please.

Phil Johnson: Maybe before we go to the next caller, I could just add something real quick. Annabel, if you think about our oncology performance, particularly year-over-year, here in the first quarter, I think it's important to keep in mind what I've mentioned about there being one fewer shipping week effectively in the first 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 1 out of 13 is 7.7% or roughly 8% of the opportunity. So certainly, there was an impact on the year-over-year growth just given the fact that we had one fewer shipping day. So keep that in mind as you think about the trends and what you're seeing. Go to the next caller, please.

Renee: And if you think about our oncology performance, particularly year over year here in the first quarter I think it's important to keep in mind, what I've mentioned about there being one fewer shipping week effectively in the first quarter of this year.

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 treatment and it's also resulted in much higher overall survival, which is good news for patients.

Speaker Change: It's hard to know.

Speaker Change: When you have an additional week youre getting that average rate higher or lower but just on pure math missing one out of 13% to seven 7% of roughly 8% of the opportunity. So certainly there was an impact on the year over year growth just given the fact that we had one fewer shipping day.

Renee Gala: So positioning it AFTER and HER2, which is currently second line and likely to move to frontline for, I would say, a great majority of patients in this disease setting is really very meaningful. And there won't 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 treatment. of Therapy. You're right that there would be a few, there would be some patients who may not tolerate and hurt to or would have some pre-existing condition that would prevent them from, and I think in those cases, patient who's either progressed on or intolerant in HER2 could move on to ZanaDataMap based on the 303 trial.

We are having.

Momentum and success with respect to the AIA segment. It does take a little bit more time that than what we see in pediatrics, where we've had pretty much universal adoption, but there has been some delay in getting back to that.

So keep that in mind, if you think about the trends and what Youre seeing.

Speaker Change: Go to the next caller please.

Speaker Change: Your next question comes from our cash Tomorrow with Jefferies. Please go ahead.

Continued use importantly, as we've said before there is no change to the total doses of asparaginase that the new protocol that is in place and so we expect we will be getting back to normalization in the second quarter and can continue to focus on to grow.

Operator: Your next question comes from Akash Tawari with Jefferies. Please go ahead.

Speaker Change: Hey, this is Amy answer costing so much for taking our question just one for horizon Gea would love to get your expectations on the control arm performance and what gives you confidence that tret chemo isn't outperforming what was shown at <unk>.

David Amsellem: Hey, this is Amy on for Kosh. 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 chemo isn't outperforming what was shown with KEYNOTE-811. Thanks so much.

[Analyst] (Jefferies): Hey, this is Amy on for Kosh. 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 chemo isn't outperforming what was shown with KEYNOTE-811. Thanks so much.

Speaker Change: Thanks, so much.

<unk> and <unk>.

Renee Gala: You know, if in HER2, you know, is ultimately approved in the frontline setting, I do think it will be the great majority of patients who get it, you know, based on the strong efficacy.

Speaker Change: Rob.

Maybe before I go to the next caller I can just add something real quick.

Speaker Change: Yes, so as you know theres been quite a bit of experience in this first line her two positive setting.

[Analyst]: Rob?

Bruce Cozadd: Rob?

Bruce Cozadd: Yeah. So 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. And 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. So through these three phase 3 trials, I think it gives us a pretty good idea of what to expect from the control arm, and we plan accordingly. We continue to have confidence in zanidatamab's ability here. As you know, there have been two phase 2s published showing very promising results. Zanidatamab chemo with a median PFS of 15.2 months. That's the last publication.

Rob Iannone: Yeah. So 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. And 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. So through these three phase 3 trials, I think it gives us a pretty good idea of what to expect from the control arm, and we plan accordingly. We continue to have confidence in zanidatamab's ability here. As you know, there have been two phase 2s published showing very promising results. Zanidatamab chemo with a median PFS of 15.2 months. That's the last publication.

And if you think about our oncology performance, particularly year over year here in the first quarter.

Speaker Change: From the original toga trial that was the basis for the approval of Herceptin through the Jacob trial, and then more recently keynote 811.

Keep in mind, what I've mentioned about there being one fewer shipping week effectively in the first quarter of this year, probably hard to know.

Sean Lalman: Your next question comes from Sean Lalman of Morgan Stanley, please go ahead.

And across those studies the control arm of Trastuzumab and chemotherapy has performed pretty consistently.

When you have an additional week youre getting that at an average rate higher or lower but just on pure math missing one out of 13% to seven 7% of roughly 8% of the opportunity. So certainly there was an impact on the year over year growth just given the fact that we had one fewer shipping day.

Mike Riad: Hi, this is Mike Riad on for Sean Laman. Thank you for taking our question. For XyWave and narcolepsy, are you able to provide a more granular breakout for patients who need to oxidate versus high sodium switches? And then in IH, how are you thinking about XyWave value proposition with potential for a competitive threat there from the rise? Thank you.

Speaker Change: The median PFS between I think about six nine months up too high of about $8 one month in the more.

Speaker Change: Modern era so.

Speaker Change: Through these three phase III trials and I think it gives us a pretty good idea of what to expect from the control arm.

So keep that in mind as you think about the trends and what you are seeing.

Go to the next caller please.

Renee Gala: Renee? Yeah, so with respect to the narcolepsy ads, we have seen primarily ads in the quarter coming from new to oxidate patients. And 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, and 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 Zywave offers.

Speaker Change: We plan accordingly.

Your next question comes from our cash to worry with Jefferies. Please go ahead.

Speaker Change: We continue to have confidence in <unk> ability here as you know there have been two phase III.

Hey, this is Amy unfair cost. Thanks, so much for taking our question, Jeff one for Horizon Gea would love to get your expectations on the control arm performance and what gives you confidence that tret chemo isn't outperforming what was shown at <unk>.

Speaker Change: <unk>.

Speaker Change: Showing very promising results.

Speaker Change: Danny Chemo with a median PFS of 15 two months, that's the last publication and savvy Cumulus is Elisa ma'am.

Speaker Change: Median PFS of $16 seven months and at <unk>. This year, we will update for the first time.

Bruce Cozadd: And Zepzelca chemo atezolizumab with a median PFS of 16.7 months. And at ASCO this year, we will update for the first time the overall survival data with Zepzelca chemo. Prior to this, the median wasn't estimatable based on the maturity level. So we look forward to presenting those data as well.

Rob Iannone: And Zepzelca chemo atezolizumab with a median PFS of 16.7 months. And at ASCO this year, we will update for the first time the overall survival data with Zepzelca chemo. Prior to this, the median wasn't estimatable based on the maturity level. So we look forward to presenting those data as well.

Evan Thanks, so much.

Rob.

Yes, so as you know theres been quite a bit of experience in this first line.

Speaker Change: Overall survival data with Fannie chemo prior to this.

<unk> positive gea setting.

From the original toga trial that was the basis for the approval of Herceptin through the Jacobs trial, and then more recently keynote 811.

Speaker Change: Medium wasn't estimated based on the maturity level.

Speaker Change: Look forward to presenting those data as well.

And across those studies the control arm of Trastuzumab and chemotherapy has performed pretty consistently.

Speaker Change: Your next question comes from Joseph <unk> with TD Cowen. Please go ahead.

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

Speaker Change: Good afternoon. Thank you for taking my question.

Renee Gala: So 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, Zywave is the only low sodium option. And 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. And so we do continue to see all high sodium oxidate patients as potential Zywave patients. And keep in mind that within our label for Zywave for idiopathic hypersomnia, there is flexible dosing.

With a median PFS between I think about six nine months up too high of about $8 one months in the more.

[Analyst]: Hi there. Good afternoon. Thank you for taking my question. On dordaviprone, I think Kymerix paused enrollment in the phase three study ahead of the acquisition. So kind of just curious if that has restarted and if you anticipate making any changes to the phase three trial in the first-line patients. And 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 Kymerix did do a little bit of a 180 on the submission? Thank you. Rob?

Joseph Thome: Hi there. Good afternoon. Thank you for taking my question. On dordaviprone, I think Kymerix paused enrollment in the phase three study ahead of the acquisition. So kind of just curious if that has restarted and if you anticipate making any changes to the phase three trial in the first-line patients. And 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 Kymerix did do a little bit of a 180 on the submission? Thank you.

Speaker Change: On <unk> I think <unk> pause enrollment in the phase III study ahead of the acquisition. So 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.

Modern era so.

Through these three phase III trials I think it gives us a pretty good idea of what to expect from the control arm.

We plan accordingly.

Speaker Change: Is on track with the upcoming could do for data, especially given <unk> to do a little bit of a 180 on the submission. Thank you.

We continue to have confidence in <unk> ability here as you know there have been two phase Iis.

<unk>.

Bruce Cozadd: Rob?

Speaker Change: Rob.

Showing very promising results.

Yes happy to take those.

Danny Chemo with a median PFS of 15 two months at the last publication and Sami Cumulus is Elisa Mab with EMEA median PFS of $16 seven months and in <unk>.

Bruce Cozadd: Yeah, happy to take those. So 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 target action date of 18 August. The first part of your question was related to pausing enrollment in the ongoing confirmatory front-line trial. And just to clarify, that was paused only in the US. And 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 isn't enrolling very well, we would have time potentially to make changes to the analysis plan.

Rob Iannone: Yeah, happy to take those. So 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 target action date of 18 August. The first part of your question was related to pausing enrollment in the ongoing confirmatory front-line trial. And just to clarify, that was paused only in the US. And 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 isn't enrolling very well, we would have time potentially to make changes to the analysis plan.

Speaker Change: So.

Speaker Change: With regard to the.

Speaker Change: With regards to the FDA.

Speaker Change: So far the review is going exactly as we'd expect.

Speaker Change: No surprises there and no indication.

This year, we will update for the first time.

Speaker Change: We would be off of our Paducah date of.

The overall survival data with Fannie chemo prior to this.

Speaker Change: August.

The medium wasn't estimated based on the maturity level.

Speaker Change: 18th.

Renee Gala: That indication is twice nightly or once nightly, depending on what the physician and the patient choose to pursue in terms of their therapy. So we feel we're quite well positioned with respect to narcolepsy and idiopathic hypersomnia.

Speaker Change: The first part of your question was related to pausing enrollment in the ongoing confirmatory frontline trial just to clarify that was posed.

We look forward to presenting those data as well.

Your next question comes from Joseph <unk> with TD Cowen. Please go ahead.

In the U S and there we are anticipating an approval availability of drug and therefore.

Good afternoon, and thank you for taking my question.

<unk> I think <unk> pause enrollment in the phase III study ahead of the acquisition. So 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.

We want to avoid the problem of patients enrolling in then.

Phil Johnson: I will also just jump in and point out that You know, for those of you that saw the court decision today, you know, given that our IP has been found to be valid, that Avidel has admitted to infringing it, we still don't see even after today's ruling a viable path for Avidel to commercialize, plumerize NIH before the expiration of the relevant patent in 2036. So I totally agree with everything Renee said in terms of, you know, potential competitive positioning and differences between the product. But it's there's, you know, there's some some room to go before we actually do have competition in NIH.

Speaker Change: Crossing over from the control arm to get.

Speaker Change: Or to have a promo prescription which could confound the overall survival results.

Speaker Change: As you mentioned, while the trial is it growing.

Speaker Change: Well.

Speaker Change: Would have time potentially to make changes to the analysis plan.

<unk> is on track with the upcoming <unk>, especially given <unk> to do a little bit of a 180 on the submission. Thank you.

Speaker Change: We haven't announced any of those changes, but certainly we will look at that carefully to be sure that that trial as well.

Bruce Cozadd: 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.

Rob Iannone: 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.

Rob.

Speaker Change: Well powered to deliver.

Yes happy to take those.

Speaker Change: The results not only in a timely fashion, but that would be most informative.

So.

With regard to the.

With regards to the FDA.

So far the review is going exactly as we'd expect.

Speaker Change: Your next question comes from Gregory <unk> with RBC capital markets. Please go ahead.

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

No surprises there and no indication that.

We would be off of our Paducah date of.

Gregory: Hey, good evening guys. Thanks, Thanks for taking my question.

Jessica Fye: Hey, good evening, guys. Thanks for taking my question. My question is just on the oxybate. And 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.

Gregory Renza: Hey, good evening, guys. Thanks for taking my question. My question is just on the oxybate. And 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.

August.

Gary Nachman: Your next question comes from Gary Nachman with Raymond James. Please go ahead. Thanks, and good afternoon.

Speaker Change: My question is just on the OXXO Bates and as Renee.

18th.

The first part of your question was related to pausing enrollment in the ongoing confirmatory frontline trial and just to clarify that was posed.

Gregory: We're articulating just some effectiveness on the campaigns.

Renee Gala: So first I hear on BTC, understanding it's a small indication, how is the ramp going? How rapid is the penetration? And what's the anecdotal feedback on how the drug is performing? And have there been any challenges with access and how you're helping facilitate that?

Gregory: And how those are performing well I just wanted to give you an opportunity to elaborate a little bit about what youre seeing and what the direct impacts are from.

In the U S and there we are anticipating an approval in availability of drug and therefore.

Gregory: The campaigns that have led to your reassurance about contribution in the growth of the IH market. Thanks, so much.

We want to avoid the problem of patients enrolling in then.

Crossing over from the control arm.

Gregory: Yes. Thanks for the question. So 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 interaction.

Renee Gala: And then, if GEA ends up being positive in first line as a bigger market, would you consider changes to pricing at all? And also how your promotional efforts would change for that indication versus BTC? Thanks. Yeah, thanks for the question. So we had our first patients treated in December, shortly after launch for BTC, and the reception has been quite positive. HCPs are glad to have Zyhera available to treat patients. Just as a reminder, BTC is a very small patient population, 3000 patients in the US in first line and second line. And therefore, we do expect revenues from this first indication, as we've stated, to be quite modest.

<unk>.

Through data promos prescription, which could confound the overall survival results.

Renée Galá: Yeah. Thanks for the question. So we are seeing beneficial response to the campaigns. 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. So 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. And we've had a number of other initiatives that are proving effective and really give us confidence in the growth.

Renee Gala: Yeah. Thanks for the question. So we are seeing beneficial response to the campaigns. 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. So 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. And we've had a number of other initiatives that are proving effective and really give us confidence in the growth.

As you mentioned, while the trials are growing very well.

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 as well.

Gregory: 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 theres not a lot of incentive to.

Well powered to deliver.

The results not only in a timely fashion, but that would be most informative.

Your next question comes from Gregory <unk> with RBC capital markets. Please go ahead.

Gregory: Actually diagnose someone with idiopathic hypersomnia, so not only have we had good success with the digital and media campaigns that I mentioned that we've continued to sharpen our execution in the field, we have continued to grow new prescribers.

Hey, good evening guys. Thanks, Thanks for taking my question.

My question is just on the OXXO Bates and as Renee.

Ne.

Renee Gala: In terms of access, we haven't really had any issues. What we're in, 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. And certainly, the the efficacy supporting this approval is something that they're excited to be able to bring to patients.

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 youre seeing and what the direct impacts are from the campaigns that have led to your reassurance about contribution in the growth of the IH markets. Thanks, So much.

Gregory: We've had great success with our field nurse educator program and we've had another sorry, 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 first quarter of 2025 and compare that to where we were.

Yes. Thanks for the question. So 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 interaction.

Renée Galá: If you look at where we ended this quarter, Q1 2025, and compare that to where we were a year ago stepping out of Q1 2024, looking at the patient adds, we've seen an increase of 5%. And that is in a mature market with competition, which is really great progress. Then with idiopathic hypersomnia, we've had an increase of 39% looking at the progress over the last 12 months. So we're really excited about the continued momentum that we have. Certainly, we have seasonality each year in the first quarter, but still executing really well in this area.

Renee Gala: If you look at where we ended this quarter, Q1 2025, and compare that to where we were a year ago stepping out of Q1 2024, looking at the patient adds, we've seen an increase of 5%. And that is in a mature market with competition, which is really great progress. Then with idiopathic hypersomnia, we've had an increase of 39% looking at the progress over the last 12 months. So we're really excited about the continued momentum that we have. Certainly, we have seasonality each year in the first quarter, but still executing really well in this area.

Gregory: Year ago.

Gregory: Being out of the first quarter of 2024 looking at the patient adds we've seen an increase of 5% and that is in a mature market with competition, which is really great progress then with idiopathic hypersomnia, we've had an increase of 39% looking.

Renee Gala: 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 Zipfelka. Of course, we would not promote without having an approval, but having the product on NCC and 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 slash approval.

<unk> 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 theres not a lot of incentive.

Gregory: At the progress over the last 12 months. So we're really excited about the continued momentum that we have certainly we have seasonality each year in the first quarter, but still executing really well in this area.

But to actually diagnose someone with idiopathic hypersomnia.

So not only have we had good success with the digital and media campaigns that I mentioned that 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 and we've had it.

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

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

Gregory: Yeah.

Gregory: Hi, Thanks for taking the question.

Gregory: <unk>.

[Analyst]: Hi. Thanks for taking the question. And dordaviprone, could you discuss a little bit more about where it could fit in the treatment algorithm initially upon approval, and then also when could the first results come from the ACTION trial that might affect how it's used? Rob?

Joel Beatty: Hi. Thanks for taking the question. And dordaviprone, could you discuss a little bit more about where it could fit in the treatment algorithm initially upon approval, and then also when could the first results come from the ACTION trial that might affect how it's used?

Gregory: Got a little bit more about where it could fit in the treatment algorithm. Initially upon approval and then also one could.

Renee Gala: So stay tuned. But we think given the benefit that we are seeing in efficacy, we'll be in a good position to do that. position where we are today.

Another sorry, 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 first quarter of 2025 and compare that to where we were a year ago stepping out of the first quarter of 2024 looks.

Gregory: First results come from the action trial.

Gregory: Psychologist.

Bruce Cozadd: Rob?

Gregory: Rob.

Gregory: Yes, so we expect.

Charles Duncan: Your next question comes from Charles Duncan with Cantor Fitzgerald.

Gregory: Based on the submission that we.

Bruce Cozadd: Yeah. So 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. And that will 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.

Rob Iannone: Yeah. So 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. And that will 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.

Gregory: We've made we expect the initial accelerated approval to be in the recurrent setting.

Renee Gala: Please go ahead. On for Charles. Thank you for taking our questions. So you reiterated confidence in Epidiolex reaching blockbuster status in 2025. Can you speak about any catalysts or what market dynamics underpinned that expectation? And also, can you talk about any meaningful... of the U.S. or in off-label usage that could contribute to this trajectory. Thank you. Yeah, Renee. Yeah, I didn't hear the full question.

At the patient adds we've seen an increase of 5% and that is in a mature market with competition, which is really great progress then with idiopathic hypersomnia, we've had an increase of 39% looking at the progress over the last 12 months. So we're.

Gregory: Action trials you know.

Gregory: Is treating in the frontline setting after patients receive to bulking surgery, and radiation therapy, and that will give us an opportunity to expand to the frontline we havent given specific dates on when that would read out, but we have said it.

Gregory: Enrolling.

Going to plan.

Really excited about the continued momentum that we have certainly we have seasonality each year in the first quarter, but still executing really well in this area.

Speaker Change: Your next question comes from Amy <unk> with Needham. Please go ahead.

Operator: Your next question comes from Amy Fadia with Needham. Please go ahead.

Amy: Hi, Thanks for taking my question can you provide us with an update on GBP 41, where you are with <unk>.

Bruce Cozadd: But what I understood was one Yeah, I can jump I can jump in on I can jump in on the first part, Renee, and just say, you know, our confidence that remains on track for blockbuster status is in part driven by It's already, you know, 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. Rene, you can comment on where where growth can be coming from, but, you know, we're very solidly on track. Yeah, thanks, Bruce.

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

David Amsellem: Hi, Kristen. Thanks for taking my question. Can you provide us with an update on JZP441, where you are with the NT1 study, and when we might get an update on that? And then 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? And 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.

Ami Fadia: Hi, Kristen. Thanks for taking my question. Can you provide us with an update on JZP441, where you are with the NT1 study, and when we might get an update on that? And then 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? And 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.

Amy: One study and then they might and an update on that and then just more broadly touching upon the comments previously around business development.

Hi, Thanks for taking the question.

They're not <unk>.

Scott a little bit more about where it could fit in the treatment algorithm. Initially upon approval and then also one could.

Amy: Have your priorities changed evolved.

First results come from the action trials my psychologist.

Amy: In the last couple of months as we've seen the market change and if you could sort of comment on.

Rob.

Amy: What types of assets, whether it's by the therapeutic area or the state of Nevada, and then you'd be focused on as you think about adding something inorganically. Thank you.

Yes, so we expect.

Based on the submission that we.

Renee Gala: The call had cut out for me. So we are quite, 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. And that data continues to resonate with physicians and caregivers, in particular, on the non-seizure benefits side, cognition, behavior, emotional and social function. And also, the broad spectrum efficacy and well-characterized safety profile enables physicians to have Epidiolex combined well with other agents, which is particularly important in this area, given polypharmacy.

We've made we expect the initial accelerated approval to be in the recurrent setting.

Amy: I'm, just going to remind people tried to limit it to one question, but on this one maybe Rob you could talk about <unk> and then Phil if you want to jump in on <unk>.

<unk> trial as you know.

As treating in the frontline setting after patients receive to bulking surgery, and radiation therapy, and that will give us an opportunity to expand to the frontline we havent given specific dates on when that would read out, but we have said it.

[Analyst]: I'm just going to remind people, try to limit it to 1 question. But on this one, maybe Rob, you could talk about 441, and then Phil, if you want to jump in on corporate development priorities.

Bruce Cozadd: I'm just going to remind people, try to limit it to 1 question. But on this one, maybe Rob, you could talk about 441, and then Phil, if you want to jump in on corporate development priorities.

Amy: Corporate development priorities.

Amy: We have initiated the <unk>, one trial, which I'll remind you is intended to be in a small number approximately 10 patients with <unk>.

Bruce Cozadd: 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.

Rob Iannone: 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.

Enrolling.

Rolling to plan.

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 this yet.

Your next question comes from Amy for Dia with Needham. Please go ahead.

Thanks for taking my question can you provide us with an update on GBP 41, where you are with <unk>.

Tommy: Yes Tommy.

Tommy: I'm, sorry, I missed.

[Analyst]: Yeah. And Tommy, I'm sorry. Let me jump to the second part of the question. So 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, create value for shareholders. We finished Q1 in a really strong financial position with $2.6 billion in cash investments, $430 million in operating cash flow in the quarter. So even after the payment of roughly $890 million net to acquire Kymerix, 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.

Phil Johnson: Yeah. And Tommy, I'm sorry. Let me jump to the second part of the question. So 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, create value for shareholders. We finished Q1 in a really strong financial position with $2.6 billion in cash investments, $430 million in operating cash flow in the quarter. So even after the payment of roughly $890 million net to acquire Kymerix, 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.

Tommy: The second part of the question.

Renee Gala: 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. And then 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 an additional initiative to help identify LGS, for example, in previously undiagnosed patients. In the adult setting, our access has been high quality and continues to improve. And then also, 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.

One study in vending might and an update on that and then just more broadly touching upon the comments previously around business development.

So for corporate development priorities are unchanged.

Tommy: We continue to look at corporate development of <unk>.

Tommy: A very important way for us to go ahead and reach more patients over time and create value for shareholders.

Have your priorities changed evolved.

In the last couple of months as we've seen the market change and if you could sort of comment on what types of assets, whether it's by the therapeutic area or the state just about it and then you'd be focused on as you think about adding something inorganically. Thank you.

Tommy: We finished the first quarter and a really strong financial position with $2 6 billion in cash and investments $430 million in operating cash flow in the quarter. So even after the payment of roughly $890 million debt to acquire <unk>. We're in a really strong position to continue to invest in our future.

I'm, just kind of remind people try to limit it to one question, but on this one maybe Rob you could talk about for one and then Phil if you want to jump in on corporate.

Tommy: 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.

Corporate development priorities.

We have initiated the <unk>, one trial, which I'll remind you is intended to be in a small number approximately 10 patients with <unk>.

Tommy: To create value we do look at both licensing like you did very successfully.

[Analyst]: We do look at both licensing, like we did very successfully with the licensing deal with Zymeworks that's brought us, obviously, Ziihera. And then obviously, with for acquisitions like we've done, we think very successfully looking forward to the upcoming PDUFA and then hopefully launch right thereafter of dordaviprone. So 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. And I would expect to see us continue to be active in this area.

Phil Johnson: We do look at both licensing, like we did very successfully with the licensing deal with Zymeworks that's brought us, obviously, Ziihera. And then obviously, with for acquisitions like we've done, we think very successfully looking forward to the upcoming PDUFA and then hopefully launch right thereafter of dordaviprone. So 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. And I would expect to see us continue to be active in this area.

Tommy: With the licensing deal with some works and this brought US obviously is our HERA and then obviously for acquisitions like we've done we've been very successful looking forward to the upcoming <unk> and hopefully launch shortly thereafter of towards <unk>. So we continue to be active in looking at opportunities see a number of them, we think that would make sense for us.

Renee Gala: So, all of those elements give us confidence in the overall growth. And of course, the durability, we've talked about having settled with our andophilers. We think we're in an excellent position there as well.

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 those data just this yet.

Yes Tommy.

I'm, sorry, I missed the second part of the question.

So for corporate development priorities are unchanged.

Rob Iannone: Your final question comes from Julie with Truist Securities. Please go ahead. Hey, thanks for squeezing me in. For the Horizon GEA, are you able to comment on the ratio of patients who are PD-1 positive? I mean, is the ratio closer to what we saw in keynote 8.1.1 or closer to your phase 1, 2, XANI plus chemo plus TISLI study? Thank you. I don't have that information. And I just would remind you that, you know, how you characterize positive depends a little bit on which assay you're using, etc. So we are measuring it, and we'll have the ability to look at that, you know, post hoc as needed to support regulatory approval.

Tommy: Across our various therapeutic areas and 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.

We continue to look at corporate development is very important.

[noise] way for US to go ahead and reach more patients over time and create value for shareholders.

[Analyst]: 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, but 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. So hopefully, that gives you some context. If we can go to the next caller, please.

Phil Johnson: 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, but 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. So hopefully, that gives you some context.

Tommy: Tariff and other policy discussions.

We finished the first quarter and a really strong financial position with $2 6 billion in cash and investments $430 million in operating cash flow in the quarter. So even after the payment of roughly $890 million debt to acquire <unk>. We are in a really strong position to continue to invest in our future.

Tommy: It does not change fundamentally what we're looking to do but 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.

Tommy: Still able to use a significant portion of that to advance our corporate development efforts. So that gives us some some context.

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.

Speaker Change: We can go to next caller please.

Bruce Cozadd: If we can go to the next caller, please.

Speaker Change: Your next question comes from our Suwanee Burma of USB UBS excuse me. Please go ahead.

Operator: Your next question comes from Ashwani Verma of UBS, excuse me. Please go ahead.

To create value we do look at both licensing like you did very successfully with the licensing deal with <unk> of this brought US obviously is our HERA and then obviously look for acquisitions like we've done we think very successful looking forward to the upcoming producer and then hopefully launched shortly thereafter of towards Alba.

Bruce Cozadd: That will conclude our question and answer session, and I will now turn the call back over to Chairman and Chief Executive Officer Bruce Cozadd for closing remarks. Thank you, operator. Let me just say with Epidiolex and Zywave 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.

Speaker Change: Oh, hi, Thanks for taking my question I just wanted to clarify so.

David Amsellem: Hi. Yeah. Thanks for taking my question. I just wanted to clarify. So 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?

Ashwani Verma: Hi. Yeah. Thanks for taking my question. I just wanted to clarify. So 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?

Speaker Change: So when you I think you mentioned that one less week of offering is that for the handful of FRS or which product is it four or is it across the business.

<unk>.

So 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 and 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.

Yes that would have been across our U S oncology business in common for the various products there.

[Analyst]: Yes. That would have been across our US oncology business and common for the various products there. Renee, anything you want to add?

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

Speaker Change: Nancy you want to add.

Nancy: Yes, that's correct.

Renée Galá: Nope. That's correct.

Renee Gala: Nope. That's correct.

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

Tariff another policy discussions.

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

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

It does not change fundamentally what we're looking to do but probably 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.

Great. Thank you for taking my question.

[Analyst]: Good. Thank you for taking my question. I have a question for you, Rob. So in our conversation with some breast cancer doctors, the interesting takeaway was that it is not a foregone conclusion that Ziihera would become first-line agent for all the HER2-positive patients. Likely, part of it is safety and comfort with the CLEOPATRA regimen. So the question is, do you see a potential for Ziihera to be the first-line as well? And what kind of trials you may have to do there because CLEOPATRA is a really long regimen here? Thank you.

Mohit Bansal: Good. Thank you for taking my question. I have a question for you, Rob. So in our conversation with some breast cancer doctors, the interesting takeaway was that it is not a foregone conclusion that Ziihera would become first-line agent for all the HER2-positive patients. Likely, part of it is safety and comfort with the CLEOPATRA regimen. So the question is, do you see a potential for Ziihera to be the first-line as well? And what kind of trials you may have to do there because CLEOPATRA is a really long regimen here? Thank you.

Speaker Change: I have a question for you Rob so in our conversations with some breast cancer doctors.

Speaker Change: The interesting takeaway was that it is not of all lung completion that.

Speaker Change: That and hope to become first line agent or.

Still able to use a significant portion of that to advance our corporate development efforts. So that gives us some some context.

Speaker Change: All the her two positive patients likely part of it is safety and comfort with the Cleopatra regimen.

We can go to next caller please.

Your next question comes from <unk> Verma of USB UBS excuse me. Please go ahead.

Speaker Change: The question is do you see a potential for that too.

Speaker Change: To be the first line as well.

Hi, Thanks for taking my question I just wanted to clarify so when you I think you mentioned that the one less week of offering is that funnel handful of FRS or which product is it four or is it across the business.

Speaker Change: And what kind of trials you may have to do that because Q about rise of nearly.

Speaker Change: Regiment hit.

Thank you.

Speaker Change: Sure well I mean, I would just reinforce our primary strategy, which is to position after in her two because of the data we've generated showing activity.

Bruce Cozadd: Sure. Well, I mean, I would just reinforce our primary strategy, which is to position after Enhertu 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 T-DM1, tucatinib, etc. So positioning it after Enhertu, 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. And there won't 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 Enhertu or would have some preexisting condition that would prevent them from.

Yes, so that would've been across our U S oncology business in common for the various products there.

Speaker Change: Very promising activity.

Speaker Change: After just about any prior and even multiple different her two agents, including standard frontline therapy, which is herceptin <unk> and chemo and her to Tdm, one two cabinet et cetera, so positioning it after in her two which is currently second line and likely to move to frontline for I would say great majority of patients in this study.

Ron anything you want to add.

Yes, that's correct.

Yeah.

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

Great. Thank you for taking my question.

I have a question for you Rob so in our conversations with some breast cancer doctors.

<unk> setting is really vary.

Speaker Change: Meaningful and there won't be any other her two therapies.

The interesting takeaways was that it is not all one confusion that.

Speaker Change: Been evaluated in that particular setting remember these patients tend to go onto multiple lines.

That in her two would become first line agent for.

Thanks therapy.

Speaker Change: You're right that there would be a few there will be some patients who may not tolerated in her two we'd have some pre existing condition that would prevent them from and I think in those cases.

All the.

Two positive patients likely part of it is safety and comfort with the Cleopatra regimen.

The question is do you see a potential for that too.

Bruce Cozadd: And I think in those cases, a patient who's either progressed on or intolerant to Enhertu could move on to zanidatamab based on the 303 trial. If Enhertu 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.

Speaker Change: Patient who's either progressed on or intolerant and her two could move on to <unk> based on the 303 trial.

To be the first line as well.

And what kind of trials you may have to do that because <unk> really.

Regiment here.

Speaker Change: If if.

<unk>.

Speaker Change: Her too.

Sure.

Speaker Change: Okay.

Speaker Change: As is.

Reinforce our primary strategy, which is to position after and heard too because of the data we've generated showing activity is very promising activity.

Speaker Change: Ultimately approve new frontline setting I do think it will be the great majority of patients who get it based on the strong efficacy.

After just about any prior and even multiple different her two agents, including standard frontline therapy, which is herceptin progenitor chemo and her to tdm, one to cabinet et cetera. So positioning it after in her two which is currently second line and likely to move to frontline for I would say great majority of patients in this deal.

Sean <unk>: Your next question comes from Sean <unk> of Morgan Stanley. Please go ahead.

Operator: Your next question comes from Sean Lallman of Morgan Stanley. Please go ahead.

Speaker Change: Hi, This is Mike <unk> on for Sean Lehmann. Thank you for taking our question.

[Analyst]: Hi. This is Mike Riadon for Sean Lallman. Thank you for taking our question. For Xywav and narcolepsy, are you able to provide a more granular breakout for patients need oxybate versus high sodium switches? And then in IH, how are you thinking about Xywav's value proposition with potential for a competitive threat there from Lumryz? Thank you. Renee?

Mike Riordan: Hi. This is Mike Riadon for Sean Lallman. Thank you for taking our question. For Xywav and narcolepsy, are you able to provide a more granular breakout for patients need oxybate versus high sodium switches? And then in IH, how are you thinking about Xywav's value proposition with potential for a competitive threat there from Lumryz? Thank you.

Sean <unk>: <unk>.

Sean <unk>: And narcolepsy are you able to provide a more granular breakout for patients from your docs debate versus high surgeon switches and then NIH. How are you thinking about <unk> value proposition.

<unk> setting is really vary.

Meaningful and there won't be any other her two therapies that will have been evaluated in that particular setting remember these patients tend to go on to get multiple lines.

Sean <unk>: The potential for a competitive threat there from the rise. Thank you.

Bruce Cozadd: Renee?

Sean <unk>: Renee.

Therapy.

Speaker Change: Yeah, so with respect to the narcolepsy as we have seen primarily adds in the quarter coming from new to Oxidate patients and I think that does speak to what we're now starting to see which is a bit of an expansion to.

Youre right that there would be a few there will be some patients who may not tolerated her to or would have some pre existing condition that would prevent them from and I think in those cases.

Renée Galá: Yeah. So with respect to the narcolepsy adds, we have seen primarily adds in the quarter coming from new-to-oxybate patients. And 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. And 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. So 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 Lumryz, I would say, again, Xywav is the only low-sodium option.

Renee Gala: Yeah. So with respect to the narcolepsy adds, we have seen primarily adds in the quarter coming from new-to-oxybate patients. And 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. And 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. So 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 Lumryz, I would say, again, Xywav is the only low-sodium option.

Patient who's either progressed on or intolerant to inherit two could move on to <unk> based on the 303 trial.

Speaker Change: The market given that this is a more.

If if.

Speaker Change: Mature product we've been really pleased.

And her too.

As is.

Speaker Change: With what we're seeing in terms of both field execution.

Ultimately approved in the frontline setting I do think it will be the great majority of patients who get it based on the strong efficacy.

Speaker Change: Appreciation of low sodium to physicians.

Speaker Change: And also to patients and that's really resonating, it's clear that hcp's and patients are prioritizing long term health benefits of low sodium as well as to dosing flexibility that <unk> offers so we do see switching to a shifting over to IH, we do see.

Your next question comes from Sean <unk> of Morgan Stanley. Please go ahead.

Hi, This is Mike <unk> on for Sean Lehmann. Thank you for taking our question.

<unk> in narcolepsy are you able to provide a more granular breakout for patients new to oxy based versus high surgeon switches and then NIH. How are you thinking about <unk> value proposition with potential for a competitive threat there from numerous thank you.

Speaker Change: H as the area, where there's the most opportunity to drive growth with.

Speaker Change: With respect to any future potential competition NIH from loom rise I would say again <unk> is the only low sodium option and we do know from the data that we have been able to generate we know that narcolepsy Nia.

Renee.

Yeah, so with respect to the narcolepsy.

As we have seen primarily adds in the quarter coming from new to Oxidate patients and 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.

Renée Galá: 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're quite well positioned with respect to narcolepsy and idiopathic hypersomnia.

Renee Gala: 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're quite well positioned with respect to narcolepsy and idiopathic hypersomnia.

Speaker Change: Which patients are at increased risk for cardiovascular comorbidities relative to the general population and so we do continue to see also a high sodium oxidate patients as potential valuation patients and keep in mind that within our label for <unk> for idiopathic hyper.

Mature product we've been really pleased.

With what we're seeing in terms of both field execution.

Appreciation of the low sodium to physicians.

Speaker Change: Sameer there is flexible dosing that indication is twice nightly or once nightly depending on what the physician and the patient choose.

And also to patients and that's really resonating, it's clear that hcp's and patients are prioritizing long term health benefits of low sodium as well as the dosing flexibility that <unk> offers so we do see switching to a shifting over to IH, we do see.

Speaker Change: Due to pursue in terms of their therapy. So we feel we're quite well positioned with respect to narcolepsy and idiopathic hypersomnia.

Speaker Change: I will also just jumped in and point out that.

IH as the area, where there's the most opportunity to drive growth.

[Analyst]: 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 don't 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. So I totally agree with everything Renee said in terms of potential competitive positioning and differences between the product. But there's some room to go before we actually do have competition in IH.

Bruce Cozadd: 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 don't 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. So I totally agree with everything Renee said in terms of potential competitive positioning and differences between the product. But there's some room to go before we actually do have competition in IH.

Speaker Change: For those of you this saw the.

Speaker Change: Court decisions today.

With respect to any future potential competition NIH from loom rise I would say again <unk> is the only low sodium option and we do know from the data that we have been able to generate we know is that narcolepsy Nia.

Speaker Change: Given that our IP has been found to be valid that avid has admitted to infringing it.

Speaker Change: We still don't see even after today's ruling a viable path for avid older commercialized Bloom horizon IH before the expiration of the relevant patent in 2036, so I totally agree with everything <unk> said in terms of potential.

<unk> patients are at increased risk for cardiovascular comorbidities relative to the general population and so we do continue to see all the high sodium oxidate patients as <unk>.

Speaker Change: Competitive positioning and differences between the product, but it's theirs.

Speaker Change: There are some <unk>.

<unk> <unk> patients and keep in mind that within our label for <unk> for idiopathic hypersomnia. There is flexible dosing that indication is twice nightly or once nightly depending on what the physician and the patient choose to tip.

Some room to go before we actually do have competition IH.

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

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

Gary Nachman: Thanks, and good afternoon.

Gary Nachman: So first I hear in DTC understanding is a small indication how is the ramp going how rapid is the penetration and.

Jessica Fye: Thanks, and good afternoon. So for Ziihera and BTC, understanding it's a small indication, how is the ramp going? How rapid is the penetration? And what's the anecdotal feedback on how the drug is performing? And have there been any challenges with access and how you're helping facilitate that? And then if GEA ends up being positive in first line as a bigger market, would you consider changes to pricing at all? And also, how your promotional efforts would change for that indication versus BTC? Thanks.

Gary Nachman: Thanks, and good afternoon. So for Ziihera and BTC, understanding it's a small indication, how is the ramp going? How rapid is the penetration? And what's the anecdotal feedback on how the drug is performing? And have there been any challenges with access and how you're helping facilitate that? And then if GEA ends up being positive in first line as a bigger market, would you consider changes to pricing at all? And also, how your promotional efforts would change for that indication versus BTC? Thanks.

So in terms of their therapy. So we feel we're quite well positioned with respect to narcolepsy and idiopathic hypersomnia.

Gary Nachman: What's the anecdotal feedback on how the drug is performing.

Gary Nachman: And have there been any challenges with access and how you're helping facilitate that.

I will also just jumped in and point out that.

For those of you this saw the.

Gary Nachman: And then.

Gary Nachman: If <unk> ends up being positive.

Court decisions today.

Gary Nachman: <unk> is a bigger market would you consider changes to pricing at all and also how your promotional efforts.

Given that our IP has been found to be valid that avid al has admitted to infringing it.

Gary Nachman: What changed for that indication versus BTC. Thanks.

We still don't see even after today's ruling a viable path for avid older commercialized Bloom horizon IH before the expiration of the relevant patent in 2036, so I totally agree with everything <unk> said in terms of potential.

Gary Nachman: Okay. Thanks for the question. So we had our first patients treated in December shortly after launch for BTC and the reception has been quite positive.

Renée Galá: Yeah. Thanks for the question. So we had our first patients treated in December shortly after launch for BTC, and the reception has been quite positive. HCPs are glad to have Ziihera available to treat patients. Just as a reminder, BTC is a very small patient population, 3,000 patients in the US in first-line and second-line. And 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.

Renee Gala: Yeah. Thanks for the question. So we had our first patients treated in December shortly after launch for BTC, and the reception has been quite positive. HCPs are glad to have Ziihera available to treat patients. Just as a reminder, BTC is a very small patient population, 3,000 patients in the US in first-line and second-line. And 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.

Gary Nachman: There are glad to have zahara available to treat patients just as a reminder, BTC is a very small patient population 3000 patients in the U S. In first line and second line.

Competitive positioning and differences between the product, but it's theirs.

There are some.

Some room to go before we actually do have competition IH.

Gary Nachman: And therefore, we do expect revenues from this first indication is as we've stated to be quite modest.

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

Gary Nachman: In terms of access we haven't really had any issues.

Thanks, and good afternoon.

So first I hear in DTC understanding is a small indication how is the ramp going how rapid is the penetration and what's the anecdotal feedback on how the drug is performing.

Gary Nachman: Sure.

Gary Nachman: And in the process of doing is ensuring we spent quite a lot of time in these first few months, ensuring that we have agreements of the necessary.

Gary Nachman: Logistics in place for community and academic centers to be able to get access to their product rapidly and certainly the the efficacy supporting this approval is something that they are excited to be able to bring to patients when we look at gea.

And have there been any challenges with access and how you're helping facilitate that.

And then if <unk> ends up being positive in first line is a bigger market would you consider changes to pricing at all and also how your promotional efforts.

Renée Galá: And 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. So stay tuned. But we think, given the benefit that we are seeing in efficacy, we'll be in a good position where we are today.

Renee Gala: And 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. So stay tuned. But we think, given the benefit that we are seeing in efficacy, we'll be in a good position where we are today.

Change for that indication versus BTC. Thanks.

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.

Okay. Thanks for the question. So we had our first patients treated in December shortly after launch for PTC and the reception has been quite positive hcp's. There are glad to have <unk> hara available to treat patients just as a reminder, BTC is a very small patient.

Gary Nachman: Intend to go rapidly towards again trying to get NCC guidelines in place similar to what we intend to do relative to <unk> of course, we would not.

<unk> 3000 patients in the U S. In first line and second line and therefore, we do expect revenues from this first indication is as we've stated to be quite modest.

Gary Nachman: Without having an approval, but having the product on MCC and guidelines will enable us for that indication should physicians choose to do so I think with respect to pricing. We are in a good position, we typically will comment on pricing when we have.

In terms of access we haven't really had any issues.

Sure.

And in the process of doing is ensuring we spent quite a lot of time in these first few months, ensuring that we have agreements that the necessary logistics in place for community and academic centers to be able to get access to their product rapidly and certainly.

Gary Nachman: Launch slash approval.

Gary Nachman: They tuned, but we think given the benefit that we're seeing in efficacy will be in a good position, where we are today.

Gary Nachman: Okay.

Gary Nachman: Yeah.

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

The the efficacy supporting this approval is something that they're excited to be able to bring to patients when we look at gea.

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

Gary Nachman: Perfect.

Charles Duncan: On for Charles Thank you for taking our questions.

David Amsellem: I'm for Charles. Thank you for taking our questions. So you reiterated confidence in Epidiolex reaching blockbuster status in 2025. Can you speak about any catalysts or what market dynamics underpin that expectation? And also, can you talk about any meaningful changes in the US or in off-label usage that could contribute to this trajectory? Thank you.

[Analyst] (Cantor Fitzgerald): I'm for Charles. Thank you for taking our questions. So you reiterated confidence in Epidiolex reaching blockbuster status in 2025. Can you speak about any catalysts or what market dynamics underpin that expectation? And also, can you talk about any meaningful changes in the US or in off-label usage that could contribute to this trajectory? Thank you.

Speaker Change: So you reiterated confidence in <unk>, reaching blockbuster status in 2025 can you speak about any catalyst or what market dynamics underpin that expectation and also can you talk about any meaning.

Excited to be able to read out that study in the second half with that data and with publication of that data we would.

Ken can go rapidly towards again trying to get NCC guidelines in place similar to what we intend to do relative to <unk> of course, we would not.

The U S R and off label usage that could contribute to this trajectory. Thank you.

Remote without having an approval, but having the product on MCC and guidelines will enable us for that indication should physicians choose to do so I think with respect to pricing. We are in a good position, we typically will comment on pricing when we have.

Renee: Yes Renee.

[Analyst]: Yeah. Renee?

Bruce Cozadd: Yeah. Renee?

Speaker Change: Yes, I didn't hear the full question.

Renée Galá: Yeah. I didn't hear the full question, but what I understood was wanting to say that there's a trajectory.

Renee Gala: Yeah. I didn't hear the full question, but what I understood was wanting to say that there's a trajectory.

Speaker Change: What I understood was one I can jump I can jump in on.

Speaker Change: 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 grade.

[Analyst]: 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.

Bruce Cozadd: 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.

A launch slash approval, so stay tuned, but we think given the benefits that we're seeing in efficacy.

Speaker Change: Right.

It's already 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.

I'll be in a good position, where we are today.

Speaker Change: Renee you can comment on where growth can be coming from but we're very solidly on track.

Okay.

Yeah.

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

Renee: Yeah. Thanks for the call had cut out for me. So we are quite.

Renée Galá: Yeah. Thanks, Bruce. The call had cut out for me. So 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. And that data continues to resonate with physicians and caregivers, in particular on the non-seizure benefits side: cognition, behavior, emotional, and social function. And also, the broad-spectrum efficacy and well-characterized safety profile enables physicians to have Epidiolex combined 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.

Renee Gala: Yeah. Thanks, Bruce. The call had cut out for me. So 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. And that data continues to resonate with physicians and caregivers, in particular on the non-seizure benefits side: cognition, behavior, emotional, and social function. And also, the broad-spectrum efficacy and well-characterized safety profile enables physicians to have Epidiolex combined 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.

Yes.

Renee: Confident in where we're going with respect to the future at the dialects as a highly differentiated product within the ASN landscape.

On for Charles Thank you for taking our questions.

You reiterated confidence in <unk>, reaching blockbuster status in 2025 can you speak about any catalyst or what market dynamics underpin that expectation and also can you talk about any meaning.

Renee: Have a robust body of evidence supporting that both on the seizure side as well as the non seizure benefits and that data continues to resonate with physicians and caregivers in particular on the non seizure benefits side cognition behavior emotional and social function and also the broad spectrum efficacy in <unk>.

The U S R and off label usage that could contribute to this trajectory. Thank you.

Yes.

Yes Renee.

Speaker Change: Well characterized safety profile enables physicians to have at the dialects combined well with other agents, which is particularly important in this area getting given polypharmacy, while we do not promote off label, we do see the product used across a number of different epilepsy subtype.

Yes, I didn't hear the full question, but what I understood was one I can jump in if I can jump in on I.

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 trade.

Okay.

Speaker Change: Across the underlying seizures for which we've shown efficacy and then in terms of additional growth, we're having great momentum in the adult in long term care setting we.

It's already 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.

Renée Galá: And then 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 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. And then also, 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. So all of those elements give us confidence in the overall growth. And of course, the durability we've talked about having settled with our ANDA filers, we think we're in an excellent position there as well.

Renee Gala: And then 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 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. And then also, 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. So all of those elements give us confidence in the overall growth. And of course, the durability we've talked about having settled with our ANDA filers, we think we're in an excellent position there as well.

Renee you can comment on where the growth can be coming from but we're very solidly on track.

Speaker Change: We havent do screening tool that we've put into.

Speaker Change: That we've launched and additional initiatives to help identify LG asks for example in previously undiagnosed patients in the adult setting our access has been high quality and continues to improve and then also with respect to our nurse Navigator program, we're seeing strong persistency.

Yes, thanks for the call had cut out for me. So we are quite quite confident in where we're going with respect to the future <unk> is a highly differentiated product within the ASM landscape.

Have a robust body of evidence supporting that both on the seizure side as well as the non seizure benefits and that data continues to resonate with physicians and caregivers in particular on the non seizure benefits side cognition behavior emotional and social function and also the broad spectrum efficacy and well.

And seeing that even.

Speaker Change: Become stronger with respect to the nurse navigator program, helping to guide patients starting therapy. So all of those elements give us.

Speaker Change: Confidence in the overall growth and of course, the durability, we've talked about having settled with our Anda filers. We think we're in an excellent position there as well.

I'll characterize safety profile enables physicians to have at the dialects combined well with other agents, which is particularly important in this area getting given polypharmacy, while we do not promote off label, we do see the product used across a number of different epilepsy subtype.

Speaker Change: Your final question comes from Julie with True Securities. Please go ahead.

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

Speaker Change: Thanks for squeezing me in for the Horizon Gea are you able to comment on the ratio of patients who are PD lone positive.

Across the underlying seizures for which we have shown efficacy and then in terms of additional growth, we're having great momentum in the adult in long term care setting.

Bruce Cozadd: Hey. Thanks for squeezing me in. For the HERIZON-GEA-01, are you able to comment on the ratio of patients who are PD-1 positive? I mean, is the ratio closer to what we saw in KEYNOTE-811 or closer to your phase 1, 2, zanidatamab plus chemo plus tislelizumab study? Thank you.

Joon Lee: Hey. Thanks for squeezing me in. For the HERIZON-GEA-01, are you able to comment on the ratio of patients who are PD-1 positive? I mean, is the ratio closer to what we saw in KEYNOTE-811 or closer to your phase 1, 2, zanidatamab plus chemo plus tislelizumab study? Thank you.

It's a ratio closer to what we saw in keynote one one or closer to your phase one and two is there any plus chemo plus typically study. Thank you.

We have a new screening tool that we've put into that.

We've launched additional initiatives to help identify LG asks for example in previously undiagnosed patients in the adult setting our access has been high quality and continues to improve and then also with respect to our nurse Navigator program, we're seeing strong persistency.

Speaker Change: I don't have that information and I, just would remind you that.

Operator: 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. So we are measuring it, and we'll have the ability to look at that post-hoc as needed to support regulatory approval.

Bruce Cozadd: 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. So we are measuring it, and we'll have the ability to look at that post-hoc as needed to support regulatory approval.

Speaker Change: How you characterize positive depends a little bit on which asset you are using et cetera. So we are measuring it and we will have the ability to look at that post hoc as needed to support regulatory approval.

And seeing that even.

That becomes stronger with respect to the nurse navigator program, helping to guide patients starting therapy. So all of those elements give us.

Speaker Change: That will conclude our question and answer session and I will now turn the call back over to Chairman and Chief Executive Officer, Bruce <unk> for closing remarks.

Operator: 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.

Speaker Change: Thank you operator, let me just say with <unk> XI way of growth some upcoming exciting approvals on the oncology side of our business.

Confidence in the overall growth and of course the dirt.

[Analyst]: Thank you, operator. Let me just say, with Epidiolex and Xywav's 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.

Bruce Cozadd: Thank you, operator. Let me just say, with Epidiolex and Xywav's 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.

Our ability we've talked about having settled with our Anda filers, we think we're in an excellent position there as well.

Speaker Change: Across three different products and gea data upcoming Theres a lot to look forward to.

Your final question comes from Julie with true <unk> Securities. Please go ahead.

Speaker Change: 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.

Thanks for squeezing me in.

<unk> are you able to comment on the ratio of patients who are PD lone positive.

Ratio closer to what we saw in keynote <unk> 811 or closer to your phase <unk>, plus chemo plus particularly study. Thank you.

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

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

I don't have that information and I, just would remind you that.

How you characterize positive depends a little bit on which asset you are using et cetera. So we are measuring it and we will have the ability to look at that post hoc as needed to support regulatory approval.

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

Thank you operator, let me just say with <unk> XI way of growth some upcoming exciting approvals on the oncology side of our business.

<unk> three different products and gea data upcoming Theres a lot to look forward to.

I'd 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.

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

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Yes.

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Q1 2025 Jazz Pharmaceuticals PLC Earnings Call

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