Jazz Pharmaceuticals - Earnings Call - Q2 2025

Executive Summary

• Q2 2025 revenue was $1.046B, up 2% year over year; non‑GAAP diluted EPS was $(8.25) driven by a $905.4M acquired IPR&D charge tied to dordaviprone, which impacted results by ~$14.75 per share.
• Sleep portfolio strength continued: Xywav net sales rose 13% YoY to $415.3M with robust net patient adds (+625 QoQ; 15,225 active) across narcolepsy and IH; Epidiolex grew 2% YoY to $251.7M amid U.S. inventory dynamics.
• Oncology faced headwinds (Zepzelca −8% YoY to $74.5M; Rylaze −7% YoY to $100.7M), but multiple near‑term catalysts remain: Zepzelca priority review for 1L ES‑SCLC (PDUFA Oct 7, 2025), HERIZON‑GEA‑01 top‑line in 4Q25, and Modeyso (dordaviprone) PDUFA Aug 18 (FDA approval announced Aug 6).
• Guidance narrowed: total revenue $4.15–$4.30B (lowered top end), SG&A and R&D ranges reduced, non‑GAAP tax rate lowered to 27–37%, and non‑GAAP EPS raised at the low end to $4.80–$5.60; GAAP outlook incorporates the IPR&D expense and litigation settlements.
• Leadership transition: Renee Galá named President & CEO effective Aug 11; management emphasized diversified growth drivers and upcoming regulatory catalysts as stock‑reaction narrative points.

What Went Well and What Went Wrong

What Went Well

• Xywav momentum: net sales +13% YoY to $415.3M; net patient adds ~625 QoQ; “Xywav remains the only low‑sodium oxybate … and the only FDA‑approved therapy to treat IH”.
• Epidiolex demand: net sales +2% YoY to $251.7M despite inventory dynamics; management “remain[s] confident in achieving blockbuster status in 2025”.
• Pipeline/regulatory setup: Zepzelca sNDA priority review for 1L ES‑SCLC maintenance (PDUFA Oct 7) and HERIZON‑GEA‑01 top‑line in 4Q25; “potentially practice‑changing” IMforte data submitted to NCCN.

Quotes:

• Bruce Cozadd: “We remain confident in the outlook … driven by multiple anticipated near‑term oncology catalysts … PDUFA dates for dordaviprone and Zepzelca”.
• Renée Galá: “XiWave delivered another strong quarter … benefits of low sodium and individualized dosing continue to resonate”.
• Robert Iannone: IMforte showed reduced risk of progression or death by 46% and risk of death by 27% vs atezolizumab alone; “practice changing”.

What Went Wrong

• Non‑GAAP loss/EPS miss driven by accounting: acquired IPR&D expense of $905.4M for dordaviprone weighed on GAAP and non‑GAAP results (per‑share impact ~$14.75).
• Oncology pressure: Zepzelca −8% YoY due to 2L competition and protocol changes delaying 1L limited‑stage patients’ progression to 2L; Rylaze −7% YoY with pediatric protocol shifts reducing class usage vs pre‑implementation levels.
• SG&A mix and cost headwinds: GAAP SG&A rose to $358.4M (34.3% of revenue), reflecting higher compensation and portfolio support; non‑GAAP SG&A $310.3M (29.7%).

Transcript

Speaker 1

Today, and thank you for standing by. Welcome to Jazz Pharmaceuticals' 2025 second quarter earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press *11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press *11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Jack Spinks, Executive Director of Investor Relations.

Speaker 9

Thank you, Operator, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its second quarter 2025 financial results. The slide presentation accompanying this webcast is available on the Investors 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 and recently announced Chief Executive Officer, effective August 11, Rob Iannone, Executive Vice President, Global Head of R&D and Chief Medical Officer, and Philip Johnson, Executive Vice President and Chief Financial Officer.

On slide two, I'd like to remind you that today's webcast includes forward-looking statements, such as those related to our future financial and operating results, growth potential, and anticipated development, regulatory, and commercial milestones and goals, which involve risks and uncertainties that could cause actual events, performance, and results to differ materially from those contained in those forward-looking statements.

We encourage you to review the statements contained in today's press release, in our slide deck, and the risks and uncertainties described under the 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 fiscal quarter ended June 30, 2025, which identifies certain factors that may cause the company's actual events, performance, and results to differ materially from those contained in the forward-looking statements made on today's webcast. We undertake no duty or obligation to update our forward-looking statements. As noted on slide three, we will discuss non-GAAP financial measures on this webcast. Descriptions of these non-GAAP financial measures and reconciliations of GAAP to non-GAAP financial measures are included in today's press release and the slide presentation available on the Investors section of our website.

I'll now turn the call over to Bruce.

Speaker 0

Thanks, Jack. Good afternoon, everyone. Thank you for joining us today to discuss Jazz's second quarter 2025 results. Starting on slide five, I'd like to congratulate Renee on her unanimous selection by the Jazz Board of Directors as President and CEO. I'm confident Renee is the right leader to build on Jazz's momentum and serve as a catalyst in driving long-term growth. After working with Renee closely for more than five years, I've seen firsthand that she has the right skill set and experience to further drive innovation while nurturing the culture of purpose and patient impact that is at the center of everything we do at Jazz. Since co-founding Jazz in 2003, I've had the extraordinary privilege of leading the company through its growth and significant diversification that has transformed the business into the fully integrated biopharma company it is today.

I'll continue serving as Chairman of the Board of Directors, providing strategic guidance, and look forward to seeing Jazz continue delivering for patients, employees, and shareholders. Now, turning to slide six, Jazz continues to demonstrate considerable progress across commercial, R&D, and corporate development. We remain confident in the strength of our diversified portfolio and excited about the potential for future growth as we prepare for the anticipated approval of Dirudavaprom and approval of Zepzelca in an earlier line of treatment. We're approaching a significant milestone for Dirudavaprom with the upcoming FDA PDUFA target action date of August 18th. We added Dirudavaprom to our pipeline through the Chimerics acquisition we closed in April, enhancing our presence in rare oncology.

Given its patent protection into 2037, with potential to receive patent term extensions and the opportunity for expanded use in the frontline setting, we view Dirudavaprom as a meaningful and durable revenue opportunity for Jazz. In addition, we have the right capabilities in place to deliver a successful commercial launch and are positioned to initiate key activities immediately upon receiving FDA approval. We remain excited about bringing this first-in-class therapy to patients with H3K27M mutant diffuse glioma, who currently have very limited treatment options. Additionally, on the regulatory front, I'm pleased that Zyhera was recently granted conditional marketing authorization by the European Commission for advanced HER2-positive biliary tract cancer, or BTC, and we look forward to the upcoming October 7 PDUFA target action date for Zepzelca in first-line maintenance for extensive stage small cell lung cancer.

Turning to our commercial business, in the second quarter of 2025, we generated over $1 billion in total revenue across our portfolio led by our neuroscience assets. Xywav grew 13% year over year with robust net patient adds seen across both narcolepsy and idiopathic hypersomnia, or IH. Xywav remains the only low-sodium oxybate, the number one branded treatment for narcolepsy as measured by revenue, and the only FDA-approved therapy to treat IH. Epidiolex continues to have strong underlying demand, and we remain confident in its blockbuster potential.

While our oncology portfolio is facing near-term headwinds, we remain confident in the outlook for growth driven by multiple near-term catalysts, including the upcoming Dirudavaprom PDUFA for the treatment of recurrent H3K27M mutant diffuse glioma, Zepzelca's potential move into first-line maintenance in extensive stage small cell lung cancer, and the top-line data readout from Zanidatamab's phase 3 first-line gastroesophageal adenocarcinoma, or GEA, trial expected late in the fourth quarter of 2025. Turning to our pipeline, at the ASCO annual meeting in June, we presented potentially practice-changing phase 3 data for Zepzelca and updated phase 2 data, including long-term survival, for Zanidatamab, which demonstrated unprecedented advances in their respective tumor types. Our Zanidatamab clinical development program continues to progress well and enroll patients across our numerous ongoing registrational trials. Additionally, we initiated a new phase 2 trial in neoadjuvant and adjuvant HER2-positive breast cancer.

With the first half of the year complete, we've revised our financial guidance, including a modest reduction in the midpoint of our revenue guidance, while reductions in SG&A, R&D, and effective tax rate guidance support raising the lower end of our ANI/NEPS guidance. We generated robust operating cash flow in the first half of the year and remain confident in the overall strength of the business. In summary, we're focused on execution and delivering innovative therapies for patients and their families. Our diversified portfolio, robust pipeline, and disciplined approach to capital allocation position us well for sustainable long-term growth. 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'll open the call to Q&A. Renee?

Speaker 1

Thanks, Bruce. I'm thrilled to be stepping into the CEO role to build upon Jazz's incredible success and transformation over the last several years. I'd like to thank the Board for their trust and confidence in me, and Bruce for his dedicated leadership of Jazz over the past two decades. I believe this company has immense potential, and I look forward to continuing the important efforts underway and working with our team to drive greater value for our patients and shareholders. I know there may be questions about potential changes to Jazz's future direction. Right now, my focus is on ensuring a smooth transition into the CEO role. As we shape our next phase of growth, I plan to listen and gather insights from a broad range of internal and external voices, and as decisions are made, they will be shared broadly.

In the meantime, I appreciate your patience and support, and I look forward to engaging on this topic in the future. Now, I'll begin on slide eight to discuss the progress of our commercial portfolio. Starting with our sleep therapeutic area, total sleep revenue, which includes Xywav and Xyrem net product sales, plus royalties from high-sodium oxybate authorized generics, or AGs, was $505 million in the second quarter of 2025. Xywav delivered another strong quarter, with net product sales increasing 13% year over year to approximately $415 million. As the only low-sodium oxybate therapy, the benefits of Xywav in reducing sodium intake and individualized dosing continue to resonate with patients and HCPs. This is reflected by the approximately 625 net patient adds across both narcolepsy and idiopathic hypersomnia exiting the second quarter.

We continue to focus on strong execution and enabling as many patients as possible to benefit from low-sodium Xywav. Our field teams are generating strong demand, with medical science liaisons and a suite of patient services like field nurse educators working in an integrated fashion to educate HCPs and help patients from their initial diagnosis through titration of Xywav. We've been particularly pleased with the continued momentum in idiopathic hypersomnia, where we had approximately 400 net patient adds this quarter. Our consumer-targeted digital and media campaigns are performing well and building disease awareness and patient education. These initiatives, coupled with our ongoing HCP education around proper diagnosis and identifying appropriate patients who can benefit from Xywav, are contributing meaningfully to growth in IH, where Xywav is the only FDA-approved therapy.

We were pleased with our robust medical presence at the APSS annual meeting in June, with 24 total presentations, including 19 posters and five oral presentations. These included results from the phase 4 open-label Xylo trial, showing that a switch from high-sodium oxybate to the same dose of low-sodium oxybate was associated with clinically meaningful reductions in blood pressure. Additionally, two presentations from the Duet trial evaluating sleep architecture demonstrated the effectiveness of Xywav on improvements in sleep quality among patients with IH or narcolepsy. These data presentations continue to strengthen the clinical evidence supporting Xywav's differentiated therapeutic value. Moving to slide nine, underlying demand for Epidiolex remains strong, with second-quarter net product sales of approximately $252 million, representing a 2% increase compared to the same quarter in 2024. Year-over-year revenue growth was impacted by a number of factors, including U.S. inventory dynamics.

As noted on a prior call, we experienced an earlier-than-expected build of inventory in the second quarter of 2024, which negatively impacts our current year-over-year growth rate. Based on typical seasonality, we anticipate a gradual build of inventory throughout the second half of this year. Our Epidiolex field teams in the U.S. and Europe are executing well, focusing on the product's unique differentiation, including the robust body of evidence supporting both seizure and non-seizure benefit. The adult segment and long-term care facilities continue to be a focus of growth for Epidiolex. LGS has historically been underdiagnosed in adult patients due to the evolution of symptoms over time. However, the refractory epilepsy screening tool for LGS is helping some providers to more readily identify adult patients living with LGS. With our ongoing momentum, we continue to expect Epidiolex to reach blockbuster status this year.

Moving to oncology on slide 10, Rylaze's net product sales were approximately $101 million in the second quarter of 2025, a decrease of 7% year over year. Updates to Children's Oncology Group pediatric ALL treatment protocol that impacted the timing of asparaginase administration, which were first recommended a year ago, have been broadly adopted. Although claims data indicate that pediatric asparaginase use as a class remains below pre-protocol implementation levels, Rylaze's use in pediatric ALL patients relative to the asparaginase class as a whole has remained broadly stable. We are focused on continuing efforts to ensure switching to Rylaze at the first sign of hypersensitivity reaction and expanding our presence in the adolescent and young adult market. We view these as the greatest opportunities for Rylaze's growth.

On slide 11, Zepzelca net product sales for the second quarter of 2025 were approximately $75 million, a decrease of 8% year over year. While we have seen increased competition in the second-line small cell lung cancer setting, Zepzelca continues to be a highly prescribed treatment for patients. Of note, the adoption of immunotherapy in first-line limited stage small cell lung cancer is improving PFS and delaying the progression of patients into the second-line setting, thereby reducing the number of patients available for second-line treatment. Importantly, we believe the Enforte data presented at ASCO will set a new treatment standard for extensive stage small cell lung cancer patients in the first-line maintenance setting.

Our SNDA has been granted priority review with the PDUFA target action date of October 7, 2025, and we have submitted the data for potential inclusion in NCCN guidelines, which is generally a path for broader uptake and reimbursement. This potential to move into first-line maintenance therapy represents an important opportunity to enable patients to benefit from Zepzelca earlier in their treatment and represents an opportunity to redefine the treatment paradigm in first-line extensive stage small cell lung cancer. Moving to slide 12 and Zyhera, we recognized approximately $6 million of net product sales in the second quarter of 2025, which, given the patient population and biliary tract cancer, is aligned to our expectations at this early stage of launch. We are receiving feedback from oncologists that continues to confirm the real-world clinical profile and benefit matches what was observed in clinical trials.

We're pleased with this positive feedback as HCPs gain experience and confidence with prescribing Zyhera. As we look ahead to GEA, we would anticipate rapid NCCN guideline inclusion if data are positive and strong clinical adoptions following potential regulatory approval. We believe Zanidatamab has the potential to be the HER2-targeted agent of choice. Finally, we were pleased the European Commission granted conditional marketing authorization for second-line HER2-positive biliary tract cancer in June, and we are initiating the rolling launch across Europe. I'll now turn it over to Rob for an update on our pipeline and upcoming milestones. Rob?

Speaker 4

Thank you, Renee. Starting on slide 14, we have an exciting pipeline and are making substantial progress on key programs with additional milestones expected this year. In oncology, we were pleased the FDA granted priority review of our sNDA for Zepzelca with a PDUFA target action date of October 7 for maintenance therapy in first-line extensive stage small cell lung cancer for patients who have not progressed during induction chemotherapy. The submission was based on the compelling phase 3 ENFORCE data presented at ASCO. We believe these results are practice-changing, and we have submitted the data for potential inclusion in NCCN guidelines. Regarding our phase 3 first-line Horizon GEA Zanidatamab trial, given that we're now in early August, we do not expect to announce top-line data in the third quarter.

Based on the current event projections, we do continue to expect we will announce top-line data late in the fourth quarter of 2025, consistent with our prior disclosure of the second half of 2025. We are also excited to highlight the recently initiated phase 2 trial studying Zanidatamab as neoadjuvant and adjuvant therapy in breast cancer. This trial aims to reduce the burden on patients with early breast cancer, increase pathologic complete response rates, improve long-term outcomes, and reduce overall toxicity. The randomized open-label trial will assess the pCR rate of neoadjuvant Zanidatamab and taxane, with or without carboplatin, versus a regimen containing a taxane, carboplatin, and trastuzumab and pertuzumab. Following surgery, patients with a pCR will continue on Zanidatamab, and those without a pCR will receive T-DM1 as adjuvant therapy and will be followed for event-free survival.

Turning to our Zanidatamab development program on slide 15, the ongoing clinical trials continue to progress, and we're expanding the program with the new trial in neoadjuvant and adjuvant breast cancer. The phase 3 EMPOWER BC-303 trial evaluating Zanidatamab plus physician's choice of chemotherapy versus trastuzumab plus physician's choice of chemotherapy in metastatic breast cancer patients who are intolerant to or have progressed on T-DXd treatment continues to progress well with enrollment and strong interest from sites. Our first-line confirmatory BTC trial also continues to advance, as does the phase 2 pan tumor trial. Moving to slide 16, we were pleased to close the Chimerics transaction in April and welcome our new colleagues to Jazz.

We look forward to the upcoming PDUFA target action date of August 18 for Dirudavaprom, 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, and the opportunity to bring hope to patients who currently have no approved drug therapies. The confirmatory action trial in the frontline setting is ongoing, and enrollment remains on track. We are continuing to assess timelines for the trial and will provide an update as appropriate. Our current focus is on the NDA for Dirudavaprom and potentially bringing this therapy to patients as soon as possible. This represents exactly the kind of transformative innovation we strive to deliver for patients at Jazz. We intend to host an investor webcast to discuss the commercial launch of Dirudavaprom following approval.

Now, turning to slide 17, I'll highlight the encouraging data we presented at ASCO this year that support my confidence in our pipeline. In results from the phase 3 Enforte trial, which have been published in The Lancet, Zepzelca in combination with atezolizumab demonstrated a reduced risk of disease progression or death from the time of randomization by 46% and the risk of death by 27% compared to atezolizumab alone. In addition, the treatment duration for patients receiving Zepzelca plus atezolizumab was twice as long as the atezolizumab arm, with a median maintenance treatment duration of 4.2 months versus 2.1 months, respectively. The combination was generally well tolerated, with no new safety signals identified.

We are also highly encouraged by results from the long-term phase 2 GEA trial of Zanidatamab, which showed a remarkable 36.5-month median overall survival after four years of follow-up in centrally confirmed HER2-positive first-line patients with GEA. These promising results provide additional confidence as we await the phase 3 Horizon GEA readout anticipated late in the fourth quarter of this year. An oral presentation of the safety and efficacy of Dirudavaprom from an integrated analysis showed promise in shrinking tumors in both adults and pediatric patients with an encouraging disease control rate. The results were in line with earlier studies, and side effects were generally mild. Now, I will turn the call over to Philip for a financial update. Philip?

Speaker 2

Thanks, Rob. I'll start on slide 19 with our top-line results. 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 second quarter of 2025, we generated $1.05 billion in total revenues. This represents an increase of 2% over last year's quarter and was driven by robust Xywav growth of 13%. As Renee mentioned, net patient adds were particularly strong, providing great momentum as we move into the second half of the year. Epidiolex growth moderated to 2% this quarter, driven by several factors, including year-over-year inventory dynamics in the U.S., as Renee mentioned earlier. Despite inventory dynamics, we continue to be pleased with the demand we're seeing for Epidiolex.

In total, our oncology products decreased 1% compared to the second quarter of 2024, as lower sales of Rylaze and Zepzelca were largely offset by higher sales of Zyhera, Defitelio, and Vyxeos. Looking forward, we remain optimistic and confident in the future of our oncology franchise and are ready to successfully execute on the rolling launch of Zyhera for biliary tract cancer in Europe and the potential near-term launches of Dirudavaprom in our current H3K27M mutant diffuse glioma and of Zepzelca in the first-line maintenance setting for small cell lung cancer. In addition, we look forward to the upcoming phase 3 first-line GEA readout for Zanidatamab. Adjusted net loss for the second quarter of this year was $505 million. This loss was entirely driven by the $905 million non-tax deductible acquired IPR&D charge from the Chimerics acquisition.

We continue to generate significant cash, recording $519 million of operating cash flow in the first half of the year. Even after the acquisition of Chimerics and payments to settle certain of the Xyrem antitrust claims we announced last quarter, our balance sheet is strong with $1.7 billion in cash and investments at quarter end. With that context, let's move to our revised 2025 financial guidance. You'll see on slide 20 that we've narrowed our 2025 revenue guidance by lowering the top end of the range, resulting in 4% growth at the midpoint. This change reflects our assessment halfway through the year that revenue is largely tracking to our expectations, with some potential upsides being less likely. Turning to slide 21, we've reduced both SG&A and R&D guidance ranges primarily because of our efforts to prioritize spend for our highest impact initiatives and to enhance operational efficiency.

In addition, we've incorporated refined estimates of ongoing Chimerics costs. You'll note that our revised SG&A and R&D guidance ranges do contemplate higher spending in the second half of the year than in the first half of the year. This uplift is primarily driven by the inclusion of Chimerics expenses for the full period, including a ramp of launch activities for Dirudavaprom. We're also increasing support for Zyhera and Zepzelca, making targeted investments behind Xywav and Epidiolex and/or accelerating activity across several Zanidatamab clinical trials. Looking at the second half of the year, I'd like to make a detailed comment that may help with your modeling, as well as a higher-level comment on how we're positioned. As you develop your expectations for sales of our U.S. oncology products, please note that we'll have 14 shipping weeks in the third quarter and 13 shipping weeks in the fourth quarter.

Year-on-year growth rates will be affected by the fact that we had the opposite pattern last year, with 13 shipping weeks in the third quarter and 14 shipping weeks in the fourth quarter. Hopefully, this information will minimize any surprises based on the calendar. Stepping up to a higher level, in the back half of the year, we have several commercial catalysts that position us for growth. Our disciplined approach to capital allocation ensures we're investing strategically in our high-priority R&D programs and in our lead commercial products. Our strong balance sheet and cash flow enable us to engage in value-creating corporate development as we did with Chimerics. We're confident this focused execution of our strategy can drive long-term growth, and we look forward to realizing the significant opportunities ahead. I'll now turn the call back to Bruce for closing remarks.

Speaker 0

I'll conclude our prepared remarks on slide 23. We remain well-positioned to deliver shareholder value as we head into the second half of 2025. We continue to focus on optimizing our commercial execution, advancing key development programs, and maintaining our commitment to patients who depend on our medicines. I'm pleased with the robust net patient adds exiting the quarter for Xywav, the only low-sodium oxybate, and continue to anticipate Epidiolex will reach blockbuster status this year. As our oncology portfolio overcomes near-term headwinds, we expect a return to growth driven by new opportunities. We look forward to our two upcoming PDUFA dates, one for Dirudavaprom this month and one for Zepzelca in October, as well as the top-line readout of the phase 3 Horizon GEA clinical trial expected late in the fourth quarter of 2025.

Again, I'd like to congratulate Renee and thank our talented employees for their dedication and commitment to innovating to transform the lives of patients and their families. That concludes our prepared remarks. I'd now like to turn the call over to the Operator to open the line for Q&A.

Speaker 1

Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press star one-one on your telephone and wait for your name to be announced. To withdraw your question, please press star one-one again. Also, we're only allowing one question. Please stand by while we compile the Q&A roster. Our first question comes from Mark Goodman at Leerink. Mark, your line is open. Our next question comes from Jason Gerberry at Bank of America. Your line is open.

Hey, guys. Thanks for taking my questions, and congrats, Renee and Bruce. It's been awesome working with you. Going to miss you. My question is, you know, what's driving the strength of Xywav and IH? Specifically, the patient ads look like they're sustainable and going up, and I'm just kind of curious if I can get your perspective on the sustainability of that rate of patient ads into next year. Thanks.

Speaker 0

Renee, you want to jump in on that? Renee, it looks like you're still on mute. While we're waiting for Renee to figure out how to get off mute unless somebody else can hear, I'll just say, Jason, it's been a pleasure working with everyone over the past many years. Jazz has been a public company since 2007. For a couple of you out there on the buy side and the sell side, I'd probably go back 30 years. It's been a real pleasure getting to know you all, and I will be watching Jazz's forward progress as all of you will under Renee's leadership. With that, Renee, over to you.

Speaker 6

Yeah, can you hear me now?

Speaker 0

Yes, we can.

Speaker 6

Okay. Great. Sorry, I'm not sure what happened there. Thanks, Jason. We're really pleased with the growth that we saw in the quarter with Xywav, both in narcolepsy and in idiopathic hypersomnia. In terms of IH, we do see that as being an area where we see the most opportunity for growth, as Xywav is the only FDA-approved therapy. In terms of what's driving the growth, we have seen some really strong execution across our field teams and our investments. Our consumer-targeted digital and media campaigns are performing really well. We have invested quite a bit in building disease awareness and patient education because this, of course, is an area where in the past, if you haven't had an approved therapy, there's not necessarily a large incentive to go through the process of getting diagnosed. I would say also our field nurse educator program is particularly helpful with IH patients.

When you think about starting oxybate therapy, there is greater persistence once you have titrated up to an efficacious dose. The field nurse educators assist with this, and in particular with this community of IH being less familiar with oxybate therapy as compared to narcolepsy, that's been another really helpful service that we've been providing to patients and is helping our persistence and overall growth.

Speaker 0

Yeah, thank you.

Speaker 1

Our next question comes from Jess Fye at J.P. Morgan.

Speaker 6

Hey, guys. Good afternoon. Thanks for taking my question, and congrats to Renee on the new role and to Bruce on retirement. I wanted to ask about Zanidatamab, for the phase 3 trial coming up. If I recall, Jazz's top-line updates have historically been more qualitative in nature with numbers to follow later. Is that how we should think about the Zanidatamab top line, or could there be potential for any numbers this time around? If the update is more qualitative, can we expect to hear comments on both Zanidatamab arms?

Speaker 0

Jess, I'll jump in first and then see if Rob wants to add anything. Typically, we've tried to give important top-line results in terms of have we hit or not a primary endpoint or certain pre-specified secondary endpoints if we think they're germane and important while preserving our ability to publish and present at major conferences by not sharing all the information. We've often tried to give qualitative commentary that helps people understand the clinical meaningfulness of results in other ways. We're not trying to leave people completely in the dark, but it's rare that we go all the way to full statistics. We're also, of course, often unblinding results and sharing them fairly quickly at the top line while continued analysis goes on at a very detailed level as we prepare for regulatory filings and otherwise. Rob, anything you want to add?

Speaker 4

I think that was great, Bruce. I would just say our recent experience with Zanidatamab is probably a good example where we not only set stat sig, but we commented on both endpoints, PFS and OS, and gave some color around it being clinically meaningful in practice.

Speaker 1

Our next question comes from David Asalem at Piper Sandler.

Thanks. I had a question on Zepzelca. I know you've talked about the competitive headwinds here. Your competitor on its call did cite growing traction of Tirelatumab in the community setting. I'm just wondering out loud, with that in mind, do you see continued headwinds for Zepzelca in second line? At what point do you start to see perhaps stabilization with the label expansion? When do you think we'll have better visibility into a return to growth for Zepzelca? Thank you.

Speaker 0

Yeah. Renee, you want to take that?

Speaker 6

Sure, I'm happy to jump in. Can you hear me?

Speaker 0

Yes.

Speaker 6

Okay. Perfect. Thanks for the question, David. Certainly, we have commented on a couple of different dynamics impacting our sales of Zepzelca, one being the increased competition in the second line of tiragolumab. These impacts were in line with our expectations. However, it is having an impact on our overall positioning in the second line. We have also said that we've seen increased adoption of IO in the treatment of first-line limited stage small cell lung cancer. This is the impact of the Adriatic regimen, and that's delaying progression of some of those first-line limited stage patients from the first line into the second line. We can see this trend in claims data. Importantly, we're really looking forward to the potential approval in first-line maintenance for extensive stage based on the Enforte study data that Rob Iannone was just mentioning. We have our PDUFA date on October 7.

We have already submitted for potential inclusion in the NCCN treatment guidelines. We do expect this data to be practice-changing, and we do expect, as we look at that first-line population, to have a larger group of patients. We have talked about the duration of therapy also being longer there. That's really what we're focused on.

Speaker 0

Thank you.

Speaker 1

Our next question comes from Andrea Flynn at Goldman Sachs.

Good afternoon. Thanks for taking the question. Maybe as a follow-up to a prior one, for Rob, when you think about the sustainability of Xywav's growth profile on the forward, is there anything you're looking to understand from the upcoming orexin data presentations at World Sleep to better inform how you think orexin agonists and oxybates will coexist in the rare hypersomnia space?

Speaker 4

Thanks for the question. Certainly, we've only seen limited data, and I am eager to see as much data as possible, not only in terms of daytime efficacy measurements, but the overall safety and tolerability profile. I am very, very interested in understanding the impact on nighttime sleep. As we know, alerting agents often can disrupt nighttime sleep, which is really the root cause of narcolepsy. Narcolepsy patients have substantially disrupted nighttime sleep. For example, on average, about 80 awakenings a night with not as much deep sleep or total sleep time. The impact on nighttime sleep, where Xywav has its main impact and results and benefits during the day, is going to be important. We continue to think about these two mechanisms as potentially being complementary.

Speaker 1

Our next question comes from Akash Tewari at Jefferies.

Hey, thanks so much. Rob, you mentioned that for the top-line press release for Horizon GEA, you could give commentary on whether the PFS would be clinically meaningful and practice-changing. Can you kind of prospectively identify what that would look like for Zanidatamab in that indication? Maybe, Renee, I had asked Bruce this maybe a year ago. When you think about core and non-core parts of Jazz, I think Bruce had alluded there could be parts of Jazz that are non-core to the business going forward. You guys have such an esoteric mix of products. How would you define what is core and non-core within the Jazz portfolio? Thank you.

Speaker 4

Yeah. Thanks for the question. I would say it's always hard to give a specific number to say if we observe this, we think it'll be practice-changing. This field certainly has evolved over the last 10 to 20 years, and you can look at examples of how clinical trials have resulted in change in practice, whether that be from the TOGA trial to establish Herceptin through the Jacob trial, and then more recently, KEYNOTE 811. KEYNOTE 811 had about a two-month median PFS difference and about a four-month overall survival difference. I think the benchmarks are out there. We're very encouraged by the two front-line phase 2 trials that have been conducted. One recently published at ASCO, Zani plus chemo, with a median overall survival of 36.5 months, very encouraging, but strong, strong response rates, duration of response in PFS as well.

Those data were very comparable to the other trial where tizolizumab was added, and you saw, in some respects, incrementally better results as well.

Speaker 6

Yeah. I'm happy to jump in on the second question, Akash. I appreciate that you are thinking about core and non-core parts of Jazz. I do think at times what people miss is at the core of our business, the vast majority of our products are essentially rare disease or orphan disease products. While on the surface, they may not always look like they fit together, the underlying capabilities that are required to identify patients, to be able to partner with, interact with patient advocacy groups, to understand patient needs, to be able to target and engage with physicians in some of the field execution capabilities, those are actually quite similar across a number of our products.

I would also say when you look at Jazz over time, there have been a number of businesses, products that we have decided to divest because they did not necessarily fit into the core business that we were looking to drive growth and where we felt we could invest to continue to bring forward. I would say Sunosi is a good example of that. Even though it was a product within sleep, it no longer fit the type of business model that we were focusing on going forward. As I'm stepping into the new role, I will be looking at where's the best place for us to be investing. As I mentioned, I do intend to spend time listening, talking to both internal and external parties to better inform the direction that we go forward.

We are in an excellent position today with roughly $4 billion of top-line revenue, healthy cash flows, and multiple products to be able to invest in, both on the commercial and pipeline front, as well as continued appetite for corporate and business development.

Speaker 1

Our next question comes from David Wang at Deutsche Bank.

Hi there. Congrats on the quarter-end. Thank you for taking my question. Maybe one on Epidiolex. I want to ask about what underlies the confidence there that that product will reach blockbuster status this year, and are there any potential headwinds that may be related to seasonality that could impede those growth expectations? On the oxybate franchise, could you just refresh us about potential entry of multi-source oxybate generics near term and how that might impact the business? Thank you.

Speaker 6

Sure. I'm happy to jump in on both of those. With respect to Epidiolex, this is a product that we do remain confident in in terms of reaching blockbuster status this year and ongoing growth. It's also a product that does tend to see seasonality that impacts inventory and, as a result, can impact our growth when you're comparing quarter over quarter. The second quarter is an excellent example of that. We saw strong underlying demand growth, but we also saw atypical inventory build last year. Typically, we see inventory build in the second half. It burns off in the first quarter, sometimes into the second quarter. Last year, we saw that inventory build start in the second quarter, which therefore, as a result, not seeing that same dynamic in the second quarter of this year means it negatively impacted our growth rate.

We do expect to see a gradual build of inventory in the second half of this year. The overall growth, when you look between 2024 and 2025, doesn't actually need to be very high in order to reach blockbuster status. Given the strong underlying demand that we see, we feel highly confident that we'll achieve that at a minimum. With respect to your second question.

Speaker 4

Yeah, timing of multi-source generics.

Speaker 6

Yes. Sorry. Thank you. With respect to the timing of multi-source generics, they have the ability to enter on December 31, 2024. Of course, HCNA has the ability, with notification to us, to enter at any time. They have had that ability over the last roughly year and a half, as well as the ability to extend the AG agreement through the end of 2027. If a generic enters onto the market at the end of this year, they will need to have their own REMS to be able to support their product. We continue, as a result, to really focus on the differentiation of Xywav as the only low-sodium oxybate on the market, as the number one treatment within narcolepsy, the number one branded treatment, as well as the only product available and approved for idiopathic hypersomnia.

I think, Phil, you wanted to jump in and add something as well?

Epidiolex real quick, just in terms of the growth that's required. As Renee mentioned, you know, we finished last year with $972 million in global revenue. Effectively, you need less than 3% growth to get past $1 billion. We did grow 5% in the first half of the year this year. As you'll see in the Q where we have some disclosures on volume growth for certain products, volume growth continued to be robust at 6%. Some of these inventory things will fluctuate from period to period. As Renee mentioned, we're really pleased with the underlying demand that we're seeing for the product.

Speaker 1

Our next question comes from Amy Fadia at Wells Fargo.

Good evening. Thanks for taking my question. Congratulations to Renee on your new role and to Bruce and your retirement. I'm sure you'll be missed. My question is a follow-up on the Zanidatamab GEA trial. Given that you've increased the enrollment of the study somewhere in early 2024, do you think you'll have data that'll be mature enough for you to have a look on OS, or would you need to wait for the next interim look there? What is the bar for showing a trend towards OS benefit? Is it simply a hazard ratio under 1 or something more specific? With regards to the disclosure that we can expect in the fourth quarter with regards to arm C, how much of an improvement would you need to see versus arm A or B to indicate that adding tizolizumab is sort of incremental for PD-L1 patients? Thank you.

Speaker 4

Thanks, Amy, for the questions. As a reminder, we have three planned overall survival analyses. The first is timed for when we do the one and final PFS analysis. It doesn't have the full maturity that we'll have, even at the second, but certainly the final. However, the additional time, as you pointed out, in getting to the PFS endpoint improves the power in OS relative to what we might have had a year ago. It improves our chances, so to speak. Your next question was, how much of a trend is needed on OS? I think it depends ultimately on the totality of the data. We certainly don't get into that kind of specific discussions with health authorities, et cetera. Depending on the magnitude of effect of PFS, I think it'll all be considered together. There's a fair amount of precedence in this space in terms of approvals.

Of course, the TOGA regimen Herceptin showed an overall survival benefit. Keytruda had an initial approval, accelerated approval on response rate, and then full approval on PFS before having mature OS data. I think there is a certain amount of precedent in this space to go by. Lastly, you asked the question of what is the incremental benefit that you need to observe in arm C versus B in order for that to be approvable. Again, I think it's a totality of the data question. Certainly, it needs to be contributing meaningfully, and the overall benefit risk needs to be favorable.

Speaker 1

As a reminder, for every person, make sure you limit your question to just one question. Our next question comes from Joseph Tone at TD Cowen.

Hi there. Good afternoon. Thank you for taking my question and adding congrats to both Renee and Bruce. Maybe when we talk about the frontline GEA data, this has been pushed a little bit. Even though it's in the current guidance, it sounds like it's going to be later in the fourth quarter, I guess. Can you talk a little bit about your confidence that the data will come this year? Also, maybe your confidence that the control arm, A, is performing similarly to prior studies? Maybe just a little bit of an attack on when would that subsequent OS analysis be? Thank you.

Speaker 4

Yeah, I would just say we remain blinded overall to the data. As we get further along in the study and more mature, the assessments around when maturity will come have greater precision. We have greater confidence in our projections around that, and that has led to a refinement there. Could you clarify again the last part of the question that you asked?

Yeah. I guess just the confidence that the control arm is performing similarly to prior studies. You indicated that there's several OS analyses, and the first one comes with a mature PFS. I guess when is the next one after the mature PFS? When would you expect that to be available?

Sure. This is an area that's, I would say, a disease setting that's been very, very well studied. If you look at TOGA, Jacob, and then KEYNOTE 811, the control arm has performed in a fairly narrow band. I think it's reasonable to expect in the modern era that the control arm would be similar to the KEYNOTE 811 results. We're blinded to the data, so we can't say for sure how the control arm is performing. I think that Herceptin and chemotherapy has performed pretty consistently across studies, which makes it easier for planning purposes. We haven't given details on exactly how much maturity we would have, for example, on the second interim analysis.

What we have said in the past is when we increased the sample size from approximately 700 to approximately 900, it allowed us to roughly maintain what had been the timing for and what had been planned for a final OS analysis while adding a later analysis to be the final and to be better powered.

Speaker 1

Our next question comes from Joan Lee at Truist Securities.

Hey, thanks for the updates and for taking our questions. You have a very strong momentum in the narcolepsy franchise, but Takeda is planning to submit an NDA for their orexin agonist for NT1, and Axiomm is also planning to submit an NDA for their NT1 narcoleptic drug in Q4. How much impact, if any, do you think that Takeda and Axiomm drug could have on your current momentum in the narcolepsy franchise, given the potential differences in the VA scheduling? Where are you with your orexin agonist 441? Thank you.

Speaker 0

Renee, you want to take the first part on the potential impact of product entry, and then Rob, any update on 441?

Speaker 6

Sure. Happy to do that. I would say I'll let Rob comment on some of the mechanisms, but we continue to believe in general that oxybates will be complementary to orexins. When we lay out the differentiation of Xywav, with both low-sodium being the only low-sodium oxybate on the market and flexible dosing, we see that HCPs and patients alike continue to choose the low-sodium based on the underlying cardiovascular conditions that often exist and the propensity to develop cardiovascular conditions on high-sodium oxybates. I would say also, when you think about other mechanisms, be it wake-promoting agents or stimulants, we simply have not seen a meaningful impact with any of those launches on our Xywav momentum. We would think of these as being largely complementary.

When you think about the studies that we ran for Xywav, we saw a large number of patients coming in on a background of wake-promoting agents and still improved meaningfully with Xywav. Rob?

Speaker 4

Yeah. I mean, I'd love to add that we have very, very extensive and robust data, not only with Xywav but in the oxybate field in general, and many, many years of patient experience showing that when administered at night, and of course, it's washed out by the time patients wake up in the morning, there's a very significant and clinically meaningful impact on nighttime sleep, improving key parameters like total sleep time, reducing awakenings after sleep onset dramatically, improving deep sleep, consolidating REM sleep. That improvement in what's essentially the underlying root cause of the daytime symptoms translates then into more wakefulness and less cataplexy during the day. Certainly, what we've seen of orexins is that they are potent daytime alerting agents. You know, what we haven't seen is orexins improving meaningfully nighttime sleep.

The little data that are in the literature shows some consolidation of REM sleep, but really no impact on total sleep or deep sleep. We haven't seen a lot of data around that first part of the night where residual exposure to orexins might actually be disrupting sleep. That's partly why we think that these mechanisms are likely to be complementary. I would mention that at APSS, we recently published more PSG data, both in narcolepsy and idiopathic hypersomnia, again establishing the value of Xywav for improving nighttime sleep. With regard to our own program, as we mentioned, we are already dosing in a small cohort of NT1 patients to evaluate whether JCP 441 could progress beyond this stage, depending on the therapeutic index that's observed. We continue to pursue a backup program that's in the preclinical space.

Speaker 1

Our next question comes from Ash Verma at UBS.

Hi. Thanks for taking my question. Congrats on your retirement, Bruce. I wanted to ask a bigger picture question on your journey. I know you've made pretty massive strides in terms of diversifying the business, but in terms of the stock, there was a significant outperformance from inception, but it's been gains bound for the last, let's say, 10+ years. From your perspective, what do you think drove that disconnect? Renee, any learnings you can take from this experience and how you think you can maximize the shareholder return as a CEO?

Speaker 0

Yeah. Ash, thanks for the question. I would say the diversification of our business has been important to have multiple growth drivers. Now, not only the strong continued performance of our sleep business, but the growth in Epidiolex now with its clearer long-term runway, as well as exciting developments in the oncology portfolio as we've continued to add new drugs and expand the opportunity for drugs we do have, with a lot of excitement in particular around Zanidatamab. A place we've begun to be more active again is corporate development. We've always said that's a part of our strategy. We had a bit of a pause after doing the larger GW transaction as we delevered, but that's a clear priority for us, as you saw with the Chimerics transaction earlier this year, which hopefully leads to a near-term launch and a really nice return for us.

We've been trying to make that strategic shift over a number of years. It's been quite dramatic, going from 75% of our revenues being dependent on one product, which is now a very, very small percentage of our revenues, to having these multiple drivers. I think we've set the company up well as a platform to continue to grow, and I'll let Renee talk about where we go from here.

Speaker 6

Yeah. Thanks, Bruce. I think at this point in time, it might be a bit premature, Ash, to go into a lot of detail. I'm thrilled to be stepping in where the company is today with respect to the strength of the balance sheet, the revenues we're generating. We have multiple approvals ahead, a very meaningful pipeline readout coming in GEA, and a workforce that is highly engaged and passionate about what we do. I do believe there is really meaningful value to unlock here, and I look forward to working with the team to be able to accomplish that. Stay tuned.

Speaker 1

Our next question comes from Sean Lemon at Morgan Stanley.

Hey, this is Mike Riad on for Sean. Thank you for taking our questions. I'd also like to extend our congratulations to both Bruce and to Renee. For JCP 441, is there a likelihood to get the phase 1B results this year in NT1, or is that more of a first half 2026 event? Thanks so much.

Speaker 4

We haven't given specific timing on that. All we've said is that it's a relatively small study. We think in, you know, 10 patients or fewer, we can get a read on the therapeutic index. It is an open-label trial, so patients are enrolling. As soon as we have meaningful information, you know, we'll provide an update.

Speaker 1

Our next question comes from Mohit Bansal at Wells Fargo.

Great. Thank you very much for taking my question. Congrats, Bruce, on the retirement and Renee, very well-deserved promotion. Looking forward to continue working with you. My question is regarding Caris and MSN. I think last quarter, you talked about island being important for Xywav. What about other products? Do you see any impact on products like Epidiolex and all as well? Given your portfolio of rare disease drugs, do you think the recent chatter around MSN impacting the Medicaid pricing could have an impact on these drugs as well? Thank you.

Speaker 2

Yeah, Mohit, thanks for the questions. Maybe starting with tariffs. As we had talked on prior call, we do have the opportunity to produce our oxybate products here in the U.S. with a supplier that has more than ample capacity that's available to us to serve all of our U.S. needs. We also have a U.S. CMO that does the drug product for Rylaze.

Speaker 1

Yes, Rylaze as well. I would say in terms of the exposure we've got to tariffs, similar to what we said in the past with steps we've taken to mitigate that risk, there really is no exposure to either the existing or some of the ones that are pretended to be coming here in the near future to our 2025 results. We have a decent amount of coverage for nearly all of our products in terms of U.S. inventory already here locally in the States to cover a decent portion of our 2026 needs as well. Beyond that, we'll continue to look for ways to go ahead and mitigate that exposure, which could include working with additional third parties here in the U.S. for other manufacturing. We'll continue to keep you updated there. On MFN, it really is obviously the sort of topic of the last few days here.

A lot still is unclear about scope, timeline, operational mechanisms of how the administration may pursue MFN drug pricing, what may happen legally in terms of challenges to proposals that could be coming. I'd say at this point, it is premature to speculate on what's going to happen specifically and therefore put some kind of quantification of our exposure. I would say we do have exposure because we do have U.S. government business and ex-U.S. prices are typically lower than U.S. prices. Some of the products that would have a larger exposure for us based on their proportion of government business would include, for example, Rylaze and Epidiolex. Much more to come here, I'm sure, in the coming weeks and months. We'll keep you appraised as we have something more specific to be able to say based on concrete proposals.

Speaker 9

Awesome. Thanks.

Speaker 0

Our next question comes from Gary Nachman at Raymond James.

Speaker 4

Thanks. Bruce, best of luck to you. And my congrats as well, Renee. On Dirudavaprom, what's your confidence level in the accelerated approval at the PDUFA on August 18th? Have your conversations been going with FDA if that's all been on track? I know you'll have a webcast after, but high level, how are you thinking about that opportunity and how quickly it could ramp up in that subset of glioma patients? Can you just roll this into the current oncology sales infrastructure? Thanks.

Speaker 2

Yeah, maybe in the interest of time, since we're getting short, I'll just say, Gary, you know, we've been in conversations with FDA, and we know what the PDUFA target action date is, and we hope to have an FDA decision very soon. Renee, maybe I'll let you comment a little bit on the opportunity. I'll just say we're really excited about the opportunity to bring this therapy to patients and think there's a real, nice opportunity to make a difference for a lot of patients.

Yeah, absolutely. Happy to make a few comments. First, we are incredibly excited about this potential approval and making this medicine available. This has been, I would say, a true labor of love for our colleagues at Chimerics, and we look forward to bringing it to market. We do believe the product will be predominantly administered in academic settings of excellence. We think largely a more concentrated call point. As a result, we are looking at a relatively small but dedicated group to be able to augment our internal footprint, ensure we have sufficient focus on the launch, but also do so in a highly concentrated way. I would say we're also excited about this patent portfolio that goes out well into the late 2030s, 2037, with the potential to receive patent term extension. We also believe this is a durable, long-lived product.

More to come, though, with respect to our launch meeting.

Speaker 0

Our last question comes from Mark Goodman at Leerink.

Speaker 6

Hi, good afternoon. Thank you for taking our question. This is Basma on for Mark. Could you please provide a quick color on the launch or on the BTC performance of the second half, the Zyhera in BTC in the second half of the year? We just have a quick question on Epidiolex. Can you remind us if you did collect cognitive data in the different DEs, such as LGS and DS and DRIV-A? That's it for us. Thank you.

Speaker 2

I think in light of the limited remaining time, we'll just answer the first question, which Renee, maybe we'll come to you on the BTC launch.

Sure. I would say keep in mind that BTC represents a very small patient population. As we've said, while this is very important for us to make this medicine available for patients, we do expect the revenue contribution to be modest. We don't provide guidance by product. I'm not going to give specific expectations for the second half, but I would say what we're hearing from HCPs is they're really pleased to have the product available. They're having a positive experience with the drug. For us, we're really looking forward to seeing the GEA data late in the fourth quarter.

Speaker 0

This concludes the question and answer session. I would now like to turn it back to Bruce Cozadd for closing remarks.

Speaker 2

All right. Thank you, operator. I'd like to close today's call by recognizing our Jazz colleagues for their efforts and thank our partners and shareholders for their continued confidence and support. As I said earlier in the call, it's been a pleasure working with many of you for a few years, a lot of years, a decade, two decades, or three decades, depending on who I'm talking to. You're in very good hands with the continuing Jazz team. Good afternoon, everyone.

Speaker 0

Thank you for your participation at today's conference. This does conclude the program. You may now disconnect.