Jazz Pharmaceuticals plc

Good afternoon, and thank you for attending the Jazz Pharmaceuticals second quarter 2023 financial results call. My name is Alyssa, and I will be your moderator for today's call. All lines will be muted during the presentation portion of the call with an opportunity for questions and answers at the end. I would now like to pass the call over to the Jazz Pharmaceuticals team. You may proceed.

Thank you, operator, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its second quarter 2023 financial results. The slide presentation accompanying this webcast is available on the investor's section of our website. Investors may also refer to the press release we issued earlier today, which is also posted to our website. On the call today are Bruce Kozad, Chairman and Chief Executive Officer, Renee Galah, Executive Vice President and Chief Financial Officer, Dan Swisher, President and Chief Operating Officer, and Rob Hunone, Executive Vice President, Global Head of R&D. Kim Sablich, Executive Vice President and General Manager, United States, will join the team for Q&A. 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 and commercialization milestones and goals, which involve risks and uncertainties that could cause actual events, performance, and results to differ materially from those contained in these forward-looking statements. We encourage you to review the statements contained in today's press release, in our slide deck, and in our latest SEC disclosure document, 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. Turning to slide three on this webcast will discuss non-GAAP financial measures, 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.

Thanks, Andrea. Good afternoon, everyone, and thank you for joining us today. I'll start on slide five. In the second quarter of 2023, we once again delivered strong commercial results, advanced our efforts to unlock the tremendous potential of our pipeline, and built on our record of driving operational excellence. In particular, our results in the second quarter highlight the durability and growth potential of our commercial portfolio, the capabilities and productivity of our R&D efforts, and our focus on operational excellence. We are pleased to report strong execution across our commercial portfolio with all three key growth drivers of our commercial business, SideWave, Epidiolex, and Rylase, achieving year-over-year double-digit growth. Zywave grew by 39% in the second quarter compared to the same period last year and is annualizing at well over a billion dollars in revenue. Zywave continues to be the OxyBait of choice and the only approved therapy for idiopathic hypersomnia. We expect our OxyBait franchise to contribute $2 billion of the $5 billion in total revenue component of Vision 2025 and are well positioned to reach this target. As a reminder, our 2023 neuroscience revenue guidance, which we are raising at the midpoint today, and Vision 2025, both account for the availability of high sodium oxibate authorized generics, or AGs, and branded fixed dose high sodium oxibate. Epidiolex growth remains strong, and we are confident in its potential to reach blockbuster status. We achieved double digit net sales growth in 2Q23 compared to the same period last year as we continue to drive prescriber growth across our global markets. Our launch in Europe is gaining momentum with additional international launches and indication expansions expected this year. In oncology, Rylase has continued to grow in the U.S., underpinned by strong demand and our increasing emphasis on the adolescent and young adult market. Moving to our pipeline, Given the level of productivity in our R&D organization, I'm going to call out just a few items. Rob will cover our R&D progress in more detail later in the call. Our pipeline continues to advance towards meaningful catalysts with the potential for as many as four late-stage data readouts through 2024, the first being JCP150 late this year, followed by Suvacaltamide and Xanidatamab and GEA next year, and top-line PFS for Zepzelka in combination with Ticentric in first-line extensive-stage small-cell lung cancer at the end of 2024 or early 2025. In addition to its strong commercial performance in the U.S., we are extremely pleased that we recently received a positive CHMP opinion on our marketing authorization application for JCP458, marketed as RILAs in the U.S., and expect European Commission approval later this year. Since we added Zany Datamab to our pipeline last year, it has continued to impress, and we're excited by its broad applicability, which we believe represents 2 billion plus in peak sales potential. Positive, pivotal data from our Phase IIb trial in biliary tract cancers, or BTC, were featured in an oral session at this year's ASCO conference and concurrently published in the Lancet Oncology These data were also selected for the best of ASCO meeting. Top-line data readout from the ongoing Phase III gastroesophageal adenocarcinoma, or GEA, trial is expected in 2024. I'm also pleased to report that we recently received IND clearance for JCP898, an engineered interferon alpha cytokine prodrug that is activated specifically within the tumor microenvironment where it can stimulate interferon alpha receptors on cancer-fighting immune effector cells. With this milestone achieved, we remain on track to initiate a phase one trial of JCP-898 later this year. On the operational side, we generated continued top and bottom line growth in the second quarter. Our commercial execution, coupled with our focus on operational excellence, has put us in a strong financial position. enabling us to execute a focused capital allocation strategy to invest in the products, pipeline programs, and corporate development opportunities with the highest potential to deliver sustainable growth and enhanced value. Given our financial strength and our current stock price, we have resumed share repurchases under our existing program, which Rene will expand upon shortly. Based on our performance in the first half of 2023, and expectations for the remainder of the year, we are raising our full year financial guidance for 2023. And longer term, we believe we are well positioned to achieve Vision 2025. Renee will provide additional commentary on our financials and guidance later in the call. Turning to slide six, we are excited about the progress we've achieved in the second quarter and believe it has substantially advanced us in all three areas of Vision 2025. and we are well-positioned to achieve these important milestones in our transformation to a high-growth global biopharma leader. I'll now turn the call over to Dan to review our commercial performance, after which Rob will share an update on our R&D progress, Renee will provide a financial overview, and then we'll open the call to Q&A. Dan?

Thanks, Bruce. I'm excited to provide an update on our commercial progress. Starting on slide 8, with neuroscience and OxyBait, we remain confident in the strength and durability of our OxyBait franchise as ZyWave continues to be the OxyBait of choice and the only approved therapy for IH. ZyWave revenues were $327 million for the second quarter of 2023, representing growth of 39% compared to the same period in 2022. I'll note this growth was against the backdrop of high-sodium oxibate competition entering the market in January of this year. In narcolepsy, our focus remains on educating patients and prescribers on the benefits of reducing sodium intake, and this message continues to resonate. In addition to health benefits of lower sodium, based on our discussions with healthcare professionals and experienced oxibate patients, dosing flexibility is a valued attribute of ThyWave. exiting the second quarter approximately 9,300 narcolepsy patients were taking ZyWave, and ZyWave continues to be the oxidative choice in the marketplace. In IH, we see continued growth of new prescribers with approximately 2,200 active patients taking ZyWave for treatment of IH exiting the second quarter. IH is a 24-hour sleep disorder. Despite sleeping a normal or longer-than-normal amount of time each night, People with IH may still experience debilitating symptoms during the day. ZyWave is the first and only treatment approved by FDA to treat the full condition of IH. We are focused on educating prescribers on the importance of proper diagnosis and identifying appropriate patients who can benefit from ZyWave therapy. And a survey of sleep specialists indicated that 70% anticipate increasing their prescribing in the next six months. With regard to the average number of patients on ZyWave exiting the quarter, there was an operational change in our specialty pharmacy which caused delays in getting refills on time for some ZyWave patients. This is being addressed, and importantly, overall second quarter ZyWave HCP and patient demand were in line with our expectations in prior quarters. As Renee will review in more detail, we have raised our neuroscience revenue guidance at the midpoint reflecting our continued confidence in the growth opportunity for ZyWave and the durability of Oxibate. Total revenues for the combined Oxibate business, including royalties from a high-sodium Oxibate AG, decreased 2% to $492 million in the second quarter, compared to the same period in 2022. There were approximately 16,200 total average active Jazz Oxibate patients second quarter, a decrease compared to the end of the first quarter, primarily reflecting the expected impact of xyrem as a result of the availability of a high-sodium oxidate AG. Our focus is on continuing to grow low-sodium xywave across both narcolepsy and IH, and we are pleased with xywave's growth across both indications, even as additional high-sodium oxidate competition is available for patients with narcolepsy. The continued growth of ZyWave is one of the factors that contributed to our increased 2023 neuroscience revenue guidance. And as Bruce mentioned, we are well positioned to achieve our vision 2025 target of $2 billion in revenue from our OxyBase franchise. Slide 9 highlights the compelling low sodium health benefits we are sharing with healthcare professionals and patients, as narcolepsy is a debilitating chronic condition We have focused on educational efforts around the lifelong burden of high sodium intake for narcolepsy patients who live with a two to three times higher risk than the general population of cardiovascular comorbidities, such as stroke and heart failure. Zywa is the only approved low-sodium oxidate, and the only oxidate without a labeled warning about high sodium intake has 92% less sodium than high-sodium oxidates. The American Heart Association recommends a maximum of 1,500 milligrams of sodium per day. While high-sodium AGs and branded oxidates have 1,100 to 1,640 milligrams of sodium, DiWave has only 100 to 140 milligrams, a reduction of 1,000 to 1,500 milligrams of sodium per day. To put this in perspective, it would take 12 years of treatment with Zywave to equal the sodium intake of one year of high-sodium-oxibate treatment. This has significant potential health benefits, including lower blood pressure and improved cardiovascular health. To add to the literature on sodium impact, we presented data at this year's American Academy of Neurology meeting that showed narcolepsy patients treated with high-sodium-oxibate at a higher risk of new onset hypertension diagnosis or antihypertensive medication initiation within 180 days of starting therapy when compared to a matched control group of narcolepsy patients not being treated with high sodium oxibate. In fact, the risk of those taking high sodium oxibate was approximately twice that of the control group. We believe these data highlight that sodium intake is a health concern for all narcolepsy patients and one that can have near-term consequences. FDA has recognized that the difference in sodium content between ZioWave and high-sodium oxidase, including Zyrum, AgZyrum, and Lumerize, is likely to be clinically meaningful in all patients with narcolepsy, and that ZioWave is safer in all such patients. Lumerize is a recently launched, branded, fixed-dose high-sodium oxidase that has the same sodium content as Zyrum. We believe that the majority of patients and healthcare providers will continue to prioritize long-term health when evaluating OxyBase therapy. With respect to competition from high sodium OxyBase authorized generics, or HEs, Amneal announced the launch of their HE in early July. Two additional companies, Lupin and Parr, also have rights to launch an HE product. At this time, Parr and Lupin have elected not to launch These three AG suppliers are each restricted to a low single-digit percentage of Xyron sales volume. As a reminder, earlier this year, ICMA launched a volume-unlimited AG. Jazz receives meaningful royalties on all high-sodium oxygate AGs. Moving to slide 10, we remain confident in the blockbuster potential of Epidiolex. With yet another quarter of double-digit year-over-year revenue growth, Net product sales increased 15% to $202 million in the second quarter compared to the same period in 2022, driven by underlying demand. We have seen increased penetration in the long-term care setting, driven by additional in-person engagement with physicians, and we have additional opportunities for growth. Turning to slide 11, we are focused on multiple opportunities to drive epidemics to blockbuster status. We continue to see a positive impact from our educational efforts focused on optimal dosing and caregiver-reported outcomes beyond seizure control from the BECOM survey, which further differentiates Epidiolex from other anti-seizure medicines. In particular, reports from the field indicate that the BECOM data has been very impactful with both HCPs and caregivers. The compelling clinical data regarding the use of Epidiolex in combination with Clobizam is using the agents individually continues to resonate. Our commercial team also has an enhanced focus on further penetration into the adult setting. We are also pleased our commercialization efforts outside the U.S. continue to gain momentum. Slide 12 illustrates our progress in expanding Epidiolex outside of the U.S. Epidiolex is now launched and reimbursed in 23 countries around the world, including all five key European markets. While it's early, We are very encouraged by initial uptake in these markets with favorable pricing and access. We anticipate additional reimbursement decisions and submissions through this year and next. Moving to our oncology franchise, beginning on slide 13, net product sales for Rylase were $102 million for the second quarter, a 39% increase year over year in our fourth consecutive quarter of growth. We continue to see strong demand for Rylase reflecting the significant unmet patient need for a high quality reliable supply of erwinia asparaginase for patients with acute lymphoblastic leukemia. Based on the availability of Rylate, healthcare professionals have indicated they are returning the best clinical practice in switching therapy at the first signs of hypersensitivity. We continue to receive positive feedback from healthcare providers about the adoption of the Monday, Wednesday, Friday dosing regimen. allows a dosing schedule that is more in line with preferred clinical practice. Brylase has been almost universally adopted in pediatric oncology protocols, and we are encouraged to see that there is increasing use of Brylase in the treatment of adolescents and young adults or the AYA market, which is an area of increased emphasis for us in 2023. Outside of the U.S., we recently received a positive CHNP opinion With the positive opinion granted, we anticipate EC approval of our MAA submission later this year. Regarding the market opportunity, I'll note that there is competition in many European markets. Jazz has consistently delivered a reliable, high-quality supply of this important therapy in the U.S., and we are excited for patients and healthcare providers in Europe to have the opportunity to complete their full course of asparaginase therapy. Turning to slide 14, We rapidly established Zepdelka as a treatment of choice in second line small cell lung cancer. That product sales increased 3% to $70 million in the second quarter compared to the same period in 2022. We have achieved significant penetration in the second line setting, but there remains significant unmet need for patients diagnosed with small cell lung cancer. with five-year overall survival rates of less than 10% and median overall survival of six to 24 months, depending on the stage of diagnosis. Given this prognosis, there is a further opportunity to both improve patient lives and drive growth through our pivotal phase three trial in first-line small cell lung cancer in combination with Ticentric. We expect top-line PFS data readout at the end of 2024 or early 2025. In the U.S., there are approximately 27,000 first-line small cell lung cancer patients treated annually. DepthELCA has the potential to increase the duration of response with these earlier stage patients. With that, I'll turn it over to Rob for an update on our pipeline and upcoming milestones. Rob?

Thanks, Ben. Starting on slide 16, we provided an overview of the key clinical programs in our diversified pipelines. We are excited about the advances we've made so far this year, with the potential for as many as four late-stage data readouts from 2023 and 2024, which include JZP150 in PTSD, subacaltimide in essential tremor, stanidatumab in GEA, and Cevcelca in combination with Dicentric in first-line small cell lung cancer. I'll discuss a few of our programs in more detail shortly, but I wanted to broadly highlight our progress across the pipeline before moving on. Starting with neuroscience, we expect top-line data from our Phase II trial of JCP150 and PCSD by the end of the year. For JCP441, our REXIN2 receptor agonist that has the potential to treat narcolepsy, IH, and other sleep disorders, We anticipate initial proof of concept and healthy volunteers later this year. In addition, we have ongoing trials for suvacaltamide in both central tremor or ET and Parkinson's disease tremor. The top line data from the ET trial expected in the first half of 2024. Moving to oncology, then a data map is a priority program for us. We aim to advance that a data map to the market as rapidly as possible with second-line BTC representing our first potential commercial indication. We are planning for a potentially accelerated approval of Xanadatamab in second-line BTC and have alignment with the FDA on a confirmatory trial in first-line metastatic BTC, where there remains unmet patient needs. We are also evaluating Xani in GEA, breast cancer, and other HER2-positive solid tumors. For Zipselka, we expect top-line PFF data readout at the end of 2024 or early 2025. Small-cell lung cancer patients have particularly poor outcomes, with a five-year overall survival rate of less than 10%. Currently, Zipselka is indicated to treat patients in the second-line setting, but we see a clear mechanistic rationale for Zipselka to potentially benefit more patients and increase the duration of response in the first line setting as maintenance therapy in combination with the standard of care. Beyond small cell lung cancer, we have elected to close our phase two basket trial based on limited responses and three solid tumor cohorts. We're analyzing the findings from that trial and continue to explore additional tumor types that may benefit from treatment with Zypselka. As Dan and Bruce mentioned earlier, we are very pleased to have received a positive CHMP opinion on JZP458, which is marketed as Rylase in the U.S., with Monday, Wednesday, Friday, and every 48-hour dosing regimens, as well as IV and IM administration. We anticipate EC approval later this year. Moving to slide 17, I'll expand on my earlier comments regarding XANA data map. Benadatumab is a novel bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparotopic binding. This unique design results in multiple mechanisms of action, including dual HER2 signal blockade, receptor clustering on the cell surface, leading to internalization via biparotopic binding, and potent immune effector functions, including antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity, leading to encouraging anti-tumor activity in patients. Then a data map has shown compelling activity across a broad range of HER2-positive tumors, and we've presented promising efficacy and early survival data at both ASCO and ASCO-GI this year. Additional data presentations are planned for later this year, including quality of life outcomes from the Horizon BTC01 Pivotal Study at the European Society of Medical Oncology Annual Congress. This slide speaks to our development strategy presenting, which is focused on four key areas. First, target areas with no approved HER2 agents. such as the significant unmet need, second-line HER2-positive BTC, as well as other solid tumors. Second, maximize the opportunity in TEA and other HER2-positive tumors where we believe Xamadetamab has the potential to be the HER2-targeted treatment of choice, supplanting current HER2-targeted agents. Compelling data has demonstrated that Xamadetamab has the potential to be a foundational treatment for patients with HER2-positive Third, we see substantial opportunity in settings where Xanadenumab could be used in combination with standard of care or other novel therapies, particularly in breast cancer and in earlier lines of treatment. Fourth, we plan to build upon the compelling activity we've seen across a broad range of HER2-positive tumors to address the patient need in additional tumor types. We believe this approach will allow us to deliver an important new therapeutic option to patients and maximize the value of Xanadatamab. On slide 18, I want to provide more insight into our excitement about the long-term potential of Xanadatamab, which we believe could go beyond addressing significant unmet need in BTC and GEA to include breast cancer as well as multiple additional cancers that overexpress HER2. With the potential to transform the current standard of care in multiple HER2-positive cancers, we are committed to rapidly advancing and expanding our development program. We believe that ZanaDataMap has the opportunity to be a differentiated, bispecific treatment of choice for HER2-positive cancers. We expect to enter the market first in second-line BTC, where physicians will gain important experience with ZanaDataMap. The approach is supported by recent compelling data presented at ASCO and previously treated HER2-positive BTC. We are pleased to share that we are planning for potential accelerated approvals on a data map in second-line BTC based on the Horizon BTC01 data and are working to rapidly bring this therapy to patients in critical need. We've shared the impressive second-line data with the FDA can have alignment on a confirmatory trial in first-line metastatic BTC, where there remains an important unmet patient E. We are continuing to work with FDA regarding timelines, and as our conversations progress, we will expect to be able to provide further updates. Following market entry in BTC, we expect to have a path to approval in first-line GEA for the supplemental BLA submission. which provides a more streamlined approval process compared to a full BLA. With the treatment landscape evolving following recent data readouts, we continue to strongly believe that a substantial opportunity remains to address the unmet patient need through first-line GEA, including the HER2-positive CDL1-negative patient population, where the standard of care remains trastuzumab plus chemotherapy. For patients who are PD-L1 positive, we continue to believe that Xanadatumab has the potential to be the HER2-targeted treatment of choice, while also combining with Bayesian Tizolizumab in order to treat those who are eligible to receive anti-PD-1 therapy, GEA. Further, there remains an opportunity to move into earlier stages of GEA, where we see the potential to help those patients prior to the metastatic setting in the neoadjuvant and adjuvant settings. GEA represents a significantly larger patient opportunity compared to BTC. And a prior approval in BTC may also accelerate adoption into GEA treatment guidelines and protocols. We look forward to additional data from the ongoing pivotal phase three GEA trial, Horizon GEA01, expected to read out in 2024, which may support U.S. and global regulatory submissions. Breast cancer also represents a considerable opportunity, supported by promising early data as monotherapy in multiple combinations and across lines of therapy. Based on the efficacy and safety seen in studies to date, we believe that a data map is well-suited for early stage disease including potential use of neoadjuvant and adjuvant therapy. Further, we believe there is potential to help patients previously treated with trastuzumab, duroxetan, or TDSD, or for those patients who are ineligible to receive treatment with TDSD. Sanodatumab has also shown promise in HER2-positive and hormone receptor-positive breast cancer as part of a novel combination, supporting this We have ongoing trials in neoadjuvant breast cancer and the opportunity to expand into both combination regimens and later lines of therapy in HER2-positive and HER2-HR-positive breast cancer. We're also evaluating Xanadatamab through multiple earlier stage trials in other tumor types where few HER2-targeted treatment options are available. Xanadatamab has shown clinical activity across a diverse set of HER2-positive indications, such as colorectal cancer, non-small cell lung cancer, and multiple other cancers where there remain few targeted treatment options available to patients. Turning to slide 19, I would like to highlight JZP150, our novel, highly selective fatty acid amide hydrolase, or FAW inhibitor. is currently in clinical development for the potential treatment of PTSD with phase two top line data expected later this year. PTSD is a psychiatric disorder that affects millions of people and patients frequently have uncontrolled symptoms that impact their ability to perform activities of daily living and function socially. Only two antidepressants have received approval from FDA the treatment of PTSD symptoms in the past 20 years. Current first-line pharmacological treatments for PTSD, such as selective serotonin reuptake inhibitors, mitigate some symptoms of PTSD but are not designed to address the core underlying problem, fear extinction learning and its consolidation. Response rates to existing pharmacological treatments rarely exceed 60%, and even fewer patients achieve clinical remission. We have been granted FDA fast track designation for JZP150, underscoring the significant unmet needs of PTSD patients. JZP150 is a once daily oral medication that has the potential to impact the pathophysiology and symptoms of PTSD. Data to date have demonstrated benefits with fear extinction, and stress response in healthy volunteers. Slide 20 shows the PTSD pathophysiology and JCP 150's mechanism of action and treatment rationale. PTSD can result from direct or indirect exposure to traumatic experiences and events. Individuals with PTSD have intense and disturbing thoughts and feelings related to their experience that persist long after their traumatic event. They may relive the event through flashbacks or nightmares and feel sadness, fear, anger, and detachment from other people. In PTSD, fear extinction deficits contribute to the persistence of traumatic memories. Interventions to promote fear extinction learning are a foundation of PTSD treatment. Preclinical and clinical data indicates that exposure to stress and anxiety is associated with activation of fatty acid amide hydrolytes, or PHA. In addition, a PHA has the potential to directly target pathophysiological processes of PTSD. PHA is the enzyme responsible for the degradation of anandamide. Anandamide is reduced in PTSD, and failure of anandamide to return to normal levels can result in a number of behavioral conditions underlying PTSD, including increased anxiety and impaired extinction processing of emotional memory. Inhibition of FAH results in an increase in anandamide. This has been shown to reduce anxiety, improve fear extinction and recall, and improve sleep architecture and self-reported sleep quality. JZP150 is a potent, highly selective, an irreversible inhibitor of PHA designed to address the underlying cause of PTSD. Moving to slide 21, we have outlined the design of the Phase II PTSD trial. The primary endpoint of the trial is change in total symptom severity score using the clinician-administered PTSD scale, or CAS5, from baseline to the end of treatment. CAPS-5 is a structured 30-item clinical interview. It is a validated instrument considered the standard for diagnosing and assessing patients with PTSD and is an endpoint that has been determined to be appropriate for regulatory purposes. Beyond PTSD diagnosis, it also allows physicians to evaluate the severity of symptoms and impact on social and occupational functions. The trial has several secondary endpoints, including changes in scores on clinical global impressions of severity and the patient global impression of severity scales, from baseline to the end of treatment. The ongoing trial is enrolling approximately 270 patients and assessing two doses of JZP150 compared to placebo, which we believe adequately powers the trial to assess whether JZP150 is clinically meaningful in this patient population. We expect top line data by the end of this year. We are excited about the potential of JZP150 and look forward to updating you on our progress. Turning to slide 22, we are pleased to recently receive IND clearance for JZP898 and expect to initiate a phase one trial later this year. KCP-898 is an engineered interferon-alpha cytokine prodrug that is activated specifically within the tumor microenvironment where it can stimulate interferon-alpha receptors on cancer-fighting immune effector cells. High-dose interferon-alpha therapy is approved in multiple tumor types but is used sparingly based on its toxicity profile. Systemic delivery of cytokines can cause serious toxicities in peripheral tissues. leads to poor clinical outcomes given ineffective anti-tumor immune activation and unmanageable toxicity in patients. JCP898 is a conditionally activated interferon alpha, which is selectively activated in the tumor microenvironment. Through this approach, biologically relevant exposures are coupled with optimal cytokine potency while limiting toxicity in other tissues. We are excited to bring this novel molecule into the clinic later this year. Overall, our R&D team continues to advance multiple programs from our neurosciences and oncology pipelines, and we're looking forward to multiple near-term data readouts. Now I will turn over the call to Renee for a financial update. Renee?

Thanks, Rob. I'll start with our top and bottom line results on slide 24. As a reminder, our full financial results are available in our press release in 10Q. In the second quarter of 2023, we achieved $957 million in total revenues. This was driven by growth of our key products in both neuroscience and oncology, including another quarter of double-digit growth of ZyWave, Epidiolex, and Rylase compared to 2Q22. We're particularly pleased with the continued trajectory of Zyways, even with competition since the beginning of the year. Coupled with the continued Epidiolex momentum and strong growth for Rylase, we saw total revenue increase 3% compared to 2Q22. Our disciplined capital allocation and focus on operational excellence drove adjusted net income of $325 million growth of 6% compared to the same quarter in 2022. We continue to generate significant cash from our business, recording approximately $617 million of cash from operations in the first half of 2023, an increase of more than $100 million compared to the same period in 2022. Our strong overall financial position means we have significant flexibility to invest in priority commercial and R&D programs, as well as corporate development opportunities. Corporate development is a core component of Vision 2025, and we remain active in exploring opportunities to expand our commercial portfolio and pipeline. Turning to slide 25, We are updating our total 2023 revenue guidance to a range of $3.725 to $3.875 billion, reflecting a $25 million increase at the midpoint. This update is underpinned by an increase of $20 million at the midpoint of our neuroscience revenue guidance. Our increased 2023 neuroscience revenue guidance incorporates our continued confidence in the durability of our Oxibate franchise, in part based on the performance and growth of Zywave during the first half of the year, a time period in which we saw the introduction of high-sodium Oxibate competition. With regard to high-sodium authorized generics, we expect our royalties from HICMA, which is the only volume-unlimited authorized generic, to be significantly higher in the second half of 2023 relative to the first half. During the second half of 2023, the royalty rate from HICMA to JAS becomes fixed at a rate where we and HICMA both have substantial economics. We also receive royalties on other high sodium oxidate AGs, all of which are restricted to a low single digit percentage of diurem sales volume. As Dan noted earlier, Currently, only one additional AG has been launched. Our 2023 oncology guidance remains unchanged and reflects expectations of continued double digit growth for this franchise led by Riley's with a revenue range of 950 million to 1.05 billion and a midpoint of a billion dollars. Continuing to slide 26, Our capital allocation strategy includes investment in commercial brands to drive top-line growth, in our pipeline to drive long-term growth, and in corporate development where we remain actively engaged in assessing opportunities and which remains an important pillar of our growth strategy. We are maintaining our prior non-GAAP SG&A and R&D guidance for 2023. Consistent with our capital allocation strategy, Our enhanced investment in R&D is a direct result of our success in diversifying and advancing our pipeline, as well as prioritizing those programs that we believe will have the biggest impact for patients while delivering value and contributing to our growth. We believe there is tremendous unrecognized value potential in our stock, And therefore, supported by our strong cash flows and aligned to our strategic and disciplined approach to capital allocation, we have resumed share repurchases under our existing repurchase program. In the second quarter, we completed approximately $100 million of share repurchases. As of the end of the second quarter, approximately $336 million remained available for share repurchases under our current plan. Importantly, given our strong overall financial position, we are able to repurchase shares without compromising our ability to execute business development opportunities and invest in our innovative R&D program. On the bottom line, we expect to continue to deliver strong adjusted net income, or ANI, and have increased our non-GAAP ANI guidance to $1.29 to $1.34 billion, which implies a 41% year-over-year ANI growth at the midpoint. I would also like to highlight we raised our non-GAAP adjusted EPS guidance to a range of $18.15 to $19, an increase of $1.20 at the midpoint, primarily driven by our increased revenue and ANI outlook as well as reductions in our fully diluted shares outstanding. The decrease to our weighted average ordinary share guidance relates to both our share repurchase and to our recent irrevocable election to settle in cash the principal of our $575 million exchangeable senior notes due in 2024, thereby limiting potential dilution from these instruments. With our strategic investments, expanding product portfolio, R&D progress, and focus on operational excellence, we believe we are well positioned to achieve Vision 2025 and deliver further diversification, sustainable growth, and enhanced value to patients and shareholders. I'd now like to turn the call back to Bruce.

Thanks, Renee. I'll conclude our prepared remarks on slide 28. The first half of 2023 has been driven by focused execution and strong commercial results, evidenced by the durability of our Oxibate franchise, continued growth of Epidiolex, and strength in Riley's sales. We continue to advance our pipeline and invest in long-term growth, and we have as many as four late-stage data readouts through 2024 that have the potential to further diversify and transform our business. Our latest pipeline additions, any data map, is approaching several near-term clinical and regulatory milestones. Given its applicability across multiple tumor types and lines of therapy, we believe ZANI DataMap has $2 billion-plus in peak sales potential. We also remain focused on strategic capital allocation. With our strong cash flow, balance sheet, and margins, we have the financial flexibility to make significant investments across commercial, pipeline, and corporate development to drive sustainable growth and enhanced value. That concludes our prepared remarks. I'd now like to turn the call over to the operator to open the line for Q&A.

We will now begin the Q&A session. If you would like to queue for a question, press star 1 on your telephone keypad. To withdraw a question, press star 2. Once again, to ask a question, please dial star 1. If you are using a speakerphone, please pick up your handset before asking your question. We do ask that you please limit yourself to one question. We will pause here briefly as questions register. The first question comes from the line of Jason Gerberry with Bank of America. Your line is now open.

Hey, guys. Thanks for taking my questions. Mine is on the Phase III ZANI GEA study that's going to read out first half next year. Can you help frame what sort of data we can expect on the primary efficacy measures, the PFS, the OS? Is this a first interim? I'm just wondering if PFS and OS will be mature or if the focus really is on ORR in this data cut. Thanks.

Yeah, thanks, Jason. Rob, maybe I'll throw that one to you.

Just to clarify, what we said previously was in 2024. We didn't specify exactly when. And in that, we are referring to PFS as the initial readout. Does that clarify your question? Yeah.

The next question comes from the line of Joseph Thorne with TD Cowan. Your line is now open.

Hi there. Good afternoon, and thank you for taking my question. Maybe one on the upcoming PTSD readout. Maybe what's a clinically meaningful benefit on that cap scale? And when you talk about the type of patient enrolled, are these On concomitant SSRI or the SSRI treatment failures, can you just put that into context a little bit for us? That would be great. Thank you.

Yeah, go ahead, Rob.

Sure. So, we haven't said specifically, you know, what treatment effect that we've powered to, but you could draw some of your own inferences by looking at the sample size, et cetera, that's listed on. And you'll note that it's a placebo-controlled trial with two dose levels, yielding the total sample size. Patients are allowed other concomitant medications.

Thank you. The next question comes from the line of Mark Goodman with LeRinc Partners. Your line is now open.

Yes, hi. Could you please give us a little more color on the comment that you made regarding the operational issues with the specialty pharmacy and the Oxivate franchise and just give us a sense of how much you think it may have impacted patients in the quarter or whatever you think it may have impacted or is it impacting anything in the third quarter? Thank you.

Yeah, thanks for the question, Mark. Kim, you want to take that?

Sure, I'd be happy to. So let me start out by saying that, you know, we continue to be very confident in the strength and durability of our OxyBait franchise as low-sodium ZioAid continues to be the OxyBait of choice and the only approved therapy for IH. You know, the decrease in total average active JAS OxyBait patients this quarter primarily, you know, reflects the expected impact to Zirum as a result. of ZyWave adoption and the availability of AG Zyrum. In terms of ZyWave and the average number of patients on ZyWave exiting the quarter, there was what we're calling an operational change at our specialty pharmacy, which unfortunately caused a delay in some ZyWave patients getting their refills on time. So this has been addressed and importantly, I think to understand is that the overall 2Q ZyWave HCP and patient demand, the overall market demand for ZyWave was in line with our expectations and with what we saw in prior quarters. So this really was an issue at the pharmacy that affected some patients getting refills, not the overall demand for ZyWave. The benefits of reducing sodium intake in the market continue to resonate with our customers We're very confident in the growth opportunity for Zywave and the durability of the franchise. And, you know, while we expect Zyrem to continue to decline in line with the Zywave and AG adoption, as you heard, we've raised our full year 2023 financial guidance and increased our neuroscience revenue guidance at the midpoint. So, you know, overall, our increased neuroscience revenue guidance, you know, accounts for the performance and growth of Zywave during the first half of the year. in a time period in which we saw the introduction of high-sodium oxibate competition. So, you know, our focus remains on continuing to grow the low-sodium ZyWave, which is already, as you saw, annualizing at well over a billion dollars, and we remain very confident in the durability of the business.

Thank you. The next question comes from the line of Akash Tewari with Jefferies. Your line is now open.

Hey, thanks so much. So can you walk me through your confidence on the 2 billion sodium oxidate number for your long-term guidance? Let's say you continue to add about 250 IH patients a quarter until 25. That kind of implies IH will contribute about 600 million in sales by 2025. That means that your Narcolepsy franchise, which is about 1.7 billion today, only declines to about 1.4 for you to hit that 2 billion watermark. How do you achieve that with generic DenaVita launching? Like, what are we missing here? Also, I think you've previously mentioned the majority of the erosion impact for the sodium oxibate franchise will occur in 2023. Is that still the case today, given your advice and your advice? Thanks so much.

Yeah, Kosh, thanks for the question. You know, we outlined our confidence that oxibate business at Jazz would contribute about $2 billion toward Vision 2025 at the beginning of last year, at the beginning of 2022. Obviously, we reiterated that coming into 23, and we've now actually increased our short-term guidance in 23. As a reminder, what we meant by that $2 billion was the combined revenues from ZyWave, both in narcolepsy and in idiopathic hypersomnia, continued brand Xyrem sales, and our royalties on any AGs that come to market through our system. and we continue to feel confident in that. You didn't specifically mention the royalties in your analysis. I'll remind you that the contribution from those royalties is expected to be significantly higher in the second half of 2023 relative to the first half, and that the royalty structure we've disclosed from the HCMA relationship will actually reset up again in 2024. It's the combination of all those things that get us to the durability. Our big focus, as Kim explained, is on growing ZyWave. This is the longer, healthier choice for patients, given the benefits of low sodium in this chronic treatment. And we'd like to see more and more patients get the benefit of ZyWave moving forward.

Thank you. The next question comes from the line of David Amselem with Piper Sandler. Your line is now open.

Hey, thanks. So I wanted to come back to the Vision 2025 targets, particularly the $5 billion top line. It seems like the street in the broader investor community is not quite there regarding the $5 billion target. Just can you articulate what you think we're all missing? Is it something surrounding epidiolex? Is it Xanadatomab, for instance, is GEA, or biliary tract cancer, or both in that 2025 number? Just help us understand why there seems to be daylights. between that target and what folks are modeling for 2025. Thanks.

Yeah, well, let's review where we are toward Vision 2025. Again, we rolled this out at the beginning of 2022. We're six quarters in to a four-year period. We're feeling very good about the performance of our business overall. both relative to our guidance for 2023, which has now been raised on both the top and the bottom line, and our vision 2025. I just spoke about Oxibate and the durability of that franchise and the positive progress we're seeing with ZyWave. But let me remind you that half of our business today is already coming from Epidiolex and oncology. We're seeing double-digit growth in our three lead assets, Zywave, Epidiolex, and Riley's, which together are accounting for about 66% of our revenues. And when you look at the Oxibate piece, you know, Zyrem is now less than half of that piece of our business. So we've got growth coming in all of our key franchises, which we estimated would contribute in 2025 approximately $4.5 billion in aggregate. We left a placeholder in Vision 2025 intentionally. for our ongoing corporate development activities and said that products that were not part of our portfolio when we started Vision 2025 could contribute that last half a billion dollars. Zany Datamap may well contribute to that. We're not saying it's going to contribute all of the $500 million to be clear, but that was something added to the portfolio after we began this process. And we remain very interested in continuing to to access new commercial products and pipeline products through our corporate development efforts moving forward. Our financial position is strong. If you look at our cash investments, about $1.4 billion. You look at our cash flow in the first half of the year, approaching $620 million. Our leverage is down. So we feel like we're well-positioned to continue to bring in new assets, as we have over the company's history. If you go back any two- to three-year period, period in our history, you'll generally see us do a significant transaction. And we thought it was unfair to assume that we would suddenly stop doing transactions, particularly given our successful launches of a number of products in a row here and our strong financial position.

Thank you. The next question comes from the line of Ami Sadia with Needham. Your line is now open.

Hi, good evening. Thanks for taking my question. Perhaps continuing on the vein of the placeholder for corporate development, can you talk about your level of confidence in being able to hit a majority of that $500 million through some sort of business development? And where are your thoughts at currently in terms of alternative options in terms of use of capital, would you consider buying back more shares? Should you not be in a position to execute on such a deal? Thank you.

Yeah, thanks, Ami. Renee, can you jump in on this one?

Sure, I'm happy to. So, you know, Ami, we've talked quite a bit about our strategic and disciplined approach to capital allocation, and our priority first and foremost is investing in growth. So we're investing behind our commercial launches and growth programs. We're investing behind the pipeline, and we expect to continue to invest in corporate development. As Bruce mentioned previously, it has been an important pillar of growth for us, and we expect that to continue to be the case In addition, we also look at opportunities in terms of managing the balance sheet strategically. Bruce also mentioned we delivered pretty quickly, so we're in a great position today to be opportunistic in terms of additional investment for the balance sheet. And we did take the opportunity, just given what we view as immense untapped value right now within the stock, we did take the opportunity to to recommence share repurchases in the second quarter, and we think that was the right thing to do. In terms of future repurchases, we'll continue to look carefully at the opportunities set in front of us, prioritizing growth. And then specific to the $500 million placeholder, as you've heard on the call today, we're really excited about the opportunity for Zany Datamab. We think that's going to be an important program and eventually product for us and for patients we don't expect that to cover a large majority of the 500 million but it's certainly we certainly expect that to contribute and then beyond that we're quite active from a corporate development perspective as you've heard me say previously we're not going to overpay just to be able to meet this growth objective we also don't think that we'll need to we do think there are opportunities out there both within neuroscience and oncology, but also within the rare and orphan segment more broadly. As you know, the vast majority of our commercial products currently do fall within that category and we think there are applicable learnings in terms of, you know, working directly with patient groups and serving the needs of patients or underlying infrastructure. that those learnings can be shared both from our existing experience to other rare and orphaned conditions. So today, we feel quite confident in our ability to transact. We're well capitalized to be able to do so, as Bruce mentioned previously, and we think we've established a great track record as a partner of choice to be able to do so as well.

Thank you. Our next question comes from the line of Gregory Renza with RBC Capital Markets. Your line is now open.

Great. Good afternoon, Bruce and team. Congrats on the quarter. Thanks for taking my question. Bruce, maybe just a little bit on Epidiolex and just with respect to Dan's comments on the driver for potential continued growth. Just curious if you can comment a bit on any particular areas or drivers that kind of outsize and help to propel the growth that you're expecting. Certainly last quarter, first quarter, a little seasonality and seeing the momentum that you're speaking about now. Just curious how you see that playing out in the near term. Thank you very much.

Yeah, Greg, thanks for the question. Dan, you want to take up the dialects?

Yeah, thanks, Bruce. So with Epidiolex, you know, there's another quarter of double-digit growth with 15%, Greg. So really pleased to see, you know, the continued initiative that we outlined on the call. Continued face-to-face interactions, very important in the treatment centers, getting to more offices, more prescribers. You know, we've been enhancing our focus on the adult setting. In particular, in the U.S., we've gone after long-term care settings and seen increasing penetration there. You know, we've also been educating HCPs about the benefits of Epidocs beyond seizure control, and that was, you know, highlighted in the BECOM data, which was presented at the end of last year, which talks about, you know, cognitive and behavioral benefits. And, you know, we look forward to continuing to lean into that area, both with caregiver surveys and even interventional studies. And so we've got a real commitment to you know, continuing to generate data both within the indications and kind of outside those indications. You know, outside the U.S., the launches continue to go well. We're at 23 countries globally. We've had six positive pricing reimbursement decisions to date in the U.S. Sorry, outside the U.S. And importantly, we've got a phase three study on what we think could be, you know, a very significant market for us with epidemics in Japan. And so that's enrolling nicely, and we look forward to providing updates in the coming quarters.

Thank you. The next question comes from the line of Annabelle Samimi with Stiefel. Your line is now open.

Hi, just a couple more on Epidiolex. So you mentioned a couple of times now expanded indications. The only indication we know of that you're working on is the EMAS indication. Are there others that we don't know about that you plan on expanding into? And also with the EU launch, we now have 23 countries approved, I guess, five in the major EU countries, but are all those countries on board? Should we now see a significant expansion in Epidiolex-XUS? Thanks.

Rob, would you like to talk a little bit about some of the additional data we're generating with Epidiolex? And then maybe, Kim, you could talk a little bit about the potential for broader use of the product over time.

Yeah, so you're right that we're evaluating EMOS, and the objective there is to generate data in yet another seizure type, adding to the three indications we have. really trying to demonstrate that Epidiolex is broadly active across different seizure types, regardless of the underlying etiology. We also continue to provide evidence around the indications we have, both in terms of anti-seizure effectiveness, but also in terms of other potential benefits of Epidiolex. And you heard Dan refer to the caretaker survey, and we continue to support and and do studies along those lines as well.

Yeah, sure, Rob. So I'll say that we've had, you know, very nice growth in the three indicated populations as well as growth over time in the base of prescribers that are utilizing Epidiolex. And, you know, what we see traditionally as our customers get more and more experience with the product, usually starting in the three indications they see what it can do for their patients in terms of seizure control and now you know beyond seizure control that frankly they've been hearing about from caregivers since day one of the launch and this really gives them the confidence to start using it more broadly across the spectrum of various seizure types and so forth so we're clearly not promoting it outside that, but this is what we hear from the providers once they get the experience. They see the efficacy, they do start to utilize it earlier and more broadly across their patient population. And really the data, as we've talked about, that we've been sharing to really increase the efficacy perception of the product, the Clobizam combination data in and of itself, gets them to stop and think about, why am I reserving this for certain patient types? Most of my patients are on Clobizam. Most of them could still benefit from additional seizure control or beyond seizure benefits. And it really gets them to start thinking about, I should be using this more and more and more of these patients that are taking Clobizam.

Thank you. Our next question comes from the line of Jeff Hung with Morgan Stanley. Your line is now open.

Thanks for taking my question. For RILAs, you talked about focusing on adolescents and young adults. Can you talk a little bit more about how that's going and how much of that opportunity remains to be addressed? Yeah, Kim?

Sure, I'd love to. I love talking about RILAs. you know, what we've really seen with Rylase is just lots of excitement in general. And I think as we told you early on, it didn't take very long for healthcare providers to have confidence in the supply and to return to, you know, best clinical practice in terms of switching patients at the first signs of hypersensitivity. At this point in the pediatric market, It's been added almost universally to the protocols in that setting. So at the beginning of this year, we did tell you that we were looking to start trying to expand the adolescent and young adult market. There was quite a bit of usage, a fair amount of usage of the products in adolescents and young adults that were being treated in the pediatric center per pediatric protocol, but the adult centers were less educated, familiar, and experienced with using Rylase in this setting. And so we've gone out there this year. We have now spent two quarters educating them on the product about the importance of switching as quickly as possible when they see a hypersensitivity reaction. And we see nice orders coming through and a nice growth rate happening in this setting. So we don't think we're done. We haven't gotten all of these centers set to start using it. Some of them are still dabbling. So there definitely is, you know, some more growth to be had there. And I think it's important to remember that in the adult setting, you know, because this is a weight-based product, the average dose, you know, is higher than in the pediatric center. So each adult patient is worth more. So, you know, we're really pleased with Riley's at this date, but we think there's a little bit more room to grow here in the U.S. and then, of course, you know, ex-U.S.

Thank you. Our next question comes from the line of Balaji Prasad with Barclays. Your line is now open.

Good afternoon. This is Xiao Ang for Balaji. Thanks for taking our question. Just a quick one on your OX2R program. On the data for TAK994 that was recently published on New England Journal of Medicine and the factor for liver toxicity for TAK994 was the impact of reactive metabolics. So Takeda also mentioned that TAK861 and TAK994 do have the overlapping antibiotic pathways. So do you think JZP441 is well differentiated with TAK994 to avoid this issue? Thanks.

Rob?

Yeah, thank you for the question. So the liver toxicity associated with 994 was known at the time that we entered into the partnership with Sumitomo. And we focused on chemical series that we thought were distinct enough such that that wouldn't, that risk of liver toxicity wouldn't be carried over. And so we do think that our molecule is substantially differentiated from the chemical series that you referred to.

Thank you. The next question comes from the line of Mohit Bansal with Wells Fargo. Your line is now open.

Great, thank you for taking my question. And congrats on all the progress. So maybe one question regarding the authorized generics of CYRAM. Do you think they will have any impact on IH market as well? Because in our talks with doctors, they think that they can prescribe it. as long as peers cover it. Peers would probably cover it. So do you see this as a threat? Because doctors could use it off-label. Thank you.

Yeah, well, I'll remind you that Xyrem did not do a comprehensive clinical program in the way that ZyWave has. In IH, there's slightly different dosing information in the label. And while you're right that physicians can prescribe the product, that does not always mean that that product will be successfully reimbursed. Kim, any comments you want to make on the marketplace?

Yeah, sure. So, yeah, we've seen traditionally that ACPs have had trouble getting coverage, you know, for oxibate, for idiopathic hypersomnia because payers restricted it. With the introduction of Zyway for idiopathic hypersomnia, we have achieved nice coverage as we do with narcolepsy of 90% of commercial lives. Having coverage, there usually is utilization management criteria in place there and certainly heavier utilization management criteria around non-indicated products. So we feel confident that while a small portion of healthcare plans may cover high sodium oxibates, you know, in particular the AG for idiopathic hypersomnia. Most of them are following the FDA-approved label, you know, and ZyWave is the only FDA-approved treatment for idiopathic hypersomnia.

And Rob, maybe you could just expand a little bit on that slightly different dosing information.

Yeah, Bruce, just specifically with regard to narcolepsy or IH?

I meant IH, but you can talk about dosing flexibility generally.

Sure. So starting with IH then, the clinical trial allowed for an initial dose of up to six grams. And at the time it was designed that way because there was some uncertainty around whether IH patients would wake up. to take that second dose. What we found in the clinical trials that with initiation of ZyWave, patients with IH improved substantially. And in fact, we're able to go ahead and take the second dose. And overall, that was the more common dosing regimen, even though in the trial, and we find that to be the case in clinical practice as well. Along those lines for narcolepsy, as you know, DiWave also has dosing flexibility to allow for uneven doses, and we find that patients really do prefer this. Oftentimes, schedules are different from one patient to another, but even within a patient, schedules may be different day to day, weekdays, weekends, depending on family obligations, and they like the flexibility of uneven doses potentially.

Thank you. The next question comes from the line of June Lee with Truist Securities. Your line is now open.

Hi, congrats on the quarter and thanks for taking our questions. How do you quantify the tradeoff between having a once a night drug with high sodium versus twice a night drug with no sodium? Isn't having to wake up in the middle of the night also unhealthy? And as a quick follow-up, do you have any views on ribococaine currently in phase 3, 4, or for narcolepsy with data expected in the fourth quarter? Thank you.

Yeah, Rob, maybe I could have you jump in a little bit on the nighttime impact of oxibate therapy.

Yes, happy to, Bruce. So we know that narcolepsy patients have significantly disrupted their nighttime sleep. We also know that oxibates have a very big impact in improving the architecture of nighttime sleep, and we think that's why, for a short-acting drug, patients then have substantial improvement in daytime symptoms like cataplexy or excessive daytime sleepiness. When you look across studies of oxibates, whether that be a fixed-dose high-sodium version or or immediate release oxybate, there is improvement. It's very comparable. There's no evidence that a fixed-dose regimen improves the supplement nighttime sleep to a greater extent. Patients typically do not normalize their sleep, and there's really no evidence that waking to take a second administration impacts one way or another.

And then Rob, I think there was a question on Roboxetine at the end of the question as well.

And sorry, could you just repeat that for me then?

I think the question was any thoughts on data on Roboxetine? I mean, I'll just jump in and say historically we, in our conversations with KOLs, we've not found that there's as much interest in that as other drugs available or in development. You know, this has been available in certain markets for a long time in treatment of other diseases, but we haven't heard of a huge success in this patient population in the U.S.

Sure, okay. Thanks for clarifying that, Bruce, and I would just say that Our focus with ZyWave is a nighttime administration to address the underlying cause of disrupted nighttime sleep, which has profound effects in daytime symptoms. Voxetine is, you know, one of several drugs that's used as a daytime alerting agent and is sometimes complimentary to OxyBait, but we don't think a substitute for many patients.

Thank you. The next question comes from the line of Charles Duncan with Cantor Fitzgerald. Your line is now open.

Hey, good evening, Bruce and team. Congrats on good commercial performance in the quarter, and thanks for taking our questions. Sorry to ask about a nuance in the pipeline, but it actually relates to the next readout that could come, and that's on JZP150 and PTSD. Tough disorder. I guess I'm wondering if, you know, given that this is an early phase two, would you focus more on STAT-SIG and effect size or the overall results of the study to enable the drug to move forward? And then in terms of the statistical analysis plan, it looks like a wide range of doses. So I guess I'm wondering, is it each dose relative to placebo or would you combine doses, the analysis of the two dose groups versus placebo? Thanks.

Rob, you want to take the 150 question?

Yeah, thanks, Bruce. We do think the CAHPS-5 is a comprehensive composite endpoint. It has regulatory endorsement as an endpoint that could be used for approval. And it does capture quite a bit, the broad range of symptomatology in PTSD patients. So we do think that that's a good way to measure the effect of the drug. We are measuring other things in exploratory ways as well, which we certainly will take into account. You're right that the trial is three arms. There's two active dose levels in placebo. And given the sample size that we have, we feel we're well-powered to make comparisons with both of those different dose levels against placebo. We don't have to collapse across those arms.

Well, I think that was our last question. So I just want to jump in and thank all of our questioners for moving us through. I think most of our commercial business, a lot of our pipeline, uh, and our strategy, you know, hopefully people feel great about the quarter on the top line, on the bottom line, the new guidance, increased diversification and the momentum we have in our business, particularly our three key growth drivers in, in Zywave, Epidiolex and Riley's. I'd just like to close today's call by recognizing all of our JAWS colleagues for their efforts in delivering new therapeutic options to patients and thank our partners and shareholders for their continued confidence and support. Thank you all for joining us today.

This concludes today's call. Thank you for your participation. You may now disconnect your lines.