Jazz Pharmaceuticals plc

Ladies and gentlemen, thank you for standing by and welcome to the second quarter 2022 Jazz Pharmaceuticals earnings call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question. To ask a question during the session, you need to press star 1-1 on your telephone. I would now like to turn the caller over to your host, Andrea Flynn, Vice President, Head of Investor Relations. You may begin.

Thank you, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its second quarter 2022 financial results. The slide presentation accompanying this webcast is available on the Investors section of our website. Investors may also refer to the press release we issued earlier today, which is also posted on 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 Rob Unone, Executive Vice President, Global Head of R&D. Kim Sablich, Executive Vice President and General Manager, North America, will join the team for Q&A. On slide two, I'll remind you that today's webcast includes forward-looking statements, such as those related to our future financial and operating results, including expectations related to Vision 2025 and our guidance for 2022, 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, we'll discuss non-GAAP financial measures. Reconciliations of GAAP to non-GAAP financial measures are included in today's press release and in the slide presentation available on the Investors section of our website. I'll now turn the call over to Bruce.

Thank you, Andrea. Good afternoon, everyone, and thank you for joining us today. I'll start on slide five. We entered 2022 with substantial momentum, and our team has continued to make notable advances across our business through the first half of the year, while delivering solid year-over-year top and bottom line growth in the first and second quarters. Our productive second quarter reflects meaningful progress towards achieving Vision 2025, which we introduced at the beginning of the year. We're pleased with our results in the first half of the year and are confident that we are on track to achieve our full year 2022 guidance. Starting with our commercial business, our Oxibate franchise is performing well, and we remain confident in the durability of ZyWave. which we believe will be the oxidate therapy of choice in the market, even following the entry of higher sodium authorized generics and potentially branded competition. We are pleased to see continued ZyWave adoption in narcolepsy and are equally excited about the positive momentum of the launch of ZyWave in idiopathic hypersomnia, or IH. There are a growing number of IH patients on ZyWave therapy and a high level of engagement and receptivity in the market, all of which is underpinned by strong reimbursement. Turning to Epidiolex, we continue to expand our prescriber base and are generating real-world evidence and data to further substantiate Epidiolex's broad effect across seizure types. Our team has done an excellent job of launching the product XUS, and we remain confident we can achieve blockbuster status for Epidiolex. Zulca remains the treatment of choice in second-line small-cell lung cancer. and our robust development effort is aimed at identifying additional patient populations who may benefit from therapy. Rylase has continued its strong launch, and we are pleased to be able to deliver the only therapy available to patients in the U.S. who experience a hypersensitivity reaction to E. coli-derived asparaginase. Dan will provide a detailed overview of our performance across our commercial portfolio later in the call. Our R&D team has remained very productive in the first half of 2022, advancing multiple clinical programs. In addition, we were pleased that FDA cleared the IND application for JCP815, allowing this program to enter clinical development. As we highlighted on our last earnings call, we completed in-licensing deals to add two new early-stage molecules to our pipeline in the second quarter, including JCP441 a potent, highly selective orexin-2 agonist that has the potential to advance the treatment of narcolepsy and other sleep disorders, and JCP-898, a differentiated, conditionally activated interferon-alpha-inducine molecule with the potential to minimize the toxicity associated with systemic interferon-alpha therapy, thereby expanding its clinical utility in treating cancer. These transactions demonstrate our commitment to expanding our pipeline and diversifying our revenue. Consistent with these objectives, we are prioritizing the medicines and R&D programs most likely to deliver value to patients and shareholders. I'm also pleased to share that we've achieved our deleveraging target two quarters ahead of our stated timeline, finishing the second quarter with a non-GAAP net leverage ratio of 3.2. The current macro environment is creating attractive options for corporate development, and our strong balance sheet provides us with flexibility to be active in identifying additional opportunities. Turning to slide six, Vision 2025 provides us with a clear roadmap as we transform our business and includes three components central to driving sustainable growth and enhanced value, commercial, pipeline, and operational excellence. Starting with commercial, After achieving over $3 billion in revenue in 2021, we're positioned to grow revenue to $5 billion in 2025 through a combination of existing products, as well as potential new therapies emerging from our pipeline and through corporate development. Our R&D organization continues to advance key programs addressing significant patient needs in neuroscience and oncology, and we anticipate delivering at least five novel product approvals by the end of the decade. through a combination of existing pipeline programs and corporate development. And on operational excellence, our 2021 adjusted operating margin was 43%, and we plan to improve that by five percentage points from 2021 to 2025, delivering more of our top line through to the bottom line. I'll now turn the call over to Dan for an overview of our second quarter commercial performance, after which Rob will share an update on the progress of our R&D programs. Renee will provide a financial overview, and then we'll open the call to Q&A.

Dan?

Thanks, Bruce. I'm encouraged by the progress we have made across our commercial portfolio in the second quarter. Starting with neuroscience on slide eight, we are maintaining positive momentum in our Oxibade franchise, continuing the robust launch in IH, and driving adoption of ZyWave and narcolepsy. With ZyWave, we have meaningfully advanced patient care with a lower sodium Oxibade product. The breadth of our ZyWave development efforts was recently highlighted by our presence in June at Sleep 2022, the 36th annual meeting of the Associated Professional Sleep Society. We and our partners debuted new data from 17 abstracts across narcolepsy and IH. It was a well-attended in-person event providing the opportunity to connect with customers and KOLs to gain valuable insights into their experience with ZyWave in both narcolepsy and IH. And we came away very encouraged by their feedback. In the second quarter, average active OxyVe patients increased to approximately 17,100, an increase of nearly 8% compared to the same period last year. In ZyWave for narcolepsy, we continued to see strong performance in the second quarter. our efforts around educating physicians and patients about the lifelong burden of high sodium intake are resonating. And we exited the second quarter with approximately 7,550 narcolepsy patients taking ZyWave. Looking ahead, we expect to see additional adoption of ZyWave from existing Zyrin patients, and importantly, the large majority of new-to-oxidate narcolepsy patients are beginning their therapy with ZyWave. For ZyWave and IH, we remain encouraged by the continued robust launch momentum and positive feedback from prescribers and the IH community. Actually, in the second quarter, there were approximately 1,150 IH patients taking ZyWave. We continue to focus on educating prescribers and patients about the compelling efficacy and established safety profile of the first and only FDA-approved therapy for IH. And we are confident in our ability to maximize ZyWave's potential in this underserved market. We've achieved our goal of obtaining similar coverage to narcolepsy with approximately 90% of commercial lives covered. We're pleased that payers have recognized the value that IH patients can realize from initiating ZyWave therapy. Patients find our comprehensive and customized support valuable. And we expect that educational efforts for prescribers and patients will increase the awareness building this market over time. Stepping back, in each of the last four quarters, our commercial and medical education initiatives around ZyWave have translated into growth of approximately 900 active patients per quarter across both indications. And we achieved a significant milestone in the second quarter with more active oxibate patients taking Zywave than Zyrem. We have an integrated field sales team that is supporting both narcolepsy and IH across a concentrated call universe with significant overlap among narcolepsy and IH prescribers, coupled with orphan drug exclusivity for both indications that extends to 2027 for narcolepsy and 2028 for IH. as well as Orange Book listed patents that extend out to 2033, we believe Zywave is well positioned to be a durable product and one of our core growth drivers. Now turning to slide nine in Epidiolex, net product sales grew by 12% in the second quarter of 2022 compared to the same period last year on a pro forma basis as we continue to add Epidiolex prescribers. As we have previously highlighted, we expect that as new prescribers gain experience with Epidiolex and see its clinical utility, they will more broadly adopt Epidiolex as a cornerstone therapy for their treatment-resistant patients. We are also committed to continuing to generate clinical study data and real-world evidence to further support the utility of Epidiolex across a broad range of difficult to treat seizure types. Our commercial team continues to focus on more in-person engagement. This is a promotionally sensitive market, and we are encouraged that our field sales force has experienced increased access to physician offices and treatment centers in recent months. And we're seeing continued adoption and growth ex-US. We remain on track to gain reimbursement for Epidiolex in France this year, at which point Epidiolex will be launched and reimbursed in all five major European markets. We also have opportunity for additional growth coming from a total of 10 anticipated new market and indication launches throughout this year. Given Epidiolex's unique mechanism of action, efficacy, and safety profile and ability to be combined with other therapies, we are confident we can achieve a blockbuster status for Epidiolex as a global standard of care in treatment-resistant epilepsies. Now moving to oncology and starting with Zepzelka on slide 10. Second quarter net product sales were 68.3 million. As Bruce highlighted, we have rapidly established Zepzelka as the treatment of choice in second-line small cell lung cancer. To support our efforts to further grow market share in our current indication, we are investing in additional real-world evidence and observational studies. We believe these data will add to the body of evidence around Zeb Velko's positive benefit-risk profile for second-line small-cell lung cancer patients and support increased adoption moving forward. Also, our robust development plan, which Rob will cover in more depth, has the potential to identify additional patient populations who could benefit from this therapy, including treatment of first-line small-cell lung cancer and other tumor types. providing the opportunity for meaningful future growth. Turning to slide 11, second quarter net product sales for Rylase, our recombinant Erwinia asparaginase therapy, were $73 million. Rylase demand reflects increased brand awareness among customers and its position in the market as the only therapy available to patients in the U.S. We have a hypersensitivity reaction to E. coli-derived asparaginase. Customer feedback continues to be positive, and prescribers have indicated they are now returning to best clinical practice, switching to non-E. coli-derived asparaginase earlier when there has been an initial hypersensitivity reaction observed. This is driven by the product profile, reliable supply of Rylase, and the suite of support services that we provide. Looking ahead, the potential label updates in the U.S. to a Monday, Wednesday, Friday dosing schedule and IV administration have the potential to improve the Rylase experience for clinicians and patients. We've also completed our marketing authorization application or MAA submission to the European Medicines Agency with potential for approval in 2023. Now, I will turn the call over to Rob to provide an R&D update. Rob?

Thanks, Dan. Slide 13 provides an overview of our R&D pipeline. Looking across the pipeline, we are advancing a number of programs. Within neuroscience, we plan to initiate the phase three trial for epidiolex and epilepsy with myoclonic atonic seizures shortly. This would add a potential fourth indication to our label and provide the first clinical data on a fourth seizure type, myoclonic atonic seizures. We're also planning to initiate a pivotal phase three trial for epidiolex in Japan this year that would include Dravet, LGS, and TSC. In addition, enrollment in our trials for suvacaltamide and JZP150 is ongoing. With respect to our nabiximols program, we announced top-line results from the phase three release MSS1 trial in June. The trial did not meet the primary endpoint of change in lower limb muscle tone six between baseline and day 21. as measured by the modified Ashworth scale. The goal of release MSS1 was to have an early look at the effect of nabiximols in patients with MS spasticity, and we continued to assess the trial results. In terms of safety, the profile was consistent with previously reported adverse events with no new safety signals attributable to nabiximols. Moving to oncology, as Dan mentioned, we are advancing a robust development effort for Lipsilca for the treatment of lung cancer. This includes an ongoing phase three trial supported by Joust and our partner Roche to evaluate Lipsilca in combination with Ticentric and first-line expensive stage small cell lung cancer. A confirmatory phase three trial in second-line small cell lung cancer being run by our partner PharmaMar and our own post-marketing observational trial and second-line small cell lung cancer. We recently presented data from four poster presentations at the ASCO Annual Meeting, evaluating HbZelka in a range of small cell lung cancer settings. We're also exploring HbZelka and other solid tumors with the initiation of our Phase II basket trial called eMERGE-201 earlier this year. This is a multicenter, open-label trial designed to assess the safety and efficacy of Zypselka as monotherapy in three cohorts of patients with solid tumors, advanced urothelial carcinoma, large cell neuroendocrine carcinoma of the lung, and HRD tumors that have progressed following a platinum-containing regimen. Turning to Rylase, in the second quarter, we completed an MAA submission to the European Medicines Agency. which included Monday, Wednesday, Friday, and every 48-hour dosing schedules, as well as IV and IM administration. This followed our submission of a supplemental BLA for Rylase in the U.S. to update our label to a Monday, Wednesday, Friday dosing schedule with patients receiving 25 milligrams per meter squared on Monday and Wednesday and 50 milligrams per meter squared on Friday. This schedule, which is more in line with current clinical practice to avoid weekend dosing, would allow patients to maintain a clinically meaningful level of serum asparaginase activity through the entire duration of treatment. Currently, the label dosing schedule is every 48 hours at 25 milligrams per meter squared. Clinical data using Monday, Wednesday, Friday dosing were presented at the recent ASCO annual meeting. We also completed a separate SBLA to support intravenous dosing. Similar to the review of our original BLA, both the Monday, Wednesday, Friday IM dosing schedule and IV formulation SBLAs are being reviewed under the real-time oncology review process. In line with our anticipation of multiple INDs through 2023, FDA recently cleared the IND application for JZPA15, our pan-RAF inhibitor for the treatment of solid tumors that contain mutations in the MAP kinase pathway, which will allow the product to enter clinical development. At the annual AACR meeting in April, we presented pretty clinical data demonstrating the JZP815 selectively and potently inhibits mutant A, B, and C raf kinases, and also demonstrated robust anti-tumor activity in the raf and raf mutant phenograph models. Now I will pass the call off to Renee for a financial update. Renee?

Thanks, Rob. I'll begin on slide 15. Our impressive second quarter financial results demonstrate our progress so far in 2022. We achieved strong top and bottom line growth with second quarter total revenues of $933 million, representing growth of 24% compared to the same quarter in 2021. This included neuroscience net product sales of 697 million and oncology net product sales of 230 million representing growth of 20% and 40% respectively compared to the second quarter of 2021. Importantly, we are on track to meet our 2022 total revenue guidance of 3.5 to 3.7 billion dollars. With respect to operating expenses, we continue to focus on strategic, disciplined use of capital and expect to come in toward the lower end of our full year OpEx guidance ranges. Our continued focus on both the top and bottom lines drove second quarter adjusted net income of $305 million, a 27% increase compared to the same period in 2021. Adjusted EPS with $4.30 in the second quarter, a 10% increase compared to the same period last year. Excluding the accounting change for convertible debt on a like-for-like basis, adjusted EPS growth would have been 23% compared to the same period in 2021. Based on the results from the first half of the year and our projections for the remainder of the year, we anticipate coming in toward the upper end of our 2022 non-GAAP ANI guidance range of $1.18 to $1.25 billion. In summary, we're very pleased with our performance year to date. We are affirming our non-GAAP adjusted guidance and have updated our GAAP guidance primarily to reflect the impact of foreign currency exchange movements on non-U.S. dollars are denominated amortization and inventory step-up expense. Turning to slide 16, we committed to rapid deleveraging following the GW transaction, and I am pleased to report that we have achieved our goal of a net leverage ratio of less than 3.5 on a non-GAAP basis, two quarters ahead of our stated timeline. Our non-GAAP net leverage ratio was approximately 3.2 at the end of the second quarter. This achievement has been underpinned by our disciplined capital allocation, focusing on both the top and bottom line, as well as our continued strong cash generation. Having achieved our deleveraging target, our focus will continue to be on managing the balance sheet through disciplined capital allocation and leveraging our strong cash flow which provides us with meaningful flexibility for further corporate development initiatives. Corporate development is a foundational pillar of our strategy to deliver long-term growth and value for both patients and shareholders, and is important to our efforts to achieve Vision 2025. Consistent with that, our corporate development efforts remain focused on diversifying and enhancing our product portfolio and pipeline, leveraging our unique insights in commercial infrastructure, and strengthening the overall sustainability of our business. With our strategic investments, expanding product portfolio, 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 will now turn the call back to Bruce for final remarks.

Thanks, Renee. I'll conclude our prepared remarks on slide 18. We're pleased to be building on the strong momentum we have created over the previous quarters across commercial, R&D, and corporate development, despite a challenging period in the biotech sector and global markets in general. In our commercial efforts, we are focused on execution across our neuroscience and oncology portfolios. including maximizing the ZyWave and IH and Rylai's launches, realizing the blockbuster potential of Epidiolex, and continuing to drive adoption of ZyWave and Narcolepsy and Zepzelka in small cell lung cancer. Our R&D team is advancing multiple mid- and late-stage programs, and we expect to submit several INDs through 2023. Operational excellence also remains a key area of focus, including maximizing our adjusted operating margins, while making strategic investments for future growth. In summary, we remain on track to achieve Vision 2025, and the affirmation of our top and bottom line guidance for 2022 underscores the confidence we have in our strategy and execution across the business. That concludes our prepared remarks. I'd now like to turn the call over to the operator to open the line for Q&A.

Ladies and gentlemen, if you have a question or a comment at this time, please press star 1 1 on your telephone.

We'll pause for a moment to compile our Q&A roster. Our first question comes from Jessica with JP Morgan.

Your line is open.

Hey, guys. Good afternoon. Thanks for taking my questions.

now that you've exceeded your net leverage target early should we think of that as unlocking potentially larger business development transactions sooner than 2023 thanks for the question jess uh you know really pleased to have achieved this target so quickly through both pay down on some debt but also you know continued growth in our profitability maybe for implications of this i'll turn it over to renee for a couple of comments

Yeah, thanks, Bruce, and thanks for the question. So, agree, yes, this does provide us with greater flexibility with respect to corporate development. As Bruce mentioned, the focus not just on paying down debt, but also increasing, enhancing our EBITDA gives us greater flexibility because dollar for dollar, we're getting more out of that net leverage ratio. by improving the EBITDA. And going forward, it also gives us greater capacity as we look at future targets. We've stated in the past and today on the call that we expect corporate development to be an important pillar for us going forward, both on the commercial front and then also on the pipeline. So we're excited to be well positioned to continue to execute on that front.

Thank you. One moment for our next question. Our next question comes from Mark Goodman with SVB Lyric.

Your line is open.

Yes, Ty. Can you talk a little bit about these patients that are at 1150? Are they naive patients to oxidase? Have they used oxidase before? Have they used other products before? Just give us a sense of who these patients are and what they're doing. Are they being dosed once a night or are they being dosed twice a night? And then just you didn't update the timeline on the next study, if you could just do that. Thanks.

Yeah, Mark, let's start with your IH question. You know, we've said we're very excited to enter this segment where there's then no FDA approved treatment. We know people have tried things off labeled historically, primarily a daytime stimulants and weight promoting agents, despite their relatively small impact on the disease. We also know that historically there was some attempt to use Oxibate to treat IH, but payer restrictions made that fairly uncommon. Maybe I'll ask Kim to update you a little bit on how the launch is going from a patient acquisition perspective and any comments she wants to make on the dose, and then Rob can chime in to answer your Nipiximol's question. Kim?

Sure, Bruce. Yeah, we continue to be very pleased with the uptake of this product, the first and only, you know, FDA-approved treatment for IH. You know, we're really encouraged by the robust launch momentum and really especially by the feedback that we're getting from prescribers who have actually utilized Zywaid in their idiopathic hypersomnia patient population. Our focus today, you know, remains in addition to sharing the impressive results safety and efficacy profile of ZyWave and idiopathic hypersomnia. We're also focused on continuing as we did prior to launch to educate prescribers and patients about the disease itself and IH and particularly ensuring they understand the full breadth of symptoms, not just excessive daytime sleepiness. We're also happy that Dan shared to be at a place as we had planned where now 90% of commercial lives are covered for idiopathic hypersomnia. We have a plan where now 90% of commercial lives are covered for idiopathic hypersomnia and have been pleased with our customers are telling us that this offering, you know, is meeting their needs both in terms of the product and the support services that we're offering.

Thank you.

Ladies and gentlemen, if you have a question about the support services that we're offering.

Thank you. Ladies and gentlemen, if you have a question or a comment at this time, please press star 1-1 on your telephone. There was a

There was a follow-up question from Mark just on the timing of the two ongoing, the big-small study. So, Mark, as you know, when we last updated on this, we were experiencing some, I would say, not unexpected challenges in getting those trials up and running, you know, related to some logistical issues during the ongoing pandemic. And we're working through those. We have some mitigations that we're putting into place, but we don't yet have a firmer timeline on those two trials at this time.

Then we also ask that you limit yourself to one question. One moment for our next question. Question, can I catch up with Calvin? Your line is open.

Hey, team. Great performance. I want to just drill down a little bit more on the IH launch. We're asked often if this is bolus that we're seeing or warehouse patients. Maybe Bruce or Kim, can you talk about are we seeing normal demand and to what degree do we think the pace that we've been observing will be consistent or not consistent going forward? And can you talk about to the degree in which the sales force is marketing versus still focused on narcolepsy conversion? Is this something where the sales force is indeed marketing aggressively or are we still kind of at a lower level than we'll have as we go forward. And then just lastly, any early view on patient retention? I know it's very early days, but any thoughts on that? Thanks so much.

Yeah, Kim, thanks for the questions. I'll start and then ask Kim to jump in. You know, we don't think there was any bolus or warehousing of patients in any significant way. You know, it's certainly true that there were some KOLs out there that were waiting for the launch of the product had seen the strong phase three clinical data, obviously saw our approval. You know that our actual launch post-dated our approval by a little bit while we completed REMS implementation. So there certainly was some starting point for getting patients onto therapy, but we don't think of that as a bolus in the way you're suggesting it. In terms of the pace of adding patients, I'd just like to remind people we're only a couple quarters into this launch, so probably a little too early for a lot of super accurate trending. As Dan said in his remarks during the script, you know, we're just really pleased to be seeing growth in narcolepsy patients, whether that's patients coming over from Xyrem or patients new to OxyVe therapy, including newly diagnosed narcolepsy patients. or whether they're IH patients getting the benefit of CyWave for the treatment of idiopathic hypersomnia. You know, we're seeing really strong growth in the overall CyWave franchise. Maybe Kim could comment on how she and the team are balancing our efforts across narcolepsy and IH and whether that will change in the future and can add any comments on retention that she'd like.

Sure, Bruce. So I think as we've shared before, this is a very efficient launch for us in that it's largely the same base of customers. There's 90% overlap between those HCPs that we're calling on for narcolepsy and IH. And, you know, really to your question, Ken, of how we're balancing that, it is a balancing act, but I can say that we are out there fully supporting both, you know, the continued transitions and new patient starts and narcolepsy and as well as the launch of IH. And our teams know that first and foremost, we've got to keep the momentum going on narcolepsy, but I can say that we've got a very strong full effort for both. In terms of patient retention, I don't think we've shared specific numbers, but I would just instead comment on more of the qualitative feedback that we've gotten from HCPs in terms of them being very pleased with the product and that they see that its performance in their patients is consistent with what they saw in the clinical studies.

Thank you. One moment for our next question. Our next question comes from Jason Garberry, Bank of America. Your line is open.

Oh, hey, guys. Thanks for taking my question. I wanted to just drill in on the dialect if you can talk a little bit about these enhanced marketing efforts, is this going to be more of a second half driven benefit? And as we think about the performance this quarter, just curious, are we seeing meaningful first-time contribution ex-U.S.? The U.S. growth is perhaps even lower than what was the overall reported number. Just wondering if you could help us sort of figure out like what's going on now and some of the marketing initiatives as we think about second half. Thanks.

Yeah, Dan, maybe I could ask you to jump in on Epidiolex just globally, including the rollout ex-US in recent quarters.

Sure. Yeah, no, we're, I mean, we're very pleased to see the growth and continue to, you know, hear great feedback from the increasing prescriber base in the US and the persistence remains strong. And we said this in the past, that it is a promotionally sensitive product. And importantly, our field force is increasing the level of face-to-face engagement, which is really important, especially for the smaller offices and the prescribers who haven't had experience or much experience with Epidiolex to move it more broadly into their treatment-resistant epilepsy. Regarding the XUS, we don't break out the sales, but we always view it as a meaningful growth driver to the overall franchise as a global brand. You know, did reference that we've got 10 new market and indication launches. A couple of them have already gone with Norway and Ireland, a successful two plans, six indication launches. And, you know, we've still got a number of countries pending, especially France, which would be the last of the big countries. So Yeah, so we're very confident about achieving ultimately the blockbuster status as a cornerstone of treatment-resistant epilepsy.

Thank you. One moment for our next question. Our next question comes from Brandon Fulks, okay, until your line is open.

Hi, thanks for taking my question, and congratulations on a good quarter. Can you maybe just talk about the competitive dynamics You're seeing when new patients start with a narcolepsy. It was a strong quarter on your part from new patient ads, it looks like. We saw a competitor with the report strong new patient ad. So can you just elaborate a little bit on the market? Is this just sort of the normal step up post the 1Q headwind, you know, thrown in with, you know, we had Omicron earlier this year? Or is there maybe just a bit more of a durable interest in the branded narcolepsy space, given you have two branded competitors out there promoting aging? and maybe just any commentary on in terms of getting in front of physicians in person. Thank you.

Yeah, Brandon. You know, I would say we couldn't be more happy with the continued growth of ZyWave in narcolepsy as well as in IH over these past quarters. Just the number of patients on therapy is very gratifying. You know, we think some of that is because we've come along with a truly differentiated a better product due to the low sodium. You know, with FDA's work in drug exclusivity, finding clinical superiority on the basis of safety, because of this very large reduction in nightly sodium intake in a chronic disease where we know this patient population is at significant risk of cardiovascular comorbidities, you know, we really got something that I think is attracting both former Xyroim patients, but also potentially new patients. It is generally true that Oxibate patients are on, not in all cases, but generally true that they are on other agents. Often our agent is taken at night and there are other daytime agents we're taking and I think that the product you're referring to, Pitolisant, falls into that category of a daytime treatment that's also been adding new patients. So, you know, patients experiment with combinations that make sense for them, but, you know, we've continued to see the kind of excellent growth we've really wanted to see, again, across existing oxibate patients and new oxibate patients.

Thank you. One moment for our next question. Our next question comes from David Amsell with Piper Sandler.

Your line is open.

Hey, thanks. I wanted to drill down a little more about IH. And I apologize if I missed this, but in terms of IH, are these patients new diagnoses who are now getting treatment or these patients who have already been on wakefulness promoting agents like modafinil? And then as a corollary to that, question. Do you think that with the availability of ZyWave, you're seeing more diagnoses in general? Can you comment on that as well? Thanks.

David, maybe I'll start with a broad picture and then let Kim go to our more current strategy. Broadly, we do think the availability of the first ever FDA-approved agent, NIH may well spur more diagnosis going forward. It's often the case that when there's a reward for diagnosis and that it unlocks a treatment option and it unlocks reimbursement for a treatment option, you'll see doctors move all the way through that diagnosis where otherwise they might not. In terms of our current strategy for penetrating the IH space, maybe I'll let Kim make a few remarks.

Yeah, sure. So, you know, we've got a really nice-sized market of diagnosed patients to go after, you know, and we're focusing our initial launch, I think, as we've said several times, you know, not only on an existing sleep call universe, but also on the 37,000 adult patients who already not only have a formal diagnosis of idiopathic hypersomnia, but we're also, you know, in the healthcare system, we can see actively seeking healthcare. So, you know, that's why our strategy is really much more focused on encouraging HCPs to get appropriate patients started on ZyWave. And, you know, we really have a three-pronged approach out there in the marketplace right now. As I mentioned earlier, we're continuing our efforts to improve general understanding of the disease of idiopathic hypersomnia, particularly as it relates to the breadth of patient symptoms experience, given that we have a very broad indication in this condition. We're also educating on the compelling efficacy and safety profile. And we're helping HCPs identify those patients in their practice who are already diagnosed, who may be ready for ZyWave. They've had many, many years to figure out what that you know, oxibate patient and narcolepsy looks like. They're just getting started in the case of idiopathic hypersomnia. So, those are really the three key areas that we're focusing on in a very large population that's already diagnosed.

Thank you. One moment for our next question. Our next question comes from Jeff Hong with Morgan Stanley.

Your line is open.

Thanks for taking my question. You've indicated for multiple quarters that you're adding new prescribers for Epidiolex. Can you talk more about the new U.S. prescribers and do they tend to translate to multiple prescriptions fairly rapidly and have those dynamics change much over time? Thanks.

Tim, maybe I'll hand that over to you in terms of who the new Epidiolex prescribers are and what that means to our business.

Yeah, sure. The newer prescribers, I can really just say the characteristic is that they're, you know, obviously slower adopters as you see in any marketplace. And, you know, we do believe the key is to getting in there face-to-face, educating them on the product profile, and getting them to start using the product because what we see, you know, from the beginning of the launch until now is that once a new prescriber gains experience with Epidiolex, and is able to see firsthand its clinical utility, they more broadly adopt Epidiolex as a cornerstone therapy for their treatment resistant patients. What I'd say is one of the approaches that we've been taking pretty much since the beginning of the year with HCPs who don't have experience with Epidiolex or we believe are under utilizing it in their practice is we're leveraging the fact that this is a category that naturally utilizes polypharmacy. And we're highlighting data that we have on the synergistic effect of using Epidiolex in combination with Clobazam. Clobazam is a product that's already on board in the vast majority of patients. And we have found that by sharing these data with these HTPs that have yet to utilize Epidiolex at all or, you know, robustly, is that they've been highly impressed with the data as they demonstrate an ability to reduce the number of seizures in both LGS and Dravet syndrome by more than 60%, which is a number, an efficacy number that's a very uncommon outcome, and they recognize this the moment we share that data. So it's a very promotionally sensitive market. We're encouraged that our sales force has had increased access to offices and treatment centers in recent months, and we're really confident that our level of promotion is going to continue to increase in the second half of the year, and we've got a strong set of data to try to, you know, really move those slower adopters, you know, into trying Epidiolex.

Thank you. One moment for our next question. Our next question comes from Gary Natchman with .

Thanks. Good afternoon. So Riley's was really strong in 2Q. Any unusual stocking in there in the quarter? Does that all reflect demand? You mentioned that docs are switching patients back earlier if they have a reaction to asparaginase. So could you expand on that dynamic? And how should we think about that run rate from here, especially if you get Monday, Wednesday, Friday dosings?

Yeah, Gary, thanks for the question. You know, we could not be more pleased with where we are just a couple quarters into the Rylase launch and how quickly we think physicians have moved to the best possible treatment paradigm for these ALL patients. Kim, maybe I'll let you answer as to whether there was any unusual stocking and how we think about this run rate for Rylase.

No, I don't think we saw anything unusual, you know, going on this quarter. You know, I think current utilization in the U.S. is, you know, outperforming. If you look at the numbers, the peak that we experienced with Erwinase, you know, reinforcing the impact that, you know, supply constraints had on providing optimal patient care. And we think that really the demand trend we're seeing, you know, reflects not only the increased brand awareness and familiarity of Riley's with customers, And its position in the market is the only available therapy right now for patients who have a hypersensitivity reaction to E. coli-derived asparaginase. You know, but really at this point, we think a lot of it has to do with the things that Dan highlighted in terms of, you know, we see customers who had put in place, you know, asparaginase sparing activities such as desensitization and re-challenge practices are now telling us and we're seeing through ordering patterns that they are you know, stopping those practices and they're starting to utilize RILAs instead. So all that very positive signals that the market is excited about RILAs and ready to get back to, you know, optimal practices.

And, Kim, just to add on, this is Dan. We do have global rights to the product, and as we updated on the call, we did complete our submission to the EMA in the second quarter. You know, market dynamics are a little different there when ACE is on the market. But again, we think with our fully recombinant and, you know, easier to administer and, you know, already in a formulation, but also, you know, importantly, we studied it into a, you know, an updated 25-25-50 dosing schedule that optimizes disparage and ACE levels. through patients. So we look forward to that being on the market in 2023 in Europe. And then we're assessing other marketplaces, including Japan.

Thank you. One moment for our next question. Our next question comes from Madhu Kumar with Goldman Sachs.

Your line is open. Hey, everyone. Thanks for taking our questions. I want to follow up on some of the earlier discussion around Epidiolex. And I guess kind of the question we're ultimately, I think, curious about is, to what extent do you see further growth in Epidiolex? Is it around geographic expansion, indication expansion, or kind of just like expansion of the onboard prescriber's use of the drug kind of off the lines of tumor-resistant epilepsy?

Dan, you want to take a global opportunity for Epidiolex and where we see that going in the future?

Yeah, sure. I mean, I'd say yes to everything you just referenced. I mean, there's plenty of headroom in the current indications as we think about the combination of Clobizam. Clobizam is much more broadly used right now than, you know, than Epidiolex. And we do have continued data generation across different seizure types, as well as sharing real-world evidence from the medical records. And then importantly, ex-US, we're at 14 of 34 countries in terms of launches. You know, France just pending this year and opportunity for us to move more broadly into Asia as well. So, you know, we're super excited by what this brand can do long-term. It's a cornerstone, unique mechanism, very combinable. And we've seen, for example, with Clobizam enhanced anti-seizure activity, which is always you know, sure is a critical factor for these patients.

Thank you. One moment for our next question. Our next question comes from Amifadia with Needham. Your line is open.

Hi, good evening. Thanks for taking my question. Going back to idiopathic hypersomnia, can you give us some more color around the market dynamics. Where are these patients coming from in terms of who are the prescribers? Are they existing Xyrem or Zyvae prescribers for narcolepsy? And if you could give us some color of what percent of your existing prescribers for narcolepsy have prescribed a patient for IH. And also give us a sense of the patient journey, especially given the fact that There haven't been other treatments for IH available in the market. So how often are these patients going back to their physicians seeking treatment or something new? That would be helpful. Thank you.

Yeah, Kim, do you want to provide any additional information on overlap of prescribing positions and, you know, maybe pattern of when patients see their physicians?

Yeah, I don't believe we have that data to share, Bruce. Maybe somebody can let me know if they feel otherwise. But in terms of how frequently patients are seeing their doctor, we see that typically out there in the marketplace, what we hear is an idiopathic hypersomnia visits their doctor, you know, twice a year. You know, really the main statistic that we have about the HCP populations is that in terms of potential, and where the IH patients are receiving treatment, there's 90% overlap in terms of where the patients reside and which HCP offices, but I don't have data at this time in terms of, you know, what percentage of physicians have prescribed for both IH and narcolepsy.

Thank you. One moment for our next question. Our next question comes from Gregory Renza with RBC.

Your line is open.

Great. Thanks, Bruce and team, for taking my question, and congrats on the quarter. Bruce, I just wanted to touch back again just once more on Epidiolex. I'm just curious, just in the context of the competitive landscape with respect to developmental therapies, I'm just curious if you could comment a bit on Epidiolex, maybe longer term, just given there have been some positive developments and some setbacks, amongst the landscape of late. You certainly commented on combination and cycling, but any added thoughts as that landscape even evolved would be great. Thank you very much.

Yeah, I would just remind people that the conditions we're treating with Epidiolex are, you know, very severe epilepsies, very treatment refractory. Patients have often tried a number of therapies before they get to Epidiolex. Of course, we've seen benefit and a good safety profile with Epidiolex so that as patients, their families, and physicians continue to seek both better seizure control and just overall better results for their child, they tend to stay on Epidiolex even if they might rotate off or try Epidiolex. a different therapy. I'm personally heartened that there are continued developments that might offer additional relief to these patients, give them more things to put into the armamentarium of agents to try, but we haven't seen anything yet on the horizon that strikes us as reducing the opportunity for Epidiolex, I think we may see benefits of combined treatment, much like you heard touched on in Kim's comments about Clobazam a little bit earlier. So lots of room for improvements on current results from these patients. And some of our evidence generation and additional trials is to continue to bring out that benefit, whether that's in another seizure type like EMOS or whether that's just better elucidating what we are seeing in patients treated with epidiolex. Rob, maybe I could ask you to jump in just from a physician perspective about treatment of these childhood onset seizure disorders and how you see that going forward.

Sure. Happy to, Bruce. You know, it's clear that Epidiolex has been very effective in these groups of highly refractory epilepsy, both in terms of seizure reduction and other measures around seizure frequency, seizure-free days, for example, but also in terms of overall well-being. Last year's AES, we showed a caretaker survey where there was clearly benefits observed outside of just measures of epilepsy itself. So becoming a cornerstone for therapy. And as you mentioned, the safety profile allows for combining with other therapies. So at the moment, physicians, practitioners continue to have a lot of enthusiasm about it. And to the extent that there are new drugs coming into these spaces, probably thinking about it more in terms of another another add-on to be combined rather than to replace in what's a pretty highly refractory set of conditions.

Operator, I think we probably have time for one more question.

Our last question comes from Ashwani Verma with UBS.

One moment. .

Sorry, I was going to ask, like, on the big symbol, anything that you can share from the phase three, this release, MSS1 trial? I understand that you didn't see statistically significant benefits, but did you see directional benefits?

Yeah, Rob, do you want to jump in on data from the recently top-line unblinded NIPIC small trial?

You know, we haven't given further details on that, and we certainly are combing through the data in greater detail to understand what we can learn from this and how that might ultimately impact the rest of the program if it does at all. So nothing more to add at this time.

Yeah, and Ash, I'll just remind you that this is not the first trial ever done at the BIC Smalls, so we're looking back across all trials with the agent as well as our ongoing trials to chart the best course forward. So with that, maybe we'll wrap up the call, and I'll thank everyone for joining us. You know, we're really excited about the upcoming opportunities across our business. As we continue to drive growth and shareholder value, you know, we remain on track and focused on achieving Vision 2025. And as always, I'd love to close today's call by recognizing all of our Jazz colleagues for their commitment to delivering new therapeutic options.

Ladies and gentlemen, let's conclude today.

Thank our partners and our shareholders for their continued confidence and support. Thank you all for joining us today.

Ladies and gentlemen, this concludes today's presentation. You may now disconnect and have a wonderful day.