Jazz Pharmaceuticals plc

Good afternoon, ladies and gentlemen, and welcome to the 3rd Quarter 2021 Jazz Pharmaceuticals Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question, you will need to press star 1 on your telephone. I would now like to turn the conference over to your host, Ms. Andrea Flynn, Head of Investor Relations. Ma'am, please go ahead.

Thank you, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its third quarter 2021 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 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 Rob Yannone, Executive Vice President, R&D, and Chief Medical Officer. Kim Sablich, Executive Vice President and General Manager of North America, and Phil Jockelson, Neuroscience Therapeutic Head, will join 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, we'll discuss non-GAAP financial measures. Reconciliations of GAAP to non-GAAP financial measures are included in today's press release and the slide deck available on the investor 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. We remain laser-focused on executing our strategy across commercial, R&D, and corporate development. positioning Jazz to deliver sustained growth as we continue to build our high-value portfolio of commercial and clinical stage therapies. In the third quarter, we continued to make progress in our transition to a diversified, innovative biopharma company by focusing on our three primary pillars. First, growing sales of existing products in our commercial portfolio, including through indication and geographic expansion. The market-leading adoption of ZyWave in narcolepsy and top-tier launch of ZebZelka in small cell lung cancer highlight our commercial execution across both our neuroscience and oncology therapeutic areas. The recent approval and launch of ZyWave for idiopathic hypersomnia, or IH, showcases our ability to expand to new indications, in this case where there are no other FDA-approved therapies. Further, our progress in securing access and reimbursement for Epidiolex across major European markets demonstrates our team's capabilities beyond the US. Our acquisition of GW Pharmaceuticals epitomizes our second strategic pillar, acquiring differentiated commercial products and late-stage programs. This acquisition brought in a high-growth, durable commercial product in Epidiolex and expanded our R&D portfolio. Our third pillar is pursuing pipeline development of differentiated therapies. Excluding the acquisition of GW, since 2015, our team has increased our pipeline assets fourfold, resulting in 11 product approvals. Now, with the addition of the GW pipeline and cannabinoid platform, we are excited about a more robust pipeline that will further enhance that R&D productivity. Turning to several key highlights this quarter, In 2020, we established an aggressive target of completing five commercial launches in 2020 and 2021. I'm pleased to announce that earlier this month, we launched ZyWave for IH and adults, which completes that goal. This represents a major milestone for Jazz, underscoring our ability to advance therapies from concept to commercialization and successfully execute on launches and of differentiated products that address critical patient needs. The launch of ZyWave for IH provides a significant growth opportunity for our Oxibate franchise, which we view as a durable core component of Jazz's long-term value that has multiple Orange Book-listed patents that extend through 2033. We continue to expect that a majority of Oxibate patients across all approved indications will benefit from ZyWave in 2023, which accounts for branded and generic higher sodium oxidate therapies entering the market. With respect to the entry of authorized generic Xyrem, we plan to provide guidance for 2022 as usual on our fourth quarter earnings call. At that time, we anticipate providing more information on the Xyrem authorized generic launch. The integration of GW continues to move ahead And as I noted in the past, there is a superb cultural fit between the Jazz and GW teams. The acquisition is proving to be highly complementary to our existing commercial portfolio and added the exciting GW cannabinoid platform and science to our R&D pipeline. That said, we acknowledge there is work to be done. While we have continued to grow Epidiolex in the U.S., there have been challenges in the face of the COVID-19 pandemic. Dan will provide more detail about how our commercial team is addressing these challenges to support further Epidiolex growth in the U.S. We continue to strengthen the durability of Epidiolex and now have 20 Orange Book listed patents, with the majority extending through 2035. We are also generating additional IP, including a composition of matter-like patent that we expect will be issued later this year and listed in the Orange Book in the first quarter of 2022. This patent would expire in 2039. And I want to be very clear, we remain excited by the potential long-term value creation that the GW acquisition can deliver. And our confidence in Epidiolex's blockbuster potential and its importance as a component of our commercial portfolio has only increased since we brought it in-house. Turning to oncology, our Zepzelka team is executing a top-tier commercial launch. We are also advancing a robust clinical development plan, and Rob will provide more color on our R&D efforts for Zupselka and across our portfolio later in the call. On June 30th, we were pleased to announce approval of Rylase under FDA's real-time oncology review. While we're early in the launch, we believe that Rylase will become the standard of care for patients who need a non-E. coli-derived asparaginase. With respect to our financial performance, our third quarter delivered a 39% increase in total revenues compared to the same quarter last year. We continue to diversify our revenue with more than 50% of net product sales coming from products launched or acquired since 2019, in stark contrast to a year ago when the same metric was just 8%. These newer products are not only innovative medicines, that address critical needs for patients with neurologic disorders and cancer. There are also durable, long-lived therapies that support our strategy of building a diversified, high-growth commercial portfolio. Our strong cash flow and disciplined capital allocation is enabling us to invest in the growth of our business while staying on track to meet our deleveraging goal. With a strong foundation, exciting new opportunities, and continued execution against our plan, I remain highly confident in Jazz's future. I'll now turn the call over to Dan for an overview of our commercial performance, after which Rob will share an update on progress across our R&D programs. Renee will provide a financial overview, and then we'll open the call to Q&A. Dan, over to you.

Thanks, Bruce. Well, I'm excited to share the progress across our commercial portfolio. So starting with neuroscience, we saw strong momentum during the third quarter for our OxyBait franchise. Average active OxyBait patients increased to approximately 16,000 in the quarter, a 6% increase over the same period last year, and we exited the quarter with approximately 6,000 active ZyWave patients, up from approximately 5,100 at the end of the second quarter. We see significant opportunity for ZyWave to continue to grow in narcolepsy and remain focused on educating physicians and patients about the lifelong burden of high sodium intake, particularly in a patient population like this one with an increased risk of cardiovascular comorbidities. In addition to the strong adoption of ZyWave from existing Zyrum patients, we continue to see the large majority of oxibate-naive patients being prescribed ZyWave as opposed to Zyrum. As slide 7 illustrates, we've achieved market-leading adoption for ZyWave in narcolepsy relative to launches of other next-generation neuroscience products. This speaks to the strong product profile, which includes FDA's published findings of the clinical superiority of ZyWave to Zyrum based on greater safety because of reduced sodium, as well as our deep understanding of the sleep space and our ability to successfully drive adoption of new therapies. and we believe the IH indication will drive further growth of ZyWave. Our commercial launch began on November 1, and I'll remind listeners that a replay of our October webcast discussing the commercial launch strategy of ZyWave for IH is available on our corporate website for those who missed it. As we roll out this launch, our initial focus is on driving awareness and adoption among existing OxyBase prescribers. and the approximately 37,000 people who have been diagnosed with IH and are actively seeking healthcare. Expanding the market beyond diagnosed IH patients who are actively seeking treatment provides us with a longer-term growth opportunity, and we estimate that the total diagnosed IH patient population is likely close to that of the diagnosed narcolepsy market, which is approximately 70,000 to 80,000 patients. So as a reminder, beginning with our fourth quarter in 2021 year-end reporting, we will share the breakdown of the number of ZyWave patients based on their diagnosis of either narcolepsy or IH. So moving to Epidiolex, this is our first full quarter with the product since the close of the GW acquisition. Epidiolex net product sales were 160.4 million, and we achieved a 21% increase over the same quarter in 2020 despite the ongoing impact of COVID-19. COVID-19 continues to put short-term pressure on Epidiolex growth. There are several factors related to the pandemic that are at play. On a macro level, pediatric new prescriptions have been disproportionately impacted by COVID relative to other specialties over the last 12 months, as the chart on slide eight illustrates. Epidiolex growth has been affected by this trend, Reports from the field indicate that due to COVID-19 and the lack of access to vaccines, especially for children under 12 years of age, many parents are hesitant to bring their children into an office setting and risk COVID exposure or change anti-epilepsy treatment regimens and risk breakthrough seizures. These dynamics have negatively impacted new patient starts, the majority of which are pediatric patients. At the same time, promotional visits to institutional centers in the U.S. are down across the industry. We see this playing out with Epidiolex. Through the first three quarters of 2021 relative to 2019, our average number of total monthly sales interactions with healthcare providers were down 44% overall, with face-to-face interactions down 71%. This has a notable negative impact on the growth rate of a newer product like Epidiolex, where education and in-office support for physicians with little or no product experience help expand trial usage and adoption. And the impact here is not limited to Epidiolex. Sales across other anti-epileptic drugs with similar indications to Epidiolex have been flat in recent quarters. Now, turning to slide nine, while there are challenges, our team has made steady progress in driving adoption in our three current indications, Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex, or TSC. We continue to have high persistency rates among patients who begin therapy, and we see opportunity for additional patient growth across these indications. there has been strong adoption of epidiolex in large epilepsy centers, and we have increased our reach now to smaller centers and general neurology practices. As we expect COVID-19 pressures to ease in the U.S., and now with younger children becoming eligible to receive COVID vaccines, we expect to see an upturn in both patients visiting their healthcare providers to discuss new treatment options, and our ability to provide in-person education to physicians, the combination of which we believe will contribute significantly to Epidiolex growth. Based on positive trends in new and unique prescribers, as well as feedback from our prescribers, we are confident that we will continue to grow the Epidiolex prescriber base. So in response to the current environment, we've implemented a number of virtual educational initiatives for healthcare providers and patients, to further their understanding of Epidiolex's unique product profile and mechanism of action in the anti-epileptic drug class. In recent market research among prescribers, approximately 40% of respondents indicate they are moving Epidiolex up in their treatment algorithm. We believe this is underpinned by more prescribers having experience with Epidiolex over time and gaining confidence in the product. There's also a very large unmet need in refractory epilepsies. In the U.S. alone, there are approximately 160,000 treatment-resistant pediatric epilepsy patients and approximately 1 million treatment-resistant epilepsy patients overall. Many of these patients have rare pediatric-onset epilepsy syndromes for which no FDA-approved treatment exists specific to that particular syndrome. Epidiolex has the potential to treat a broad range of seizure types, and the goal of our development program is to add to that existing body of evidence. Our planned registrational trial in epilepsy with myoclonic atonic seizures, or EMOS, will provide data in the seizure type. In addition, we continue to invest in company-sponsored trials and to support investigator-initiated studies to evaluate the efficacy and safety of Epidiolex in different epilepsy subtypes and across different endpoints. We also see a significant opportunity for epidemics growth coming from markets outside the U.S. Looking at slide 10, we've been extremely pleased with our progress in Europe. We have secured favorable pricing and access to date, and national reimbursement is in place in four of the five largest European markets, including Germany, the U.K., Italy, and Spain. In those four markets, pricing is greater than 70% of the US wholesale acquisition price. In addition, we anticipate commercial launch in France next year. Overall, we remain excited about the future growth potential of Epidiolex. While we are currently navigating short-term headwinds, we are confident that with Epidiolex's unique mechanism of action, its ability to be combined with other therapies, and increasing positive experiences in real-world settings, Epidiolex can become a standard of care for treatment-resistant epilepsies. So now turning to oncology and ZebZelka, our team has done an outstanding job on the launch of this innovative therapy. As a graph on slide 11 shows, net sales of ZebZelka substantially outperformed the launches of other comparable oncology products. Our team has done an outstanding... sorry, we continue to see strong growth in demand for Zebzelka in third quarter with net product sales of 71.7 million. As noted in our press release, we've lowered our return provision to reflect actual experience. This had the effect of increasing the quarter's net sales number by approximately 10 million. Excluding this adjustment, third quarter net product sales increased approximately 10% compared to the second quarter. As you can see on the chart on slide 12, Zepzelka is now the treatment of choice in second-line small-cell lung cancer, and we're pleased that Zepzelka's share in this setting continues to increase, taking market share from topotecan and immuno-oncology products used as monotherapy. We continue to see near-term growth opportunities as we expect Zepzelka will continue to gain share among patients being re-challenged with platinum-based chemotherapies or receiving other chemotherapy regimens. Now moving to Rylase on slide 13, our internally developed recombinant erwinia asparaginase therapy launched in mid-July. Third quarter net product sales were 20.7 million. Initial feedback from accounts is encouraging, and we have received positive reports on the ease of both ordering and dose preparation, as well as our support services. In terms of the market dynamics, erwinase was still available in the supply channel through mid-September. which included the last imported batch of Irwinase sold by Clinigen that FDA allowed the importation of in May. We believe the overwhelming majority of Irwinase supply was used up by the end of August, and there was a notable uptick in Rylase orders beginning in September. To support the launch, we're executing numerous commercialization activities to educate healthcare professionals about the clinical profile and the administration of Rylase. and we're working to place Rylase on institutional formularies and into their regular ordering systems. In summary, having delivered on the ZyWave for narcolepsy and Zepzelka launches, we are confident in our commercialization team's ability to achieve successful launches for Rylase and ZyWave in IH. And while we've been facing some near-term headwinds from COVID for epidiolex, we do expect to be able to drive growth for this brand and across our product portfolio in future quarters and to deliver meaningful value as we transform the lives of patients and their families. I'm now going to turn the call over to Rob for an update on our development programs. Rob?

Thank you, Dan. On slide 15, we've detailed key clinical programs in our pipelines. Starting with our neuroscience development programs, the integration between our JAWS and GW R&D teams is progressing really well. We are advancing multiple therapies across our neuroscience portfolio, including a number of programs emerging from the GW cannabinoid platform. Epidiolex is currently approved to treat seizures associated with three refractory epilepsy disorders, and we remain on track to initiate a registrational phase three trial for a fourth indication, epilepsy with myoclonic atonic seizures, or EMOS, in the first half of 2022. EMOS is characterized by generalized myoclonic atonic seizures, and this trial will provide the first randomized controlled clinical data with epidiolex in this seizure type, which we believe will provide further data on the potential effectiveness of epidiolex in treating a broad range of seizure disorders. Now turning to Nebiximols, the program has three active clinical trials focused on multiple sclerosis-related spasticity. We expect data from the first trial, which is a smaller, shorter trial relative to the other two, in the first half of 2022. If results from this first trial are positive, there is the potential for a regulatory submission in the U.S. in the next 18 to 24 months. And we expect data from the two additional trials, which have larger sample sizes, to read out in late 2022 and early 2023. Now to discuss JZP385, we recently initiated our Phase II clinical trial for JZP385 in essential tremors. and expect data to read out in the first half of 2024. In the U.S. and top five European markets, it's estimated that there are approximately 2 million people diagnosed with essential tremor, with about a half a million being drug-treated. We are also on track to initiate our Phase II trial for JZP150, a fatty acid amide hydrolase, or FAW inhibitor, and post-traumatic stress disorder by the end of this year. Now moving to oncology, I'd like to start with Zivselka and update our development plans in small cell lung cancer and other potential indications, which includes four clinical trials that are underway or will be initiated in early 2022. In collaboration with our partner, Roche, we are supporting a Phase III trial to evaluate first-line use of Dipselca in combination with atezolizumab, or Ticentric, compared to Ticentric alone as maintenance therapy in patients with extensive stage small cell lung cancer after completion of induction chemotherapy. This trial has already been initiated and is now listed on clinicaltrials.gov, and we anticipate the first patient will be enrolled later this year. Other trials include a confirmatory trial in second line small cell lung cancer being run by our partner, Pharmamar, that is expected to initiate later this year. A phase two BASCA trial to explore efficacy and safety of laminectin monotherapy in patients with select advanced and metastatic solid tumors that we expect to initiate in early 2022. as well as a Phase IV observational study in small cell lung cancer that is underway. Now, I'd like to point out that we expect the Phase IV study to provide additional data regarding the efficacy of Zypselka in certain populations, including those patients considered to be platinum sensitive or often retreated with platinum-based chemotherapy in the second line. I'd like to highlight that these patients did particularly well with Zypselka, as seen in the cohort of patients that supported accelerated approval. Further evidence of improved outcomes across a large number of platinum-sensitive patients, such as from the Phase IV observational study, would provide even stronger rationale for expanding the use of Zypselka in this key second-line setting, as platinum retreatment is the second-most used therapy behind Zypselka. Moving to Rylase. We received FDA approval in June prior to the completion of our clinical trial through the real-time oncology review process, which allowed us to prioritize making this therapy available to patients. We took Rylase from first in human trials to approval in just two and a half years, and we have that same urgency as we advance the development program. We are very pleased to have received real-time oncology review status yet again this time to submit an SPLA to update our label to intramuscular Monday, Wednesday, Friday dosing schedule, a schedule that is more in line with current clinical practice, and this is a high priority for the program. We expect to complete the SPLA submission in early 2022. The ongoing trial is also assessing intravenous administration of Rylase, which is common for asparaginase in Europe and other geographies. We anticipate the data from our current development program will support regulatory submissions in Europe, and we are moving rapidly to submit in mid-2022 for both the IM and IV routes of administration, with potential approvals in Europe beginning in 2023. We are presenting data from the RYLAVES trial at the upcoming American Society of Hematology Annual Meeting in December, including findings from the important 25, 25, 50 milligram IM dosing regimen from 52 patients. I'd like to wrap up by highlighting that we have significantly advanced our combined R&D capabilities and productivity, and we have an incredibly talented team in place. As I've outlined here today, multiple late-stage trials and registrational trials are ongoing or expected to begin soon. And as we enter 2022, we look forward to sharing updates on our earlier stage development programs and research initiatives. I'll now turn the call over to Renee.

Thanks, Rob. Full financial results are available in our press release and 10Q, and several key metrics are highlighted on slides 17 and 18. On today's call, I'll discuss our overall financial performance, and provide additional color around our updated guidance. We have made significant strides in transforming our business through the first three quarters of 2021, and we're well positioned to finish the year with positive momentum entering 2022. We remain on track for substantial annual revenue growth this year, and for the first time, expect to exceed $3 billion in annual revenue. This growth was demonstrated in our third quarter revenue results of $838 million, which represented a 39% growth over the same period last year. Our strong performance is underpinned by commercial execution, financial discipline, and strategic allocation of capital, as well as prioritization of commercial and R&D opportunities that have the most impact on our future growth. Launching multiple products over the past two years, coupled with the acquisition of GW Pharmaceuticals, has enabled us to significantly advance our objective of diversifying revenue. 52% of net product sales in the third quarter were generated from products which we have launched or acquired since 2019. Given our expectations regarding the durability and growth potential of these products, we remain confident in reaching our goal of at least 65% of net product sales coming from these newer products in 2022. Focusing specifically on the GW acquisition, we are demonstrating our ability to execute on the corporate development front. We successfully closed this transformative transaction in approximately 90 days post-signing, issuing over $5 billion of new debt with attractive and flexible terms to support the deal. The broad commercial and R&D portfolio we gained in the GW acquisition has accelerated our transformation, not only in terms of revenue diversification and R&D expansion, but also increased expectations for future top and bottom line growth. As Bruce mentioned earlier, we're very pleased with the progress of the GW integration. In bringing our companies together, not only have we enhanced our capabilities, expanded our footprint, and retained key talent across both organizations, but we are locking in our synergy targets and optimizing the way we operate and invest through transformation initiatives that are driving greater effectiveness and focus on our most important priorities. Since closing the transaction, our strong cash generation, driven by our continued financial and operational performance, has enabled us to achieve a 4.4 times net leverage ratio at the end of the third quarter. This represents a half-turn decrease in net leverage in just five months following the close of the transaction. Importantly, we're on track to achieve our stated net leverage targets of being below three and a half times by the end of 2022. In addition to reducing debt, we are also investing in our business to drive future growth and durability. This includes focused investments in the ongoing commercial launches of Zywaves, Zepselka, and Rylase, realizing the blockbuster potential of Epidiolex, and advancing our R&D pipeline and the GW cannabinoid platform. As our newly launched commercial portfolio matures and our business scales, we expect to realize further operating leverage and associated improvements in our underlying operating margins. Now turning to guidance, we are raising our full-year earnings guidance for non-GAAP adjusted net income, or ANI, to a range of $925 to $965 million dollars. up from our prior range of $830 to $910 million. Our updated non-GAAP ANI range exceeds the upper end of the prior range on both an absolute and a per share basis, which reflects both our financial discipline and strategic capital allocation. On the top line, we are narrowing our total revenue guidance range to $3.02 to $3.1 billion, from $3.02 to $3.18 billion. Reducing the midpoint of total revenue guidance reflects our updated oncology revenue expectations, which we have narrowed to $715 to $735 million, from $715 to $835 million. Our current oncology guidance reflects ongoing impacts of COVID on our legacy products and the RILES competitive landscape in the third quarter. We have also narrowed our neuroscience revenue guidance to $2.275 to $2.345 billion, while keeping the same midpoint as our previous guidance. On the expense side, we have reduced our total OPEX guidance by approximately $115 million at the midpoint, primarily to reflect the following three factors, one, a thoughtful approach to integrating the JAWS and GW operations. Two, prioritization of R&D activities to invest in those opportunities that we believe will deliver maximum value. And three, the extended duration of COVID-19, which pushed out a portion of our planned commercial spend for in-person interactions. I'll also note that included in our implied fourth quarter OPEX guidance is the launch of Zywave and IH, and three important clinical trial initiations with JZP385, JZP150, and Zepselka. The integration of Jazz and GW has been a catalyst for transforming our business. We are becoming a highly efficient and effective organization, poised to emerge as a nimble enterprise with the ability to scale rapidly, as we continue to increase our revenue diversification and growth. Our commercial portfolio now consists of multiple high-growth, long-lived medicines, which is complemented by an amplified R&D organization that is advancing multiple mid- and late-stage programs and a corporate development strategy with a track record of valuable contributions to our commercial and development efforts. We will continue to prioritize commercial, R&D, and business development efforts that drive value and growth, leveraging our strong cash generation to invest in our business, improve our bottom line, and continue to deliver strong shareholder returns. And now I'd like to turn the call back to Bruce.

Thanks, Renee. I'll conclude our prepared remarks on slide 19. Building on our current momentum, we expect to finish 2021 on strong footing, which will position us well going into 2022. With FDA approval of ZyWave for IH, we achieved our goal of five product launches in two years. Our commercial teams have demonstrated strong performance on the launches of ZyWave for narcolepsy and Zepselka, and we expect that successful execution will carry forward to the launches of Rylase and ZyWave for IH. The GW team orchestrated an excellent launch for Epidiolex, and its addition to our commercial portfolio provides us with the opportunity to deliver an important therapy to patients with refractory epilepsies. Our R&D organization continues to evolve and expand its capabilities. Trials for Nipiximols, JCP385, Rylase, and Zepzelka are now underway. and we are planning to initiate multiple mid and late stage clinical trials in the next 12 months. Our disciplined capital allocation has enabled us to expand our pipeline and diversify our revenues, and we are in a position to invest in those assets and opportunities that hold the highest potential to drive sustainable long-term growth and shareholder value. We have the ability to generate strong cash flow that allows us to make appropriate investments in our businesses while also achieving our deleveraging targets. That concludes our prepared remarks, and 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 at this time, please press star, then the number one key on your telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. As a reminder, please limit yourself to one question each. Thank you. Your first question comes from the line of Mark Goodman from SVP Learing. Your line is open.

Yes, hi, Rob. I heard that there's been some R&D activities that have kind of gone away. That's what Renee said. Can you talk about some of the programs that have stopped? I'm just kind of curious. There was GW had an autism program. They had a product for schizophrenia. They had a next generation program. epidiolex that they showed some early data on before the merger. Just curious, have those all been stopped, or just give us a sense of that. And then if you guys could just give us a little more color on RILAs and how to think about what's backlogged versus what's real demand and whether we should expect a massive step up this quarter. Thank you.

Renee, I'm not sure if you want to comment on what you were specifically referring to, but the way I would answer that question is, in coming together with GW, we've really had the opportunity to continue to invest in the highest value opportunities. And, of course, we've prioritized certain things, as we've described in this call tonight. There were many smaller studies that may have been investigated or initiated, or we've supported along the way, either on the GW or Jazz side, that may not ultimately progress in the pipeline. But I think, by and large, we've continued to invest heavily in all the key areas that we were investing in both prior legacy companies.

Go ahead, Renee.

Okay.

I was just going to add that this is also about, as we bring our organizations together, the how as much as the what. Certainly we've seen a lot of complementary skill sets coming from both areas. So in some cases, as we put together hiring plans and looked at the skill sets that we've needed, we've seen these two groups come together and offer more. versus what was originally anticipated. And that's not something that you'd have a really good idea of, Mark, until you get the groups together and really start integrating. We've also seen examples certainly of certain programs that would be duplicative across both pipelines. That's a great problem to have as you look at where to invest your capital to ensure that you're putting your capital behind your highest value activities.

Kim, maybe I can ask you to jump in on the Riley's question.

Sure. I'll start by saying that we've laid a really strong foundation and Riley's growth is continuing to accelerate. We've gotten initial feedback from our accounts that's very encouraging. We've received positive reports on the ease of both ordering and dose preparation as well as the JazzCare support services What I can say about ordering is that when Riley's was made commercially available in mid-July, there was still Erwin A's on the market on hand in hospital pharmacies that they were looking to utilize before placing orders. The temporary importation of UK Erwin A's from June, we saw a run out of stock in September. And that's where we really saw a notable uptick in Riley's orders beginning in September from customers. So overall, we're very encouraged by feedback from accounts, and we think we're in a strong place, you know, from an order standpoint.

Operator?

Your next question comes from the line of Jason Gerbery from Bank of America. Your line is open.

Oh, hey, guys. Thanks for taking my questions. So my eyes on ZyWave and thinking about the progression of the launch here, do you think there are accelerants to the rate of quarterly additions that are moving on to ZyWave? In your latest thoughts on HICMA, I think last quarter you framed it as a possible risk of market entry in 2022. Just curious if that's still the case. And ultimately, curious, Bruce, your comment about 4Q and providing an update there. I guess, what materially changes in the contracts that could allow you to talk about HICMA timing in February versus not being able to talk about it today in November? Thanks.

Yeah, maybe I'll take the back half of your question first, Jason, and then I can ask Tim to comment on Zywave progression. You know, what what will change in the fourth quarter earnings announcement is we'll be doing that in the context of giving full guidance for 2022 across our business, including neuroscience and including, uh, oxidate. And I think can give you a better sense of how we expect the year to, to play out. So it's not a, a comment specifically on contractual terms. It's just, you know, providing a full, uh, explanation of our expert expectations for oxidate, um, On the question of timing, nothing's changed since our disclosure of the last couple quarters, honestly, in terms of recognizing that although the contract says entry no later than January 1, 2023, there is a market decline provision that we believe could be tripped in 2022, but that's not different from what we've said before. On Zywave progression, I'll ask Kim to jump in, but, you know, we're really excited to have launched a product last week in a new indication. And so for the first time in our fourth quarter 2021 results, we'll, of course, have both narcolepsy and the beginnings of the IH launch. So that'll be a little bit of a change of just the trajectory we've seen thus far. Kim?

Sure. Great. So, you know, as Dan shared, you know, we're excited that ZyWave has achieved, you know, market-leading adoption in narcolepsy and that we've, you know, continued to see some nice solid growth through the third quarter. You know, we've seen to date very strong adoption among high-volume OXIV-8 prescribers and are now really increasing our focus on, you know, HCPs who have either not yet adopted ZyWave or have not transitioned yet the majority of their narcolepsy patients. You know, among those that have transitioned, most of their patients were focusing on, you know, oxibate-naive patients. While we anticipate that the adoption rates among these HCPs, and actually, you know, we've observed, you know, will be slower than we saw in the first three quarters, you know, we do remain focused on educating these HCPs and patients about, you know, the lifelong burden of high sodium intake. So we remain optimistic that HCPs will see the value in lower-sodium oxibate as we see the majority of, you know, oxibate-naive patients today being prescribed Zywaid as opposed to Zyrum. And, you know, we're very pleased that the FDA recognized the importance of lower-sodium options by granting Zywaid the orphan drug exclusivity back in June and went on to state that, you know, the clinical superiority findings were that ZyWave is clinically superior to Zyram by means of greater safety because ZyWave provides a greatly reduced chronic sodium burden compared to Zyram. And then, you know, the other driving factor, as Bruce just mentioned, of course, is that we launched ZyWave for the treatment of IH last week, which is the first and only FDA-approved treatment for adults with idiopathic hypersomnia. And we really see this launch as a significant step value driver with approximately 37,000 adult patients out there who've been diagnosed with IH and are actually out there actively seeking treatment for it in the healthcare system. So our commercial teams are working to educate right now about Zywa for IH while also, very importantly, continuing to educate about the importance of transitioning narcolepsy patients to Zywa due to the benefits of the lower sodium. Specifically in IH, we're focused on executing a very targeted launch strategy that includes both robust disease education and branded efforts. And to support this strategy, we have a variety of digital and in-person efforts that, you know, are helping to demonstrate both that IH is a unique medical condition and the clinical benefits and safety profile of ZyWave. So, you know, moving forward, we're going to be providing a number of metrics First, we'll continue to provide the average number of OxyBait patients. We'll continue to provide the total number of patients on ZyWave, and we will start to provide the breakdown of the number of ZyWave patients based on diagnosis of either narcolepsy or IH.

Got it. Thank you.

Your next question comes from the line of Jessica Faye from J.P. Morgan. Your line is open.

Hey, guys. Good evening. Thanks for taking my question. Renee, you talked about how as the newly launched commercial portfolio matures and scales that you expect to realize further operating leverage. Can you talk about if we should expect operating margin improvement in 2022 over 2021? Yeah, thanks for the question, Jess. So, I would say

Stay tuned for 2022 guidance. As Bruce mentioned, we'll plan on giving that specific guidance in early 2022 when we're reporting our year-end results. And that would be more appropriate after we've gone through our full budget and goals process with our board of directors. But beyond that, I would think more broadly about, yes, as our newer products then start to mature, into products that have gotten through that initial launch phase that are off to a strong start that you should expect over time that operating margin, whether it be specific to SG&A or as we're thinking about our broader cost structure to improve.

Okay, got it. Yeah, I'm just trying to figure out if next year counts as one of the years of those launch products beginning to mature or still kind of more of an investment year.

Yeah, Jess, what I would say is... Go ahead, Renee.

Yeah, I'd say without giving specific guidance on what that would look like, we'll be focused on ensuring that in 2022, we're positioned to achieve our goal of having 65% of our revenues associated with those newer products, that being ZyWave, Epidiolex, Zepzelka, Rylase, And as you think about where our focus is, it's making sure the long-term growth is positioning us to be able to achieve those operating margins. Of course, with the transaction, we did say that we expected accretion in the first full year. And we've also talked a lot about investing in our pipelines. So while we're going to be focused on improving our bottom line margins, we're also going to be focused on ensuring that we're putting sufficient investment behind our R&D portfolio and pipeline to ensure that we're creating greater strength and greater durability. Thank you.

Your next question comes from the line of Jeff Hung from Morgan Stanley. Your line is open.

Thanks for taking the question. You mentioned high persistency for the Epidiolex indications. I guess from here on out, which of the indications do you see as the bigger potential drivers for Epidiolex sales, and what kind of impact do you expect going forward potentially from off-label indications? Thanks.

Dan or Kim, you want to jump in on Epidiolex?

Yeah, I'm happy to start, and then, Kim, you can add in. But as I mentioned in the earnings call, We anticipate, especially as the COVID-19 pressures ease and based on the real-world experiences that we've had with the physicians who have adopted the therapy, that there's plenty of room for patient growth across all three of our indications. And kind of more broadly, there's this pool of treatment-resistant epilepsy patients, 160,000 pediatric and a million overall patients. Many of them are with syndromes that have no FDA-approved therapies, and so often the physicians are looking at the seizure types for those disorders, and given that Epidiolex has a broad range of activity across multiple seizure types and good market access to support physicians and patients in those settings, like most anti-epilepsy drugs, we do think that Epidiolex will become a cornerstone of therapy across multiple seizure types beyond the indicated label. Kim, I don't know if you want to add anything.

No, I think you covered all the points well, Dan.

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

Good evening. Thanks for taking the question. Just more on Epidiolex, can you give us some more color on where you are with the patent application? You indicated that you expected to be initiated, sorry, to be issued by the end of the year. So maybe any more color there. And then just with regards to the myotronic atonic seizures, why did you pick that? What was the basis on which you thought that there was applicability in that seizure type. And if you could give us some preliminary sense of what is the target market potential if it works in that seizure type. Thanks.

Yeah, Ami, nothing more to add on the timing of the new patent issuance and Orange Book listing. And I'm not sure the timing of that is particularly important other than obviously what the long-dated expiration of that patent would be. Rob, maybe you could talk a little bit about why we've elected to go into the EMOS trial next, and then Kim or Dan, you can talk about potential in that marketplace as well. Rob?

Yeah, happy to, Bruce. So, you know, first of all, it's an important non-medical need in EMOS amongst pediatric epilepsies. And based on prior data and other Seizure disorders, we think there's a high probability of it working in that setting. So there'll be a direct benefit to those patients. We also think it adds just evidence of broad anti-epileptic activity of Epidiolex by studying a syndrome that is known to have a seizure type that is different than we currently have an indication for. So it'll complement the seizure types that we've already addressed in our indications. And as you know, doctors treat seizure types. They don't necessarily treat the underlying disorder as part of the epileptic therapies. And so it provides that additional data on broad activity across seizure types. And, you know, while we wouldn't promote off-label, these are the kinds of data that physicians often look for to provide evidence of efficacy in the patients that they're intending to treat.

Yeah, and just jumping in there, you know, EMOS represents approximately 2% of childhood epilepsies, so not an insignificant disorder. But, you know, even more importantly, it rounds out our data set, which includes, you know, strong activity and combinability and safety and tonic, atonic, and now myoclonic and clonic seizure types. So it's just, you know, painting the broad picture evidence generation across multiple seizure types that are typically seen in this treatment-resistant epilepsy population. So that, along with other studies we're considering and investigator-sponsored studies, both looking at disorders, safety efficacy endpoints, and other endpoints where we see benefit beyond seizure type or seizure reduction is part of our overall evidence plan.

Thank you.

Your next question comes from the line of Gary Nackman from BMO Capital. Your line is open.

Hi, good afternoon. Could you talk about the overall reimbursement and access for ZioWave? How the net pricing has been trending for the narcolepsy indication? What the initial status has been for IH? How you've been managing that? And then what might change when an AG of Xyrem is available next year? How much visibility do you have on that at this point? And then just one other one, if I could sneak it in. Just on Synosy, there was a big acceleration, it seemed, in the third quarter. So you didn't comment on that in the prepared remarks. How much of that is net pricing versus actual demand volume? Thanks.

Kim, maybe you could address both those ZyWave payer dynamics now and going forward, as well as Sanosi progress in the third quarter.

Sure. Yep. So with ZyWave, you know, we're very pleased that we continue to have greater than 80% commercial coverage for patients, you know, in narcolepsy. And this really sets us up well for IH. I think we've said and we continue to see You know, with the launch of IH, really what we are looking to do is see payers add basically utilization management criteria to the existing contract and coverage, you know, for ZyWave and that criteria being specific to patients with IH. You know, in the meantime, and we're anticipating that that will happen as fast, if not faster than it did, with the launch of narcolepsy, where our goal was, and we saw us achieve broad coverage within six to nine months or so of launch. In the meantime, many patients can pursue the medical exception process and get coverage there. And then lastly, where that doesn't work, we do have patient access and support programs available for those patients. starting with day one of launch. I think your next question perhaps was about what might change in terms of the AG and our coverage situation. We feel quite confident that we will continue to enjoy strong coverage based on our conversations with payers in this space. We don't anticipate for them to really change the coverage and ultimately to put down the AG side-by-side, you know, with Xyrem specifically on their formulary not advantaging or disadvantaging in any way.

And then, Kim, maybe just a comment on what we saw in Sanosi in the third quarter.

Yeah, sure. You know, so in the third quarter, we saw that, you know, Sanosi sales more than doubled compared to the same period last year, and we saw prescriptions specifically, you know, increased by 8% in third quarter over the second quarter. So, you know, since launch, we've seen very encouraging reactions to the profile of Synose from both our physicians and our patients, and we continue to receive positive feedback from those who have actually utilized the product. You know, patients have a really good experience on Synose, In terms of what they're seeing is the impact on their excessive daytime sleepiness. And, you know, these are patients who have often been quite frustrated that they've rotated through other weight-promoting agents and stimulants over time. I don't have the breakdown of that growth as to what was demand and what was price. I don't know, Renee, if you have that or not.

Yeah, I don't have that in front of me, but certainly we saw gross-to-net stabilize a few quarters after launch as we finalized our broad access. So what you're seeing now almost exclusively represents volume growth.

Okay, great. Thank you.

Your next question comes from the line of Akash Tiwari from Jeffrey. Your line is open.

Hey, guys. And I apologize for this question being a bit on the nose, but what is the current market penetration for Epidiolex and Dravet, LGS, TSC, and other refractory epilepsies? And then maybe on guidance, it looks like full-year guidance was lowered, $70 million for SG&A, R&D about $45 million. And you talked about kind of three different reasons for that. How much of the OPEX decrease was spend that was supposed to occur in 2021 going to 2022 given COVID-19? And how much of that was GW integration and R&D prioritization? Can we expect a more 4Q-like cost basis going forward into next year or not? Thank you.

So Dan or Kim, maybe I'll ask you to talk a little bit about use in our existing indications and where we are there in terms of room for growth. And then, Renee, perhaps I can ask you to weigh in on the cost side.

Yeah, I mean, sure. What I'll basically say is that we're, you know, pleased with the penetration rates we're seeing. I don't think we share the specific, you know, data on that. But, you know, what we see is that there is you know, substantial room for growth, particularly in LGS and our newest indication around TSD. So we remain very encouraged in terms of, you know, the growth opportunity for this product across the indications.

Yeah, and maybe I'll just add, and while there's, you know, some use outside of those disorders, there's clearly a lot of, it's a very small penetration into that treatment-resistant patient population, whether it's the pediatric population of 160,000 or the million overall. So, again, I think the real-world experience plus data set will continue to support strong growth going forward.

Do we know what percent of sales is in the other refractory epilepsies as a percent of total sales for epidiolex right now?

Yeah, we're not providing that level of detail at this point.

And I'm happy to jump in then on OpEx. So really, the categories, of course, that I provided are where we're seeing the biggest part of the shift in OpEx. We're trying to be very thoughtful about how we integrate Jazz and GW, much of which has already been completed. And as we've prioritized some of these activities, be it on the commercial side or R&D activities, it's really focused on Where are we going to get the maximum value? When we initially provided our guidance and rolled that forward in the prior call, we were continuing to learn how the operations were coming together, continuing to figure out what we needed to invest appropriately behind our combined pipeline and our commercialization activities. And we're also looking at how we should operate moving forward as a larger combined company and how to be more effective and efficient as we prepare ourselves to scale with our increased revenue growth over time. So that's largely how I would encourage you to think about the way that we've brought down the expenses. And then I would also say with respect to the implied Q4 numbers, I wouldn't immediately apply those to our future rates. As I mentioned earlier, we'll provide specific guidance for 2022 as we report out our year-end earnings in early 2021. And then I would also just remind you, we stated in our prepared remarks, That in Q4 we're launching IH. We're also initiating multiple clinical studies, sorry, clinical studies in the quarter. And so there is some expense that's associated with taking on initiation and getting those underway. Okay.

As a reminder, please limit yourself to one question each. Thank you. Your next question comes from the line of Umar Rafat from Evercore. Your line is open. Umar, are you there? Umar Rafat from Evercore, your line is open. Your next question comes from the line of Balaji Prasad from Barclays. Your line is open.

Hi, good afternoon. Thanks for the questions. I just want to discuss epidemics a bit further. While I understand that you had limitations on accessing pediatricians, the data point and interactions going down you gave is quite insightful. What I'm struggling to understand is the lack of vaccine and how that's impacting on the ground. I'm surprised that parents with kids suffering from epileptic conditions are not accessing or getting the treatment needed. Maybe some qualitative or quantitative comments on it. And secondly, maybe just on the individual markets, do you have a better understanding of the current market size of Lennox-Gastaut or Dravet syndrome currently? What's the number of patients out there and penetrations if you have? Thank you.

Yeah, on the first part of the question, maybe I'll just jump in and talk a little bit about what I've heard from parents and treaters during this period, which is parents of kids with these refractory seizure disorders are very interested in getting to better seizure control and, you know, better overall health status of their child, but they can be worried that in the process of changing meds, you can disrupt in a way that can actually bring on additional seizures during that change, and those additional seizures can, in some cases, result in needing to visit a hospital, and so we think based on conversations, again, with both parents as well as treaters, that there's been a tendency to avoid making those changes for fear of having to go into a medical environment and risk COVID with unvaccinated kids during this period. We don't think that's unique to Epidiolex as a product. We think that's more general for these treaters and these conditions generally.

Your next question comes from the line of Esther Rajavello from UDS. Your line is open.

Hey, thanks for giving me the question. I'm going to add to the list of epidiolex questions here. I guess for the OUS market, can you share any early feedback from prescribers and families? I'm basically trying to get a sense for pent-up demand in the developed EU markets. And then in the U.S. among DRAVE patients, can you share whether any of the newer drugs like Fentepla are used in combination with Epidiolex? And then lastly, can you give us some color on the proportion of the GW sales force that continues to be employed by JAV and whether you've had to expand hiring efforts in the U.S. for this product?

Yeah, I was just going to jump in on the ex-U.S. and then leave the other question. But on the ex-U.S. side, we've got a strong team, much like we had in the U.S. that GW had built up in the major market countries. And importantly, the gating factor, of course, is getting favorable reimbursement. And we've now achieved that in four of the five major countries. And that really opens the gate to full promotion and rollout. And, you know, in the fall, we've got the additional sort of growth going on with the two markets that most recently got that reimbursement, which were Italy and Spain. We're very targeted now on the fifth remaining country, which is France, which could be a very significant growth market for us. And that one we anticipate to be launching into in 2022. I think relative to other sort of orphan-priced branded products, to have overall pricing in these major countries at greater than 70% of the wholesale acquisition cost in the U.S. is very successful, and it really speaks to both the market need, the product profile, and the data that's been generated. You know, we look forward to further updates, but that definitely was a big part of our, you know, evaluation of Epidiolex was the worldwide potential for this important new therapy.

And then I'll jump in on the last part of your question. Operator, I think we're not quite done. So on the sales force, you know, the North American business unit within GW, the Greenwich team, was brought over in its entirety to Jazz. So no, there's been no reduction in that effort. Again, we're trying to build on the success that GW is having and move forward together. On the question about combination use with Pentepla, I would say in general we see combination use of products for these conditions We hear good feedback about combination of epidiolex with other agents in terms of its side effect profile, in terms of ease of initiation of adding epidiolex in. We hear that when patients are rotating off therapies, they often preferentially continue on epidiolex. So I'm not sure I have lots of quantitative evidence data on Fintepla specifically at this point, but I'd say what we hear about use of Epidiolex in general seems to be what we're hearing here as well.

Yeah, Bruce, I'll just throw in a couple proof points. I know Dan shared earlier that what we're seeing in market research is that about 40% of respondents indicate they are moving Epidiolex up in their treatment algorithm. So we see that as a very good signal I believe it's, you know, underpinned by more prescribers having, you know, positive experience with Epidiolex over time and gaining experience with the product. And then the other point is just we see very strong persistence with the product. Once patients go on this product, you know, they stay on it for a really long time. So I think both of those, you know, are data points that point to, you know, levels of satisfaction out there in the market on the part of both prescribers and patients.

Your next question comes from the line of Ronnie Gal from Bernstein. Your line is open.

Good afternoon, and thank you for taking my question. Just about royalized You know, the peak for the Airways market was around $200 million. It kind of came down to around $170 during the year when there was not enough supply. And I was kind of wondering, as you now have more information with the Rylers launch, where do you see the end of the initial ramp-up where you simply replaced Airways and versus where you'll have to start building the demand further with some marketing? Just kind of help us out. look at the shape of that product for the next couple of years.

Yeah, Dan, maybe I could ask you to jump in on just the overall market opportunity with Riley's moving forward, both U.S. and ex-U.S. as well.

Yeah, no, it's a good question, Ronnie, and I think we don't quite know how big the market could become because, as you know, as we ran into those supply constraints, you know, more than five years ago, we pulled back all promotional efforts, all medical education initiatives, and we had to put in fairly strict ordering policies where it was on a, you know, patient by patient basis. And, you know, institutions really had to triage which patients got the therapy. So I think in addition to, you know, growing back the market fully, There's also the retraining of physicians and, you know, caregivers having the opportunity that at the slightest hypersensitivity reaction, you don't continue to reach challenges they may have during shortages and sort of risk anaphylactic shock, but you give the opportunity to switch more quickly to a non-E. coli-based asparaginase. You know, and importantly with Rylase, given that we had a year's supply at the time of launch and very robust Supply chain, the institutions and COG who worked with us on the study have great confidence that they can look for silane inactivation, look for that hypersensitivity reaction, and really grow the market. We said in addition to that, there's an opportunity to go more fully into adolescent, young adult, which could be sizable, and there's more drug use there because it's on a per-weight basis, and then there's geographies like Japan that have an unmet need where the product never got introduced because of supply and quality issues, and Rylase is in a very different situation. So I look forward to giving further color to exactly what that potential could be, but we do see it as a growth driver for our immediate future.

Your next question comes from the line of Brandon Foulkes from Cantor Fitzgerald. Your line is open.

Hi, thanks for taking my question. I just want to circle back to ZyWave. The goal of having more than 50% of patients on ZyWave by 2023, you seem to be well on your way there, but Maybe can you just talk about how dependent achieving that goal is on IH from here? Thank you.

Yeah, maybe I'll jump in on that one and just say, you know, we picked a date a little farther out in this metric of 2023 because we specifically wanted to address what we think would happen to ZyWave even in the face of competition from a generic or branded higher sodium product. So it wasn't so much just a continuation of the existing trend and where we'd get to, but where we'd still be after a potential other entrance to the marketplace. So hopefully that makes that metric a little bit clearer to you. You know, we do see a very significant opportunity in idiopathic hypersomnia with no indicated treatments prior to our launch last week of ZyWave. patients who really need effective therapy to treat excessive daytime sleepiness, but symptoms even beyond that. NIH, you know, this is a new launch. No product has been promoted in this space before, so we do have some education to do. It's also a little unlike ZyWave in narcolepsy, where many of our ZyWave patients were coming over already titrated up and on a effective dose of Xyrem and then moved over dose for dose, you know, obviously a naive IH patients coming on would be titrated up on dose over time. So a little bit different dynamic in terms of uptake, but we certainly see that as a significant opportunity potentially over time, you know, rivaling the size of narcolepsy in terms of potential overall patient's with better diagnosis and treatment. We're not predicting that in the near term, but certainly that opportunity is there for a really substantial improvement for a number of patients with IH.

Your next question comes from the line of David Amsellon from Piper Sandler. Your line is open.

Thanks. On Epidiolex, with the the clear evidence of some off-label use beyond the three indications in the U.S. label. I was wondering if I could get your thoughts on payer contracting and just trying to get more aggressive with payers such that you could facilitate less in the way of utilization management. How do you think about that? And then I'm sorry if I missed this, but are you disclosing or did you disclose the XUS contribution from Epidiolex during the quarter? If you can disclose that, that would be helpful too. Thanks.

Yeah, David, I'll take the second half of your question and say I don't think we've provided a specific U.S. versus XUS breakdown product by product, but we're really excited about how the Epidiolex launch continues to roll out. in Europe across markets, both in terms of pricing and access we're receiving, but also how our teams are performing in the early periods of these launches, and see this as a really significant opportunity relative to the U.S. over time. On payer coverage and what that means in terms of utilization of the product, Kim, could I ask you to weigh in on that?

Yes. Sure. So right now we're very pleased that Epidiolex enjoys 98% commercial coverage across commercial lives. And, yes, as you suggest, we do see it as a strategic priority, and we are focused on trying to broaden that coverage. And so that coverage is in the indicated lives that we have. We are working with payers to try to broaden that coverage And we've been very successful on that front in the Medicaid space and are continuing to try to get there in the commercial space.

Your next question comes from the line of Ken Cashator from Cohen & Company. Your line is open.

Hey, Bruce and team. Sorry I'm really late getting on the call, but I wanted to go back and ask about your reference to the Epidiole's composition of matter-like patents. Can you get into a little bit of nuance on these patents, more in the specificity of them, with this being worked on for a while at GW, part of your original diligence, and you were aware of them, something that maybe you helped them with. Can you give a little more specificity around them? Thank you.

Yeah, Ken, this is something we were aware GW was working on. I think GW did make reference to it publicly on a couple of occasions. We're getting more specific now just about timing. I think we'll wait to say more until that patent is visible to everyone and we can talk about it more specifically. I don't think it makes sense to do so right now, but obviously what we're trying to communicate is that the IP continues to broaden and that it has different pieces to it and can have different expiration dates, in this case, out to 2039. So more to come when we have more in the public domain, but just wanted to make sure people are focused both on the near-term opportunity for Epidiolex in the U.S., in the ex-U.S. launch that's on their way, in potential new indications, in broader use, but also in recognize that we view this as a very durable asset.

Your next question comes from the line of Greg Frazier from True Risk Securities. Your line is open.

Good afternoon, folks, and thanks for taking the questions. What percentage of new-to-Oxibate patients are being prescribed Zywave versus Zyrem? You mentioned a large majority, but can you be more specific? And what are the reasons that you hear as to why Oxibate-naive patients are still prescribed Zyrem? Is it access-related? Physicians just aren't aware of Zywave yet? Any color on that would be helpful. Thanks.

Yeah, Greg, I particularly like the end of that question. That's always a good question when you've got a better therapy, a superior therapy available. Kim, you want to talk a little bit about oxidate naive patients and what we're seeing and what might be driving that?

Yes. So, a couple of reasons. So, one is that, you know, while we have very strong commercial coverage, over 80% in commercial patients, there is still a portion of patients that don't have immediate access to Xyrem. So, that's one of the reasons. But really, the biggest reason out there right now is that healthcare, you know, Xyrem is a Patients love their Xyrem and HCPs love Xyrem. And so the number one reason we're hearing is that, I'm sorry, that's on the transitions that patients are satisfied with Xyrem. But we still have some work to do, as I said before, with some segments of physicians. and really motivating them, you know, to adopt ZyWave based on the low sodium. But we feel very confident that we're making strong progress there and that these, you know, smaller segments of HCPs will eventually, you know, move along that continuum and, you know, join the rest of the, you know, high-volume oxibate prescribers who really do see the benefits of, you know, going with a product that lowers that sodium burden.

Your next question comes from the line of Annabelle Samimi from Stifel. Your line is open.

Annabelle, are you there?

Annabelle Samimi from Stifel. Your line is open. Your next question comes from the line of Navan Tee from Citi. Your line is open.

Hi, good afternoon. First, a follow-up on the lower than expected SG&E and R&D. Are you able to tell us which products will be impacted by the lower selling and R&D expenses or which will be prioritized? And then my second question is on your latest thoughts on the litigation versus Avadel FT218 after the action date was delayed. Thank you.

Yeah, I'll take the second part of your question first and just say nothing additional to say on litigation ongoing with around FT218. Obviously, we have existing IP, which you've seen more of over time, and we'll defend that IP as we see fit. On the expense side, what we were lowering here was guidance for the full year in terms of overall spending across two organizations that just came together a few months ago, as well as our expectations, you know, in particular as we have more visibility late in the year. Renee, I'll let you weigh in on what else you want to disclose there.

Yeah, actually, I think you've covered it. And I think just to address the specific question in terms of how does this look by product, If you think about the commercial side, obviously we have multiple product launches we've been moving forward, and the impacts of COVID and that lack of in-person interaction that many companies had expected to grow in Q3 and Q4 has been impacted by COVID. So it's not specific to one product necessarily other than in thinking about where we're really putting our commercialization dollars right now. And that is to support the new product launches that we've talked about representing the 65% of revenues that we expect in 2022 from those products that have been launched or acquired since 2019. So ZyWave, Epidiolex, Apselka, Rylase, and Synosy.

This concludes our question and answer session. I would now like to turn the conference back to Mr. Bruce Kozad for the closing remarks.

Yeah, thanks, Operator, and thanks to all of you for the good questions. You know, I'll just say we're really happy with where we are this year in terms of kicking off our fifth launch, continuing progress early in the launches of Rileys and continuing to progress Zepselka. You know, a flurry of activity at the end of the year, initiating some mid- and late-stage trials we're really excited about. You know, you saw our delevering in the first five months, a half-turn, which I think is really excellent progress. And then the ability to bring more of this to the bottom line as we operate as a combined more agile company. So really excited about where we're headed and, you know, what's in front of us for 2022. We look forward to speaking with many of you at the upcoming Jefferies London and Evercore investor conferences. And I'd just like to recognize all our jazz colleagues for their efforts, which are, have led to delivering these new therapeutic options to patients, and to thank our partners and shareholders for their continued confidence and support, and thank everyone for joining us today. Stay well, everyone.

Ladies and gentlemen, this concludes today's conference. Thank you for your participation, and have a wonderful day. You may all disconnect.