Jazz Pharmaceuticals plc

Good day and thank you for standing by. Welcome to the second 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 during the session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Andrea Flynn. Please go ahead.

Thank you, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its second 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 Galla, Executive Vice President and Chief Financial Officer, Dan Swisher, President, and Rod Yannone, Executive Vice President, R&D, and Chief Medical Officer. Hill Jockelson, Neuroscience Therapeutic Head, will also join the team for Q&A. On slide two, I'd like to remind you that today's webcast includes forward-looking statements, such as those related to our future financial and operating results, growth potential, and anticipated development and commercialization milestones and goals, which involve risks and uncertainties that could cause actual events, performance, and results to differ materially from those contained in these forward-looking statements. We encourage you to review the statements contained in today's press release on slide two 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 slide presentation available on the Investors section of our website. With that, 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. Looking back at the first half of the year, I'm proud of how our team has continued to deliver operational excellence. We accomplished milestones across commercial, R&D, and corporate development that collectively are driving our transformation to an innovative, high-growth global biopharma company. Our recent acquisition of GW Pharmaceuticals, combined with progress across our existing business, is foundational to what we expect will be a period of sustained growth for Jazz, underpinned by our ability to deliver on our expanding pipeline and our corporate development activities, as well as by leveraging our substantial commercial prowess and enhanced global footprint. We continue to be impressed with the superb cultural fit between legacy Jazz and GW teams and the successful completion of our integration will only further enhance our ability to innovate and execute. We are on track for another year of strong financial performance and sequential revenue growth. And for the first time, we expect to exceed $3 billion in annual revenue. I also want to emphasize the makeup of this revenue. Several years ago, we made revenue diversification a key corporate objective. With 41% of net product sales in the second quarter from products launched or acquired since 2019, we are well positioned to reach our goal of at least 65% of net product sales from these newer products in 2022. And these newer products are not only innovative therapies that address critical needs for patients with neurologic disorders and cancer, They are also durable assets with high growth potential. In short, Jazz has never been stronger. It's particularly striking that we've been able to consistently execute at such a high level while navigating the challenges created by the global pandemic. This was only possible thanks to the dedication and engagement of our teams across Jazz. We are taking the lessons we learned about remote work and collaboration over the past 18 months to redefine the future of work at Jazz. We believe that the combination of a purpose-focused culture that delivers innovative therapies to patients, the opportunity for rewarding professional experiences, and a workplace that adapts to meet employee expectations regarding flexibility, collaboration, diversity, and inclusion will make Jazz an even more attractive place to work for both our existing teams and top talent across our industry. I'm not going to address every bullet on slide five, as Dan, Rob, and Renee will provide greater detail, but I do want to note a few items that are key drivers of our future growth. We successfully closed the GW acquisition in early May, which has strengthened our position as a neuroscience leader with a global commercial and operational footprint. The acquisition is highly complementary to our existing business, further diversifying the commercial products we deliver to patients and adding the exciting GW cannabinoid platform to our R&D portfolio. We have also gained numerous talented colleagues and integration remains a key focus. I'm pleased with our progress today and we have successfully retained many GW employees who are in roles that are crucial to our continued success. The GW acquisition was transformative for our business and we are excited about the long-term value we believe it will deliver. We are very pleased with strong ZyWave adoption in the second quarter and that the benefits of a lower sodium oxibate are resonating with physicians and patients. It is our view that ZyWave as the only lower sodium oxibate product will be the oxibate therapy of choice even after other higher sodium oxibate products are available. We continue to expect that a majority of OxyVe patients, across all approved indications, will benefit from ZyWave in 2023. Looking ahead, we are preparing for the commercial launch of ZyWave in idiopathic hypersomnia, or IH, later this year pending FDA approval. This would be our fifth product launch since the beginning of 2020, achieving a key company objective while delivering a new treatment option to patients with IH. This hypersomnolence disorder has a profound effect on multiple aspects of daily life, and there currently are no approved therapies to treat IH. Turning to Zepzelka, we saw strong underlying growth in demand in second-line treatment as we moved toward our goal of establishing Zepzelka as standard of care in that setting. Zepzelka is providing an important therapeutic option for patients with small cell lung cancer, and we are advancing a robust development plan for this therapy, including initiating a phase three trial this year in combination with immunotherapy in first-line small cell lung cancer. And continuing with our oncology portfolio, on June 30th, we were pleased to announce FDA approval of Rylase, previously referred to as JZP458, under FDA's real-time oncology review. Rylase became commercially available on July 15th. This is a critical therapy for patients with acute lymphoblastic leukemia and lymphoblastic lymphoma who have developed hypersensitivity to E. coli-derived asparaginase, and we are excited to deliver a high-quality therapeutic option with reliable supply to these patients. Together with ZyWave, RyeLase showcases our growing R&D capabilities and demonstrates our ability to bring medicines from concept to commercialization. I'll now turn the call over to Dan for an overview of our commercial performance, after which Rob will provide an update on progress across our R&D programs. Rene will close our prepared remarks with a financial overview, and then we'll open the call to Q&A. Dan?

Thanks, Bruce. I'm excited to share the progress across our commercial portfolio. I'm going to begin with the neuroscience on slide seven. starting with our combined Oxibate franchise, including Zyrum and Zywave. Net product sales for the Oxibate franchise were $458.3 million, 3% higher than the same period in 2020. Average active Oxibate patients increased to approximately 15,900 in the quarter, an approximate 5% increase over the same period last year. The strong adoption of Zywave continued through the second quarter, with net product sales of 124.2 million. We exited the quarter with approximately 5,100 active ZyWave patients, up from approximately 3,900 at the end of the first quarter. We remain focused on educating physicians and patients about the lifelong burden of high sodium intake, particularly in a patient population with an increased risk of cardiovascular comorbidities. and that ZyWave is designed to enable patients to address this modifiable risk factor. This messaging is resonating with healthcare professionals and patients. In the first three quarters since launch, we have been successful at educating both high volume Zyrum prescribers and current Zyrum patients to facilitate their adoption of ZyWave. We are increasing our focus on healthcare providers who have either not yet adopted ZyWave or who have not transitioned the majority of their narcolepsy patients, as well as to oxybate-naive patients. While we anticipate that adoption rates will be slower in these groups compared to early adopters, we continue to make steady progress in expanding the prescriber base, and we've seen a continued preference for ZyWave over Zyrum among oxybate-naive patients. We see a significant opportunity to continue to grow ZyWave in narcolepsy, and as Bruce noted, we are also planning for a fourth quarter commercial launch of ZyWave in idiopathic hypersomnia, or IH, pending FDA approval and following REMS implementation. If approved for this additional indication, ZyWave would be the first and only therapy indicated to treat IH. So as a reminder, the first Xyrem-authorized generic, or AG, can enter the market on January 1, 2023, or earlier if triggered by a significant decline in Xyrem revenue. While we do not anticipate that this Xyrem market acceleration clause will occur in 2021, given the strength of ZyWave adoption, it could occur earlier than January 1, 2023. This would be a real mark of the success of the ZyWave launch. We do have meaningful royalties on net sales of the AG products with the royalty rate increasing during the initial AG term based on increased AG sales. I should note that generic Xyrem will only be approved in narcolepsy as there is no data for Xyrem in IH. Next, we're exceptionally pleased to add Epidiolex to our neuroscience portfolio. with the close of the GW Pharma acquisition in May. The GW team has done a fantastic job in the launch of this product in both the U.S. and more recently in Europe, and the growth we've seen this quarter was in line with our expectations. We view Epidiolex as a durable product with near-term blockbuster potential that addresses a significant unmet need to treat childhood-onset treatment-resistant epilepsies. In our press release today, we announced that we are planning to initiate a pivotal phase three trial of Epidiolex for the treatment of epilepsy with myoclonic atonic seizures, or EMAS, also known as DOSA syndrome. This trial will expand the evaluation of Epidiolex in treating a broad range of seizure disorders. Rob will cover this trial in more detail shortly. We continue to see Epidiolex growth coming from current indications of Dravet, Lennox-Gastaut, and TSC, as well as potential future indications such as EMAS. Epidiolex has broad access to date in the U.S. with more than 97% of all lives covered, and there is a high persistency rate for patients who initiate therapy. In the second quarter, Jazz recorded net product sales of $109.5 million for Epidiolex. This represents revenue from the close of the GW transaction on May 5th through the end of the quarter. On an unaudited pro forma basis, full second quarter net product sales were $155.9 million, a 32% increase over the same quarter of 2020. As COVID restrictions ease in the U.S., we are seeing an upturn in patients visiting their physicians, which we believe will drive additional growth of Epidiolex with new patient starts. In addition, the European launch is progressing well, with favorable pricing and access to date and reimbursement in place in four of the five largest markets. Moving to Synose, second quarter net product sales were 12.1 million, a 41% increase over the same period last year. Our expanded and dedicated Synose sales force has now had a full quarter in the field, Synosy is highly promotionally sensitive, and we believe that greater access to clinics and physicians will benefit the brand. We are also continuing to make strides in our rolling European launch of Synosy, including securing reimbursement in the key market of Germany. So now I'm going to turn to the oncology portfolio on slide 8. We continue to see strong growth in demand for Zepzelka, with net product sales of 55.9 million in the second quarter of 2021. Growth in the second-line share and overall demand continues to increase in line with our expectations, with sequential demand growth over the last two quarters of 8% and 9%, respectively. While we continue to have strong underlying growth, I will note that there was lower sequential growth rate in net sales over the first two quarters of 2021. This was mainly the result of reduced inventory holdings by distributors in this early launch period. We expect that as distributors gain more experience with customer demand levels, our growth in net sales will be more closely aligned with overall demand in future quarters. As Bruce mentioned, ZEBZOCA is providing an important therapeutic option for patients with small cell lung cancer, and we're making progress toward our goal of establishing ZEBZOCA as standard of care in the second line setting. Turning to asparaginase, second quarter IRWIN ACE net product sales were 28.3 million. As previously disclosed, we distributed our remaining supply of IRWIN ACE in the second quarter and we have discontinued selling this product. We're very excited that our internally developed recombinant erwinia asparaginase therapy, or Rylase, was approved at the end of June and is now commercially available. Rob will discuss Rylase in more detail shortly. Vixios net product sales in the second quarter were 31.5 million, an increase of 18% compared to the same period in 2020. We continue to support the growth of Vixios with ongoing development and commercial activities, as well as expansion into new international markets. We were pleased to gain the recent approval from Health Canada in early July. For Defitilio, we saw second quarter net product sales of 48.1 million. This was an increase of 13% over the same period last year. So in summary, we remain focused on strong commercial execution across our neuroscience and oncology portfolios. We're excited about the opportunities in front of us, including the launch of Rylase, the anticipated launch of ZyWave and IH, the continued rollout of ZyWave and narcolepsy, the growth and development of ZebZelka, and working with our new colleagues from GW Pharma to maximize the opportunity of Epidiolex and realize its blockbuster potential. I'm now going to turn the call over to Rob for an update on our development programs. Rob?

Thanks, Dan. I'll start on slide 10 with an important milestone for ZyWave. FDA recently granted orphan drug exclusivity for ZyWave and narcolepsy. In connection with this, FDA also published its summary of clinical superiority findings for ZyWave for the treatment of cataplexy or excessive daytime sleepiness in patients seven years of age and older with narcolepsy by means of greater safety compared to Xyrem. FDA noted that, quote, ZyWave is clinically superior to Xyrem by means of greater safety because ZyWave provides a greater reduced chronic sodium burden compared to Xyrem. And also stated, quote, The differences in the sodium content of the two products at the recommended doses will be clinically meaningful in reducing cardiovascular morbidity in a substantial proportion of patients for whom the drug is indicated. We are encouraged that FDA recognize the benefits of reducing sodium in a chronic medication for narcolepsy patients and believe FDA summary will be meaningful to both physicians and patients. Now turning to our neuroscience development program on slide 11, I'll continue with ZyWave to highlight that we are less than two weeks away from our August 12th PDUFA action date for our supplemental NDA filing with FDA for idiopathic hypersomnia. Progressing as expected, and we're excited about the potential for whom there are currently no approved therapies. Looking at other opportunities in our neuroscience pipeline, I'm very pleased to report that the integration between our JAWS and GW R&D teams is progressing well, and the combined organization is collaborating to advance multiple therapies across our neuroscience portfolio, including a number of programs emerging from the GW cannabinoid platform. Epidiolex is currently approved in three refractory seizure disorders, and we expect to initiate a registrational trial in a fourth, epilepsy with myoclonic atonic seizures, or EMOS, in the first half of 2022. Patients diagnosed with EMOS, which is also known as Doza syndrome, experience generalized myoclonic atonic seizures. The onset of EMOS occurs commonly in the first five years of life, with the mean age of onset being three years. The trial provides the opportunity to study epidiolex in a fourth childhood onset epileptic encephalopathy with a very high unmet need. 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 a more fulsome view of the potential effectiveness of Epidiolex in treating a broad range of seizure disorders. We also have a number of other near-term pipeline milestones, including the initiation of a third multiple sclerosis-related spasticity trial for nabiximols. Spasticity occurs in up to 84% of MS patients. and approximately one-third of those who experience spasticity live with uncontrolled symptoms. No new oral antispasticity medications have been approved in the last 20 years, and current disease-modifying treatments show no evidence in relieving the symptoms. So we have an opportunity to deliver a much-needed therapeutic option to the multiple sclerosis community. We are also planning to initiate Phase II clinical trials for JCP385 and JZP150 in essential tremor and PTSD respectively. We expect to initiate all three of these clinical trials this year. Moving to oncology on slide 12, I'll start with Rylase or JZP458. Given the significant need, we're very pleased FDA approved Rylase before the Phase 2-3 trial was complete. We believe this speaks to the need for Rylase to be available to patients as quickly as possible. Now that Rylase is approved in the U.S., we are turning our attention to analyzing additional data from the trial and submitting that information to FDA and other regulatory bodies. Currently, Rylase is approved for intramuscular administration, dosed every 48 hours at 25 milligrams per meter squared. We expect to submit a supplemental BLA to support a label update to include dosing intramuscularly at 25 milligrams per meter squared on Monday and Wednesday and 50 milligrams per meter squared on Friday. Giving a two-fold higher dose on Friday results in a higher level of 72-hour asparaginase coverage between the Friday and Monday doses. Our belief is that FDA will continue to move swiftly in its review process for Rite-Ace. The ongoing trial is also assessing intravenous administration of Rylase, which is common in Europe and other geographies. We are continuing to advance our regulatory strategy for Rylase outside of the U.S. and anticipate the data from our current development program will support regulatory filings in Europe in 2022. In addition, we are working with an in-country partner to advance the program for filing approval and launch in Japan. Moving to Zevzelka, I'll take a few minutes to provide an update on our development plans in small cell lung cancer and other potential indications. These plans include four trials that are underway or will be initiated in the next 12 months. After discussion with FDA, our partner PharmaMar plans to initiate a confirmatory trial in second line small cell lung cancer later this year. This trial is expected to be a three-armed trial comparing Zabzalka either as monotherapy or in combination with Irinotecan to investigators' choice Irinotecan or Topotecan. In positive, this trial would confirm the benefit of Zabzalka in the treatment of small cell lung cancer when patients progress following first-line treatment for the platinum-based regimen. The second trial, which we announced in June of this year, is a phase three trial to evaluate first-line use in combination with atezolizumab or Ticentric as maintenance therapy compared to Ticentric alone in patients with extensive stage small cell lung cancer after induction chemotherapy. The trial, which is expected to initiate later this year, is in collaboration with Roche. I am pleased to announce Jazz is also planning to initiate another Phase II basket trial in early 2022. to explore efficacy and safety of lurbanectin monotherapy in patients with select advanced or metastatic solid tumors. Cohorts will include advanced urothelial cancer, large cell neuroendocrine tumor of the lung, and homologous recombination deficiency, or HRD, positive cancers. In addition, we have initiated a phase four observational study to collect safety and outcome data in the real-world setting in adult patients with extensive-stage small-cell lung cancer. The primary objective of this study is to assess the effectiveness of sub-salk and monotherapy in terms of overall response rate in patients with small-cell lung cancer who progress on or after prior platinum-containing chemotherapy to generate additional real-world evidence data. This robust development program will enable us to evaluate Zypsalca in a range of settings and tumor types with the goal of identifying additional patient populations who can potentially benefit from receiving Zypsalca as part of their treatment regimen. Turning to Vixios, in our continued effort to deliver our therapies to as many patients as possible, I am pleased to report that Vixios is now approved in Canada and available to patients. continuing clinical programs to evaluate additional patient populations and indications. I'll conclude on slide 13. At the beginning of the presentation, Bruce stated that we were making notable progress in our transformation to an innovative, high-growth global biopharma company. A significant component of that transformation is continuing to enhance our R&D capabilities and productivity. Looking across our portfolio, this slide really highlights the breadth of our efforts. Seven mid- to late-stage trials are underway or will begin within the next 12 months, including two registrational trials designed to evaluate new indications for approved therapies. We are making strategic and science-driven investments across the neuroscience and oncology portfolio to deliver therapies to patients. The GW cannabinoid platform adds exciting new direction for our development efforts, and we remain focused on having the right talent and resources in place to advance innovative, internally developed therapies, along with the expertise to identify promising external opportunities. We are proud that over the past several years, we have built a sustainable, productive R&D engine at JAS that delivers innovative therapies for patients, and also value for the company and its shareholders. I'll now turn the call over to Renee.

Thanks, Rob. On today's call, I'll highlight several key items from the quarter. Full financial results are available in our press release and 10Q. Outlined on slide 15, our second quarter financial performance demonstrated continued top-line revenue growth including a meaningful and growing contribution from our recently launched and acquired products. Total revenues in the second quarter were $751.8 million, an increase of 34% compared to the same period in 2020. This double-digit, year-over-year revenue growth was driven by our Oxivate franchise, the continuing success of Zepzelka, and the addition of Epidiolex. with the latter two clearly demonstrating our ability to put capital to work to build sustainable growth. Consistent with this approach, we continue to expect the GW transaction to be accretive in 2022 and substantially accretive thereafter, and to provide accelerated double-digit top-line revenue growth. We're on track for another year of strong financial performance and sequential revenue growth and we expect to exceed the significant milestone of $3 billion in annual revenue this year. We've made substantial progress towards our goal of revenue diversification, with 41% of net product sales in the second quarter coming from products that have been launched or acquired since 2019. And we're well on track to generate our target of at least 65% of net product sales from these products in 2022. Adjusted net income for the second quarter was $241 million, an increase of 16% over the same period in 2020, coupled with adjusted EPS growth of 5% year over year to $3.90 a share. Maintaining strong cash generation remains a key focus as well as rapid deleveraging to meet our target of less than three and a half times net leverage by the end of 2022. We will also continue to make disciplined investments to grow the business, including investments in the ongoing commercial launches of ZyWave, Zepselka, and Rylase, the growth potential of Epidiolex, the anticipated launch of ZyWave in IH, our R&D pipeline, and the GW cannabinoid platform. We provided financial guidance in mid-June following the close of the GW acquisition. On a non-GAAP basis, we are reaffirming that guidance today. Total revenue guidance is in the range of $3.02 billion to $3.18 billion, and non-GAAP adjusted EPS is in the range of $13.40 to $14.70 per share. This guidance includes the addition of GW from the date of closed to year end, approximately eight months. We have updated our GAAP guidance primarily to reflect the impact of the UK Tax Act, which was enacted in June following our guidance update. Turning to slide 16. We're pleased to be on track to deliver on the key objectives and milestones outlined for our business. Our R&D organization continues to evolve and expand its capabilities with the recent FDA approval of Rylase enabling our fourth new product launch since the beginning of 2020. With ZyWave and IH approaching its PDUFA date next week, We are solidly on track to meet our goal of five product launches in two years. And we are initiating multiple mid- and late-stage clinical trials in the next 12 months from both the Legacy Jazz and GW pipelines. Our commercial teams have demonstrated strong performance on the launches of ZyWave and Narcolepsy and Zepselka, And we expect that momentum to be carried forward in the launch of Riley's and anticipated launch of ZyWave and IH, as well as the continued growth of Epidiolex. We're pleased with the performance of Epidiolex and continue to be impressed with the cultural fit and progress on integration, further increasing our confidence in the success of the GW transaction. Our disciplined capital allocation has enabled us to expand our pipeline and diversify our revenues, and we are well positioned to continue to invest both internally and in our corporate development efforts to drive sustainable long-term growth and shareholder value. Our transformation to an innovative, high-growth, global biopharmaceutical company is well underway. This concludes our prepared remarks. I'd now like to turn the call over to the operator to open the line for Q&A.

As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. As a reminder, callers will be limited to one question only. Please stand by while we compile the Q&A roster. Your first question comes from the line of Ken Keshatori of Calvin and Company, your line is open.

Hi, thanks team for the commentary around generic Xyrem triggering events. Just a couple questions around it. Is this for all of the settlements or is it for selected generics? And then trying to understand if there are any volume restrictions or is the triggering event limit or unleash all kind of volume restrictions that you may have. And then Obviously, just would like to hear any commentary on how you think this would evolve, the marketplace would evolve, the language around ZyWave and the orphan designation clearly incredibly favorable. So just trying to get a sense of how you think managed care would handle the generic optionality with that type of language that ZyWave has. Thank you.

Yeah, thanks, Ken, for your question. So, again, as Dan mentioned in his remarks, we view it as upside if the ZyWave launch is going so well that, in fact, ZyRAM revenues have dropped to the point that this kicks in. But to your specific questions, that would trigger an earlier launch of the first AG, which is HCMAS. The other AGs, which are all volume-limited, as you'll recall, to each a low single-digit percentage or a single-digit percentage of prior year volume, even collectively the three volume-limited AGs wouldn't add up to all that much volume. Those would track six months after HCMA, so they are accelerated but not to the same date as HCMA, to a date six months later. And there would be no impact of that acceleration of the AG launches to the generic launches, which would be allowable as of the beginning of 2026. So no impact on the volume restrictions, which is one of your questions. In terms of how the market will evolve, You know, we're very pleased that the availability of a lower sodium product, which we believe is a healthier, lifelong treatment option for patients, is being well received by physicians and patients. And as we've said, as we look out into 2023 and we pick that year to be a year where there could be multiple other OxyVe products on the market, we still continue to believe Zywave would be the dominant brand and have – you know, have the most patients. We've got strong commercial coverage for both Xyrem and ZyWave. We don't see that changing in the future. And again, if you can imagine patients being well controlled on this lower sodium product, and remember that lowering is a 92% reduction, to move those patients back to a product that would then have more than 10 times the sodium level, you know, up to a full gram and a half or more of extra sodium per night when it's known that sodium matters in terms of impact on cardiovascular comorbidity. And we know that the narcolepsy population is itself at higher risk on cardiovascular risk. You know, we just think that it will be clear to people the better choice for ongoing therapy.

Great. Thank you.

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

Hey, guys. Good afternoon. Thanks for taking my question. I have one short one, so I'm going to try and sneak in a second one as well. The first one is, what was the year-over-year change in the Oxibate revenue bottle volume this quarter? And the second one is, Can you frame for investors the reason for either confidence or caution heading into the DIMBICS Model Space 3 data in MS spasticity? And can you provide the timing for the readout of each of those trials?

So thanks, Jess, for your one short and then one full question. We'll let you get away with that. Maybe I could ask Dan to take the first part of your question, which was really around oxibate volumes. And then perhaps I could have Rob comment around your questions about the Nebiximol's clinical program. Dan?

Yeah. Thanks, Bruce. So, Jess, we were very pleased to see that the overall OxyBait market showed a 5% year-over-year increase. You know, we referenced that our sales were a 3% increase. And so you can imagine, as we had said with ZyWave, and as we were ramping up commercial coverage, we wanted to make sure there was no inability for patients to access therapy, so we had a range of bridging programs. The good news is, as we emerge from the second quarter, we have over 80% coverage now, and it's continuing to increase, and so we expect that revenue bottles will be tracking to patient growth, and you'll see that in the coming quarters. But we're not giving specific bottle volume numbers at this point.

Just for this quarter or going forward?

Going forward. Okay.

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

Hey, just before we go on, I think there was a question on the Biximals, too. And, Rob, if you want to address that, that would be great.

Yeah, actually a question, Jeff. So, we have a comprehensive program for nabiximol to provide that bridging between already strong data that allowed approval in many jurisdictions outside the U.S. That's in MS five studies, in spinal cord injury two studies, and some of them are already underway. And we expect that as they read out, they potentially will give the opportunity to provide enough reading data for submission in the U.S. I don't know that we've given specific timings around the readout of each of those studies.

And, Jess, just to follow up, we went back and checked the language in our queue, which you'll be able to see soon, and we did give revenue bottles a figure of down less than 1%. year-over-year for the quarter across OxyBait. Operator, I think we were going to go to Jason.

Yeah. Hey, guys. So I just wanted to follow up on Ken's question, actually. So, Bruce, is it your interpretation that the ZioWave orphan exclusivity would pertain to potentially blocking approval of any high sodium composition of oxibate, or it would seem to us that it's exclusive to kind of lower sodium composition since that was the basis of the clinical superiority finding, but I just wanted to run that by you.

So, Jason, my understanding is the orphan drug exclusivity granted to ZyWave means that no other oxibate product should be approved in narcolepsy unless FDA determines that it is superior to ZyWave, which the FDA can do on a variety of measures potentially.

So by that interpretation, generic ANDAs of high sodium should not be approvable?

I think we're talking about new approvals.

Which there hasn't been other than... Right. We've only had HICMA get approved and they've discontinued, I think, their approval. So there aren't approvals technically of generic ANDAs. So I guess all the others would technically be gated by the ODE period?

I think historically it's been FDA's view that orphan exclusivity does not block approval of generics to... a product on the market.

Okay.

All right. Thank you.

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

Hi. This is Melina Santoro on for Jeff. Thanks for taking our question. Can you tell what the breakout is of Epidiolex by indication and kind of what you see as the key growth driver going forward, and also what kind of impact you're expecting from off-label indications. Thank you.

So, Dan, maybe I'll let you talk to how the evolving launch of Epidiolex continues to progress and where we see use coming from now and in the future.

Yeah, thanks, Bruce. So on the Epidiolex US launch, we're really pleased with the performance to date and what has been accomplished even in the midst of the COVID pandemic that dampened down some of the new patient starts. We see continued penetration into the current indications, and in particular TSC, which was just recently launched in the fall of last year, both the number of patients available but also higher doses Clearly, we see opportunity to go beyond the three indications and seizure types into EMAS, so we're excited to move into that area. As we referenced but didn't put a lot of substance behind it, the European and international rollout continues to progress nicely, too, with recent reimbursement now in four of the five major European countries. So we also see continued contributions and growth from the international markets going forward.

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

Thanks. I just wanted to continue on the theme of Epidiolex. Can you just talk about what your penetration is in the three approved indications, even if you can't go into specifics just qualitatively, what you're seeing? And then secondly, how should we think about patient attrition or patient attrition rates across the approved indications or even just overall? And do you expect that with the easing of the pandemic, Delta COVID notwithstanding, that attrition rates might attenuate to some extent with some greater normalization of in-office visits, if you will. Maybe help us understand your thought process there. Thanks.

Thanks, David. Dan, do you want to take that?

Sure. Yeah, so persistency is definitely a hallmark of the brand and something we saw both in the diligence and continue to see in the market. It makes up the dialects. Particularly important in this refractory epilepsy setting, which is a polypharmacy, is it's a unique mechanism of action relative to the other anti-seizure medicines. We really see it becoming a cornerstone of therapy for those patients. Often, if benefit is being derived from the drug, it's continued and there may be some tinkering around the edges with other therapies. With or without COVID, we think persistency is going to be a hallmark for the brand. In terms of penetration rates, I know GW did give a number last year by indication. Those are the only numbers kind of out there, and that was a single point in time. I think we have an opportunity as we're going post-COVID and seeing patients return to the clinic that an increasing number of patients will be available to access. There's Definitely a reluctance to put these pediatric kids at risk to tinker with their medicines where there could be an ER visit or something else if it doesn't go quite right. So kind of post-COVID, we see a lot more opportunity for fine-tuning those therapies without that concern.

And since I took the opportunity to clarify one of Dan's answers earlier, I'm now going to take the opportunity to clarify one of my earlier answers. and say that when I said that ZyWave ODE would be unlikely to block ANDAs to an existing approved product I meant to Xyron, it would block any ANDAs to ZyWave for the period of ODE exclusivity, which is seven years from ZyWave launch date. Operator?

You're next. Mm-hmm. Your next question comes from the line of Gary Nachman of BMO Capital Markets. Your line is open.

Good afternoon. Given that ZyWave's share of total OxyBase patients has accelerated nicely since launch, now you're at about a third of total, it sounds like we're reaching a point where that will level out more. Perhaps there was some lower-hanging fruit with the early adopters, like Dan said earlier. So just briefly, walk through the next steps of the ramp in more detail, how you plan to broaden the prescriber base and, you know, patients that are xyron naive versus switches from xyron. And then with IH, if you get that approval, do you think that's going to further provide a tailwind for the narcolepsy indication as well? Thank you.

Yeah, Gary, thanks for those questions. And, you know, let me just be clear. We think ZyWave is the better product for all patients, and our goal would be to make that therapy as available to as many existing OxyBait and new OxyBait patients as possible. We're certainly ramping up our efforts, as Dan talked about, to go after those physicians who have not yet been as frequent prescribers or prescribers at all of ZyWave to date. So we've got some work to do, but we're continuing that effort to try to bring this product to them. Maybe I'll let Dan comment on your point about whether IH provides any additional impetus moving forward. Dan?

Yeah, thanks, Bruce. Yeah, we're very, very excited for the IH indication coming up. And physicians have seen the clinical results at some of the recent conferences and We've been doing disease education among physicians and patients. And as the only medication available with some outstanding clinical results, we do think that will make a difference across those offices, including those that may not have fully adopted ZyWave and narcolepsy yet, because this will be the one and only approved therapy. The good news is the market's concentrated. It's the same physician audience that we're calling upon. And so I do think it One, it's an opportunity in and of itself, but two, it does create additional opportunity for interactions with the HCPs, including those that may not have fully embraced ZyWave for narcolepsy.

Great. Thank you.

Your next question comes from the line of Annabel Samimi of TIFO. Your line is open. Hi.

I had a quick question regarding nabiximols. You have the Phase III MS spasticity study ongoing. Is the goal to get a broad label with this MS study? Are you also seeking the SCI? Do you have to do additional studies there? And when should we be expecting submission of this? And just one other question on nabiximols. You have a study, I guess there were some plans for PTSD as well, but you have the JCP 150 planned phase two for initiation at the end of this year. Do you plan on reprioritizing the PTSD for nabiximols and prioritizing 150? Thanks.

Thanks, Annabelle. Rob, let me come to you for the Nabiximols and the PTSD.

Thanks, Bruce. So, you know, as we mentioned earlier, we have a comprehensive program which reflects input from FDA around how best to bridge from all the, I would say, the voluminous data that already existed and supported approvals around the globe. We chose to study two indications in particular and whether Ultimately, a label would be broader than that, I think would be, you know, determined, you know, upon review. In terms of the earliest that we could possibly submit, we do think there's meaningful data that will come out of each of those studies that are planned and with several ongoing. And that would mean that the earliest possible to support an NDA submission could be within the next one or two years. And then we haven't provided any details, you know, on prioritization of PTSD. I mean, we are excited to be working in this field, where there's really a substantial unmet medical need, and now we have several mechanisms within our portfolio that potentially could address it. So we've discussed the JCP150 program, but, you know, certainly have significant expertise in that space, and we'll be looking to leverage that further. The 150 program, as I mentioned in my earlier remarks, we're excited to be starting that trial this year. Yes, thank you.

Your next question comes from the line of Esther Rajavelu of UBS. Your line is open.

Hey, thank you for taking my question. Can you talk about the inventory dynamics for this quarter and also the Any color you can share on what you're seeing with regards to duration of therapy as you're moving more into the second line, that would be helpful.

Yeah, so Dan, do you want to take the inventory and demand question, and then for Dan or Rob, any comments on duration of Zepselka therapy?

Sure. Yeah, with a rapidly... The rapidly adopted new therapy, it's not unusual for distributors to carry a little bit of excess inventory at the beginning. And then as you start to see a little more of the real usage trends and more consistent pattern of ordering to get them down to a lower level since we can ship product to the wholesaler and to the clinic pretty quickly. So that's what we're saying is the underlying demand growth is what's relevant, the 9% growth. and that's going to be more reflective, we think, of the X factory growth. We'll be closer to that demand growth. What we're focused on, of course, is establishing a standard of care. We do look at monthly chart reviews, and we see continued penetration into all sectors of those parts of second-line therapy. As you get to the patients who have better prognosis, particularly platinum-sensitive patients, there's an opportunity to have much longer clinical benefit and more therapy. You know, exactly the duration of therapy, we need a little more time to see that market mature, but what we're happy to see is that the percentage increase in the standard of care in those settings is continuing to increase and exciting now for the additional data that will come from the trials that are pending.

Rob, would you like to add anything? Yeah, thanks, Bruce. I would just reinforce a few things, you know, not speaking to specific data, but just what we're hearing in the field from our medical personnel is that what they're seeing is what we saw in the clinical trials. So good responses in patients, and as Dan mentioned, you know, patients who had had an initial good response and relapse tend to do very well on Zypselka. Also, the tolerability has been very good, you know, in the clinical trial that supported We had less than 2% dropout due to toxicity, and so sepsilca has a favorable tolerability profile and can be continued without discontinuation for the great majority of the patients, you know, until disease progression. I would also just take the opportunity to just comment on our excitement around the first-line trial that we plan to initiate this Later this year, this is first line extensive stage small cell lung cancer, whereas Abcelka will be add-on to the standard of care in that line, which includes atezolizumab. This gives us a chance to intervene on patients who have minimal residual disease. Most commonly, they do have active residual disease, but they've experienced a response or some benefit from their initial chemo, but have to stop that chemo. It's an opportunity to intervene earlier before those patients progress and then often are in, you know, difficult situations to initiate a subsequent therapy. And we hope in that setting the duration of therapy would be even longer in a population of patients. It's even higher really to extend that period of progression-free survival where patients feel well and are experiencing a high quality of life.

Awesome. Thank you. Your next question comes from the line of Mark Goodman of SVV Learing. Your line is open.

Mark, are you there?

Hi, can you hear me? Yes, we can. Can you hear me now? Sorry about that. I was wondering if you could comment on cost synergies, where we are with respect to how much we've achieved so far, what we're thinking about for next year. and if we found some other places for some synergies. Thanks. Renee?

Yeah, thanks, Bruce. And Mark, I'm happy to address that. So when we announced the transaction, we announced that we expected to achieve about $45 million synergies in the first full year of following the transaction. So that would be next year. We've also said, of course, that this transaction is really not about cost synergies, but where we are today and as we're looking at 2022, I feel very confident that we'll be able to achieve these synergies. And as we've said in the past, where we would expect these to come from is some of the typical overlaps between functions that two public companies would have that you really wouldn't need to duplicate in bringing them together. And as we've been working through our integration, being able to integrate the teams across the board, we've really had great success at being able to recruit talent, ensure that the teams are integrating well, that we're able to get our R&D colleagues working together rapidly because we do see good synergies there with respect to the ability to have the teams working together, collaborating together, and being able to accelerate some of our work on the pipeline side. So big picture, we're in great shape with respect to being able to identify our cost synergies, and as we've stated previously, that's unlikely to come from very much in the tune of an employee overlap. It's really more in some of the functional areas that you wouldn't need to have for two public companies, such as boards and directors and that sort of thing.

So you're basically saying that their G&A was about $45 million, and that's what you're taking out, and that's about it?

No, Mark. I'd say that's a little simplistic. As Renee said, there are lots of duplicate costs we don't need and are eliminated. She gave the example of the board of directors. We're not going to have two CEOs going forward, for example. There are places we can be more efficient as a combined company, and essentially we were a growing company continuing to add employees. GW was a growing company. company continuing to add employees sometimes by putting the companies together we're going to need to add still need to add employees but not as many as we each would have needed to add individually so it's savings like that thanks your next question comes from the line of greg silvana of goldman sachs your line is open

Great, good afternoon. Thanks for taking my question. It's on Zipzelka, and I just wanted to revisit the growth that you're seeing thus far. So at 8% to 9% quarter-over-quarter growth over the past several quarters, is it fair to assume that as a steady state base case assumption, that's what we should be thinking about, or perhaps even slightly moderating as we look over the next several quarters? And as a follow-up to that, when would you suggest that we consider the potential for any meaningful potential acceleration in that growth dynamic? And if I could sneak in another question just around expectations around the launch trajectory of RILAs, and how would you suggest we consider modeling at least the initial uptake curve? Thanks so much.

Yeah, so Dan, maybe I'll let you take the Zepzelka growth question first.

Sure. Yeah, so I think we still see, you know, growth and opportunity for penetration in the second line. Of course, as we move into second line, you know, patients who then had prior exposure to Zepzelka, if they go on to third or fourth line, you know, will not be candidates. And we did have, at the beginning of the launch, some bolus of patients who were in later lines of therapy that The good news about increasing the rate of adoption, second line, is obviously those patients can benefit more from the therapy, particularly as we move into patients with more platinum sensitivity. And then even beyond that, as we start to get clinical data from the first line study and the real world studies, it will help give confidence to use the drug more broadly. So that's what I would say. It's a little too early to, we're not giving forward guidance, but we do see continued growth in the brand going forward.

Yeah, on Riley's expectations, it's important that we now reestablish confidence in the marketplace that any patient that needs access to an erwinia asparaginase after they show a hypersensitivity reaction to E. coli-derived asparaginase can get the product. You know, as Rob said, we're working to update the label over time with different dosing flexibility. But really, we think we've given people the opportunity not only to treat their patients, but to really treat them with a product that was designed to provide the best coverage of active enzyme love threshold levels during the dosing interval. That's been our goal is best therapy for patients. You know, we'll work to establish that credibility quickly. You know, we mentioned at the time of launch we had a year's supply available, so we want people to know they don't need to worry about it. The ordering procedure is easier for Rylase than it had been with the predecessor product given some of the issues we had to deal with there. You know, the NCCN adding it so quickly to guidelines was very helpful to us. COG's partnership during development and their awareness through the clinical trials of where we were, you know, with COG-associated physicians doing most of the prescribing for this product all will help. But we're just getting started. We'll have more to say over the months to come. You know, recall that at the time of our launch there was limited information Erwin A's supply in the marketplace that is out there now as well for at least a little while. So we'll see, we believe, a transition here as people become aware of the new product and what we think are some of the benefits of the way we develop the product and its high quality and reliable supply. Dan, anything else you want to add on expectations in the near term?

No, I think you covered it well. I mean, obviously, we're going to be supplementing the current indication with additional data as we expand to Monday, Wednesday, Friday IV, and then, of course, get the product to the market outside the U.S. and Europe, Japan, and other regions. In some of those regions, like Japan, we never had product availability or the quality that could support the introduction into those markets.

Okay. Thanks, Bruce. Thanks, Anne.

Your next question comes from the line of Greg Fraser. Your line is open.

Good afternoon, folks. Thanks for taking my question. For the physicians who have not broadly adopted Zywave, has it been more about hesitancy to switch patients who are stable on Zyrem or some other reasons that you've heard?

Dan, do you want to take that? Sure.

Yeah, I mean, it's a little different for everybody, but, you know, new product launches, there's obviously... slow adopters and faster adopters. The good news is that the faster adopters were high-volume prescribers, more associated with the KOLs and aware of the benefits. With the ODE, it clearly gives some wind at the sails as we go into offices, including kind of the lower-volume offices. And then some of these physicians are a little more reluctant to take a stable patient or at least wait until the patient's up for a prescription. I think as physicians are gaining increasing experience and we have these high-volume practices, some of which have largely adopted ZyWave, they can see the same great efficacy and it's easy to transition the patient's dose for dose over. And so the peer-to-peer discussion will also be beneficial for penetrating into the offices where ZyWave has not yet been adopted or hasn't been fully adopted.

Rob, anything you want to add on this one?

Yeah, I would just say from the anecdotes that we're hearing from the medical staff in the field is that there's no issues. When they talk to physicians about the importance of lowering sodium in narcolepsy patients for this lifelong therapy, there's a lot of receptivity. And especially, I would say, since the granting of ODE and the FDA's It's just really resonating well, and I think it's probably a matter of time.

Great. Thank you.

Your next question comes from the line of David Steinberg of Jefferies. Your line is open.

Thanks. I have two questions, one very near-term related and one longer term. So first on the near-term question, next week is your PDUFA date for ZyWave and IAH, and I'm just curious – Are you in labeling discussions or have you concluded labeling discussions? I assume you are in them or have concluded them. Can you confirm that? And then secondly, just a longer-term tax rate question. At the beginning of the year, you guided to 16% to 18% pre-GW, and upon closing, a pretty significant cut in the range of 300 basis points to 13% to 15%, at least for this year. Obviously, that reflects the mixed shift. to Epidiolex with the UK-based tax jurisdiction, but obviously with Zywave growing rapidly and, again, a more favorable tax jurisdiction as well as a number of NOLs from GW, should we assume that the 13% to 15% tax rate is the new normal longer term, or were there some one-offs just for this year and that that tax rate will be above that 13% to 15% starting next year? Thanks.

David, I'll take the first part about the PDUFA date upcoming and then turn it over to Rene on tax matters. You know, as Rob said, we think we're right on track. We're not going to get into and generally don't get into back and forth with FDA specifically, but things are progressing the way we expected, and we're looking forward to bringing ZyWave to patients with IH as soon as we can. Rene? Okay.

Yeah, and on the tax side, so we have stated previously that when we look at our future product mix, as we continue to diversify, this group of products that we're diversifying into is expected to have a favorable impact to our ETR. And that's based on a number of factors, IP, where product is manufactured, other impacts related to our business And there was, as we shifted from the beginning of the year to coming out with our updated guidance in June, this shift downward to reflect both the addition of Epidiolex and then as we continue to look at that shift into our newer products with those products coming together, those are the ones that carry a more favorable ETR. And, of course, we also continue to look longer term. While we're not going to give a specific range here today, I would just say going forward, as we continue to diversify and we're building that portfolio of future products, we'll continue to look at how we structure those in the most economically favorable way.

Great. Thanks.

Your next question comes from the line of Balahi Prasad of Barclays. Your line is open.

Hi. Good afternoon. Thanks for the question. Just a couple from me. Firstly, on Synosy, you rejected the sales team around February, March, and also commented that there's highly promotions on Stave, so I was thinking that we would probably see stronger numbers, but could you maybe take us through the progress achieved in the background on this, and also maybe revisit the overall market growth on longer-term outlook that you have for 2025? Thanks.

Sure, I'll take Sanosi. Yeah, so we, you know, we reformed our field teams and made sure that we've got a dedicated, you know, field team to call upon the Sanosi doctors and We do think it's promotionally sensitive and with increasing, you know, restrictions getting lifted and more, you know, face-to-face interaction, we're still below COVID levels in terms of the percentage of, you know, in-person versus virtual. So we're seeing that continue to increase and making sure that there's real awareness of Sanosi. You know, for those physicians who've adopted it and for patients who've gone on, the clinical profile really fits with what we saw in the clinical study. I think we are seeing sometimes for physicians who haven't had experience yet that there's just a general reluctance or concern about market access with new branded therapies. Given that we've got very good market access, it's something we're trying to address with more in-field education. Overall, 25% prescription growth. We continue to think that there's room for upside. We're not updating longer-term potential, but we do think It's got sort of meaningful clinical benefits relative to the current wake promoting agents and stimulants that are being used.

OK, operator, I think that was the last question. So I'm going to conclude just conclude by saying we remain focused on our key objectives for 2021 and we're excited about the progress of our transformation. I would say the first six months of this year have been a good demonstration of the power of our products, our platform, and our people, and we're looking forward to continuing the momentum. I'd like to close today's call by recognizing our Jazz colleagues, including those who recently joined us from GW, for their creativity, commitment, and the strong sense of urgency that continues to fuel our success. I also want to thank our patients, our partners, and shareholders for their continued confidence and support. We look forward to speaking with many of you at upcoming fall investor conferences. Thanks, everyone, for joining us today, and stay well.

I will turn the call over to Dan Fisher for the closing remarks as well.

Nope, those were the closing remarks, operator. Sorry for any confusion. We're all set.

This concludes today's conference call. Thank you for participating. You may now disconnect.