Jazz Pharmaceuticals PLC (JAZZ) 2020 Q3 法說會逐字稿

Welcome to the Jazz Pharmaceuticals Plc Third Quarter 2020 Earnings Conference Call. (Operator Instructions)

I will now turn the call over to Kathy Littrell, Head of Investor Relations at Jazz Pharmaceuticals.

Thank you, [Sino], and thanks to those of you joining our investor call. Today, we reported our third quarter 2020 financial results and updated our financial guidance for 2020. The press release and the slide presentation accompanying this call are available in the Investors section of our website.

On the call today are Bruce Cozadd, CEO; Renée Galá, CFO; Dan Swisher, President; and Rob Iannone, Executive Vice President, R&D. Joining for the Q&A session are Kim Sablich, Executive Vice President, General Manager of North America; Phil Jochelson, Neuroscience Therapeutic Head; Anne Borgman, Hematology and Oncology Therapeutic Head; Sam Pearce, Senior Vice President, Europe and International; Shawn Mindus, Senior Vice President, Strategy and Finance; and Larry Carter, Global Development Lead Neuroscience.

I'd like to remind you that today's call includes forward-looking statements, such as those related to our future financial and operating results, and which involve risks and uncertainties that could cause actual events, performance and results to differ materially. We encourage you to review statements contained in today's press release and our latest SEC disclosure docs, which identify certain factors that may cause the company's actual results to differ materially from those projected. We undertake no duty or obligation to forward -- to update our forward-looking statements.

On this call, we discuss non-GAAP financial measures. Reconciliation of GAAP to non-GAAP financial measures discussed on this call are included in today's press release and slide presentation available on our website.

I'll now turn the call over to Bruce.

Good afternoon, everyone, and thank you for joining us. In the third quarter, we delivered strong financial and operational results that build on the significant progress we made during the first half of the year. We executed on our key objectives, positioning us to deliver significant value and long-term growth. Since mid-year, despite ongoing impacts from COVID-19, our team has worked diligently to advance our strategy and align with the goals and milestones we set for Jazz at the beginning of the year, including 5 key product launches in 2020 and 2021. Our focus on transforming our business through execution across regulatory, commercial and R&D operations has continued, and today, we achieved another exciting milestone in our neuroscience franchise with our U.S. launch of Xywav for EDS and cataplexy and narcolepsy. We strongly believe, based on more than 15 years of engagement with sleep specialists and patients, that reducing the lifelong burden of high sodium intake is an important advance for oxybate patients. We are working hard to optimize our patient and physician education initiatives to ensure that existing and new oxybate patients fully understand this benefit.

Additionally, last month, we announced positive and compelling topline data for JZP-258 in idiopathic hypersomnia, or IH, bringing us another step closer to improving the lives of IH patients for whom there is no approved therapy. We look forward to submitting our sNDA in the first quarter of 2021 and are targeting launch in the fourth quarter next year. Our launch of Xywav and narcolepsy today, coupled with our progress toward launching an IH next year, continue to give us confidence in the ability of our oxybate franchise.

Another important milestone this quarter was the launch of Zepzelca in the U.S. This successful launch demonstrated both our agility and our strong commercialization capabilities, progressing from a deal announcement to launch in a matter of months. Zepzelca represents a major advance for patients with relapsed small cell lung cancer and is the first approved therapy in the second-line setting in over 20 years, giving physicians an important new tool in the management of this disease. Our team is executing exceptionally well, and I'm pleased that physicians have enthusiastically embraced Zepzelca's benefits and profile.

Through flexibility, innovation and commitment, we remain on track to execute on our important objectives across product launches and pipeline advancements through 2020 and 2021 with 3 launches already underway and 2 planned for next year. Our overarching priority is to develop and bring new life-changing medicines to patients in areas of high unmet need. To that end, this year ranks as one of the most productive in Jazz's history.

I'm excited about the future. With continued innovation, our strong commercial franchises, a robust and productive pipeline and our commitment to investing in and leveraging our global platform, we are well positioned to change the lives of more patients and deliver tremendous shareholder value.

I'll now turn the call over to Renée for a financial update, Dan will then give an overview of our commercial performance, and Rob will provide an update on progress across our R&D programs.

Thanks, Bruce. I'm pleased to share our financial results this quarter, which reflect strong top and bottom line growth, including a meaningful contribution from our recent launch of Zepzelca. With our strong financial and operational performance this year, we are poised for growth in revenue diversification as we continue to make substantial progress towards our goal of delivering nearly half of our 2022 revenues from products launched since 2019.

Total revenues for the third quarter were $601 million, representing an increase of 12% over the same period last year, led by double-digit growth in our oncology portfolio. Excluding Erwinaze, where sales have been significantly impacted by supply constraints, total revenues increased 15% in the third quarter compared to last year. Oncology net sales increased 37%, driven by a robust launch of Zepzelca that generated net sales of $37 million in its first quarter on the market and a $13 million increase in Defitelio net sales as physicians resume stem cell transplants that had been delayed due to COVID-19. Neuroscience net sales grew 7% in the quarter, led by continued strong performance at Xyrem.

Turning to operating expenses. Our adjusted SG&A expense increased by $28 million compared to the third quarter of 2019, driven by targeted investments to support our multiple commercial launches. During the quarter, we also recorded a $10 million acquired IP R&D expense related to our expanded collaboration with RedX Pharma. Our disciplined approach to capital allocation combined with our top line revenue growth is enabling us to make significant investments in our business while still delivering growth in our non-GAAP adjusted EPS, up 5% over the same period last year, resulting in non-GAAP adjusted EPS of $4.31 a share.

Turning to guidance. As we approach the end of the year, we're taking the opportunity to update our full year 2020 financial guidance. On the top line, we are raising our total revenue guidance to a range of $2.32 billion to $2.38 billion, which represents an increase from our prior guidance of $75 million at the midpoint. For oncology, we're increasing our net sales guidance to a range of $525 million to $565 million, reflecting the robust launch performance of Zepzelca and improved trends for Defitelio and Vyxeos. This updated guidance represents a $60 million increase at the midpoint from prior guidance. In neuroscience, we are raising the lower end of our net sales guidance to a range of $1.76 billion to $1.8 billion to reflect continued strong performance of this business. As a reminder, we expect minimal sales of Xywav in the fourth quarter. Also, throughout our Xywav launch, we expect both revenue bottle growth and gross to nets to be impacted by our investment in patient access programs, which are designed to enable seamless access to the product while we obtain broad commercial payer coverage. The launch of Xywav and narcolepsy today, coupled with the potential launch of JZP-258 in IH next year, reinforce our confidence that oxybate will continue to be a key revenue contributor for many years.

Now turning to our expense guidance. Given our strong operational performance and ability to navigate the impacts of COVID-19, we have increased our adjusted SG&A guidance to a range of $735 million to $765 million to reflect further investment behind our commercial launches. Our adjusted R&D guidance remains unchanged. We are raising the lower end of our guidance for non-GAAP adjusted EPS to a range of $12.20 to $13 per share while continuing to invest in the diversification of our pipeline. As reflected in the $46 million increase in acquired IP R&D expense, which includes the $10 million upfront payment to RedX as well as a $35 million upfront payment to SpringWorks in the fourth quarter. As a reminder, we no longer subtract payments of this nature from our adjusted net income.

Turning to our balance sheet. Year-to-date, we have generated $713 million in cash from operations and ended the quarter with cash and investments of $1.9 billion. Driving sustainable and robust profitability and cash flow remains a priority, and our healthy balance sheet and liquidity gives us the capacity to pursue a broad set of corporate development opportunities. With recent transactions such as the collaboration with RedX and acquisition of the FAAH Inhibitor Program from SpringWorks, we have expanded our neuroscience and oncology pipeline with innovative assets. The RedX deal is a great example of how we externalize research with very capable partners to pursue specific pathways of interest. And the SpringWorks transaction brings global commercial rights to a promising Phase II ready asset that is strategically aligned with our portfolio and has large market potential.

Finally, our transaction with PharmaMar, which closed at the beginning of this year, enabled us to rapidly convert cash on our balance sheet into a revenue-generating asset that we expect to deliver meaningful growth and diversification for the company. With a substantial balance sheet combined with productive growing capabilities across development, regulatory and commercial, we look forward to leveraging our strength in corporate development to continue to drive long-term value for the company.

I'll now turn the call over to Dan.

Thank you, Renée Galá. 2020 has been a catalyst-rich year for us, and I'm pleased we've achieved multiple key objectives across our commercial and regulatory organizations, including FDA approvals of Zepzelca and Xywav and 3 product launches: the European rolling launch of Sunosi in May, the U.S. launch of Zepzelca in July, and today's launch of Xywav in the U.S. for the treatment of narcolepsy. With many of our engagements this past quarter with physicians, payers and regulators being virtual, our strong operational performance reflects the agility and commitment of our innovative teams as well as the therapeutic value of our products.

Xyrem delivered strong results, despite the challenges of COVID-19 pandemic. In the third quarter, Xyrem volume increased 4% compared to the same period last year, reflecting strong patient persistence and compliance. The average number of active Xyrem patients is 15,075, an increase of 2% from the same period last year. New patient diagnoses and enrollments continued to be negatively impacted by COVID-19 during the quarter, and we expect the impact to continue during the pandemic. However, we were encouraged by an upward trend in new patient enrollments during the quarter as more sleep centers reopened and as patients with more severe symptoms were prioritized. Although we observed in this quarter a slight COVID-19-related increase in demand for patient assistance and government programs, there was no meaningful mix -- or no meaningful shift in the payer mix.

Turning to Xywav, which is now commercially available for narcolepsy patients, following the rapid implementation of our REMS. Xywav is the first and only lower sodium oxybate approved for the treatment of cataplexy, or EDS, in narcolepsy and represents a significant advance for patients. Our launch efforts are focused on unlocking the potential in narcolepsy through awareness programs for physicians and patients to ensure their understanding of the lifelong burden of narcolepsy and high sodium intake. Additionally, our health care provider education is emphasizing the importance of patients' total health. I'm pleased that today, on our first day of launch, Xywav has coverage on the Express Scripts National Preferred Formulary for commercial lives.

While we continue to secure additional commercial payer coverage, we have robust patient assistance programs in place to help reduce barriers to initiating Xywav treatment, which is particularly important for those patients who may not yet have commercial coverage at launch. Our goal is to have the majority of oxybate patients on Xywav by 2023. As we think about the launch curve, our expectation is that patients will adopt Xywav over time. We know that patients don't see their doctor each month and many may still have Xyrem in their medicine cabinet, and they will finish their Xyrem supply before seeking a new script. We expect Xywav to become the oxybate treatment of choice of all patients, including current Xyrem patients, patients who previously were not prescribed Xyrem based on sodium concerns and newly diagnosed narcolepsy patients. Additionally, with the recently announced positive Phase III topline results in idiopathic hypersomnia, we look forward to bringing JZP-258 to the IH patient population next year.

Turning now to Sunosi. During the quarter, we were pleased with Sunosi's continued progress and growth in new patient starts, despite the continued challenges in engaging with pulmonologists who are on the frontline managing COVID-19 patients. Our sales force was able to increase face-to-face interactions with physicians during the third quarter, and approximately 40% of Sunosi interactions were in-person. We observed a 7% increase in U.S. prescriptions compared to the second quarter of 2020, including strong patient refills. Net sales were $9 million in the third quarter of 2020 and $20 million for the 9-month period and included inter-quarter variability in gross to nets. We continue to expect full year 2020 gross to nets in the 40% to 60% range, consistent with other analogs.

To expand Sunosi promotional efforts and reach the larger OSA prescriber audience, we have partnered with a contract sales organization to deploy 50 additional sales representatives dedicated exclusively to Sunosi. These sales representatives, each with over 10 years of experience, were hired and trained last month, and they're in the field, reaching customers starting today. These representatives will engage with 6,000 additional OSA prescribers. We are looking forward to expanding our reach and ensuring more HCPs make this important treatment option available to their OSA and narcolepsy patients. Additionally, we're making progress in bringing Sunosi to more patients around the world. We launched in Denmark last month, and we look forward to continuing the rolling launch to other European countries over the next 18 months.

Turning now to the oncology portfolio. I'm very pleased to give you an update on our launch of Zepzelca, which became commercially available in early July for the treatment of metastatic small cell lung cancer. Third quarter net sales were $37 million. Our launch efforts have been focused on the top prescribers, and we are seeing strong interest from physicians, reflecting the significant unmet need for new treatment options in small cell lung cancer, and in particular, Zepzelca's favorable product profile in this setting. During the third quarter, more than 800 accounts placed orders and approximately 80% reordered. There was a 70-30 split between community and academic centers, in line with our expectations. Based on early claims data from the first month of launch, we observed Zepzelca usage in both second line and third line and beyond settings. We expect there would be some initial pent-up demand in this 3 -- third line plus setting, and we anticipate that usage decreases going forward as more second-line patients are treated with Zepzelca. Zepzelca was included in the NCCN Guidelines in July, and last month, we received the NCCN promotional materials and began rolling these out to our health care audiences. We are extremely pleased with Zepzelca's robust initial launch performance. Lastly, we recently entered into a license agreement with PharmaMar for Canadian rights, and we look forward to bringing Zepzelca to patients in Canada as well.

Now turning to Erwinaze. Due to continued quality and manufacturing issues at PBL, the owner and sole manufacturer of Erwinaze, the product was only available in the U.S. market for one day in the third quarter. We expect significant global supply disruptions to continue for the remainder of the year, unrelated to COVID-19. Our agreement with PBL expires at the end of this year. We have the right to sell certain Erwinaze inventory post-termination. We expect to distribute available Erwinaze supply during the first half of 2021. Given the urgent need for a reliable and high-quality recombinant asparaginase, we are focused on bringing JZP-458 to market as quickly as possible. In summary, I'm extremely pleased with our third quarter and year-to-date execution across our portfolio, including the progress that we've made with new product launches. We look forward to continuing to deliver significant near and long-term revenue from an expanding diversified portfolio of durable and high-value programs as we bring multiple new medicines and indications to market.

I will now turn the call over to Rob for an update on our development programs.

Thank you, Dan. In the third quarter, we worked tirelessly to mitigate the impact of COVID-19 and made significant progress across our R&D portfolio, including the recent delivery of topline data from our JZP-258 in idiopathic hypersomnia, continued strong enrollment in the JZP-458 study as well as the reinitiation and completion of our healthy volunteer studies for JZP-385 and JZP-324.

I'm pleased that since the start of the third quarter, we have made 2 targeted additions to our early to mid-stage pipeline in areas of significant interest and unmet need. In September, we entered into a collaboration agreement with RedX for the discovery and preclinical development of 2 cancer targets in the Ras/Raf/MAP Kinase Pathway. This complements our pan-RAF inhibitor program and broadens our approach in this interesting and important pathway.

In October, we announced the acquisition of SpringWorks Therapeutics FAAH Inhibitor Program, which includes PF-04457845, which I'll abbreviate as PF-845, an irreversible FAAH Inhibitor that is Phase II ready. Consistent with our strategy to focus on life-changing medicines for people affected by conditions for which current therapies are lacking, we plan to initially focus this program on the potential treatment of post-traumatic stress disorder, PTSD, in patients with an adequate response to approved therapies. We expect to initiate a Phase II study in late 2021, following protocol development and global regulatory interactions. PTSD is a chronic disorder and a significant public health concern, for which there have been no new approved pharmacotherapies for nearly 2 decades. Current treatments include front line treatment for psychotherapy, 2 approved SSRIs and multiple other agents that are used off label to try to control symptoms. However, over 45% of patients are not well controlled and have residual symptoms.

With the underdiagnosed rate of PTSD, low treatment rates and significant number of patients with inadequate treatment responses, the U.S. target population of PTSD patients is approximately 2 million. Symptoms of PTSD, particularly impaired fear extinction, anxiety and sleep disturbances have significant negative effects on patients' ability to function and their quality of life. PF-'845 represents an innovative approach to treating PTSD with a novel mechanism of action that has the potential to address multiple core symptoms of the disease by enhancing fear extinction, reducing anxiety and improving disrupted sleep.

Based on clinical results from a healthy volunteer experimental model of fear extinction as well as the positive effects on sleep and mood observed in patients with cannabis use disorder undergoing acute cannabis withdrawal, there is a strong rationale to support the evaluation of this molecule in patients with PTSD. We are, therefore, really excited to be adding the FAAH Inhibitor to our expanding clinical stage neuroscience pipeline.

Turning to JZP-258. Last month, we were pleased to share the positive, clinically meaningful and highly statistically significant topline results from our JZP-258 Phase III study in adult patients with idiopathic hypersomnia. We are excited by the compelling results and the magnitude of improvement observed in the study. We are now fully focused on submitting a supplemental NDA to the FDA in the first quarter of 2021. We intend to bring this important therapy to patients as soon as possible with launch targeted in the fourth quarter of 2021. To this end, we were pleased that in September, FDA granted Fast Track Designation to JZP-258 for the treatment of idiopathic hypersomnia.

Turning to JZP-385, our highly selective modulator of T-type calcium channels for the treatment of patients with essential tremor. After a pause due to COVID-19, we made important progress in September, completing our PK study of an improved formulation. I'm proud that our team was able to efficiently and quickly restart and complete this trial while protecting the safety of the study volunteers, keeping us on track for initiation of a Phase IIb study in the first half of 2021.

Now to our oncology development program since starting with Zepzelca. We're actively working on the development program for Zepzelca in collaboration with our partner, PharmaMar, and supporting robust data generation and collaboration with external investigators. Areas of interest include evaluating Zepzelca, small cell lung cancer in combination with other therapies, in both the first-line and post-flattening settings; as well as exploration of Zepzelca in other tumor types. In the relapsed small cell cancer setting -- small cell lung cancer setting, in combination with immunotherapy, 2 investigator-initiated Phase I/II studies are underway, one in combination with pembrolizumab and another with atezolizumab. We expect to receive results of the Phase III ATLANTIS study this quarter.

Now moving to JZP-458, our recombinant Erwinia asparaginase. In the third quarter, we continued to enroll patients in our pivotal Phase II/III study. We were pleased that in September, FDA granted JZP-458 rare pediatric disease designation for the treatment of pediatric ALL, a further endorsement of the clear unmet need among patients with ALL -- pediatric patients with ALL. We are focused on bringing JZP-458 to patients as quickly as possible and remain on track with our goal to launch in the U.S. in mid-2021, following BLA submission as early as year end.

The Defitelio Phase II proof-of-concept study for prevention of acute Graft-versus-Host-Disease was completed, and the outcome of the study demonstrated a modest trend to earn a benefit with Defitelio, which is more pronounced in a subgroup of patients receiving anti-thymocyte globulin. The safety profile was consistent with previously reported clinical studies and continues to support the favorable safety profile of defibrotide. Following an evaluation of the full data, a decision will be made about any further research for the prevention of acute GvHD.

For Vyxeos, clinical data have been submitted for presentation at the upcoming American Society of Hematology Virtual Meeting in December 2020, including preliminary data from a Phase II clinical study being conducted by the University of Texas MD Anderson Cancer Center, evaluating Vyxeos in combination with venetoclax in relapsed/refractory or de novo acute myeloid leukemia.

I'll now turn the call back over to Bruce for closing remarks.

Thank you, Rob. We set out an ambitious range of transformative objectives for 2020 and 2021. I'm proud that through the flexibility, innovation and commitment of our teams, we are on track to deliver on our key objectives, despite the impact of the pandemic. I really want to thank our employees all around the globe for their incredible efforts this year. We are well on our way to executing 5 launches through the end of 2021, with 3 products already launched and 2 next year. JZP-458 is on track for launch in mid-2021, and JZP-258 for IH is targeted for launch in the fourth quarter.

We have made significant advances in our R&D pipeline and have also completed a number of corporate development transactions this year. And our disciplined and thoughtful management of resources, financial performance and liquidity will allow us to take advantage of additional strategic opportunities as they arise. Together, this gives us a strong and durable foundation and positions us well to continue to deliver significant improvements to the lives of the patients we serve as well as growth and value to shareholders. Thank you for joining us on the call today.

Kathy?

(Operator Instructions) With that said, operator, please open the line for questions.

(Operator Instructions) We do have a question from Brandon Folkes from Cantor Fitzgerald.

Maybe just on JZP-458, can you talk about if you remain confident that we will see interim data in the near term? And just what is the clinical path from here in terms of remaining on track to submit a filing by year-end?

Yes. Thanks, Brandon, for that question. I'll just point out to people that we have not said we will necessarily publicly release interim analysis data. What we have said is, we'll be looking at data along the way and that will inform our path forward with FDA. Rob, maybe I could ask you to comment a little bit on what lies ahead.

Yes. So we continue to work with the FDA on the appropriate data package and timing for BLA submission, and as we said in the transcript, where we continue to target a midyear launch with the potential BLA submission as early as this year.

Next one on the queue is Umer Raffat from Evercore.

First, congrats on the hypersomnia study. My question was, if you could speak, Bruce, to the size of the market? And perhaps, also remind us how many of current Xyrem patients are on -- are for hypersomnia indication? And on that note also, could you remind us, Bruce -- sorry, could you tell us if you believe if there is any real risk to the settlement structure you have on Xyrem post 2022?

So thanks, Umer. I'll take the second part of that question first. We entered a number of settlement agreements, and we're confident those are good agreements and don't have anything more to say at this point. Maybe I'll come to Dan for the question on the idiopathic hypersomnia opportunity and whether there is overlap with current treated Xyrem patients?

Yes. Thanks, Bruce. And this is some of the information we also gave last week on the Xywav teleconference. But in the U.S., based on claims data, which we think is probably in under diagnosis, there is 37,000 diagnosed IH patients. We also know that the majority of that diagnosis is generated by sleep doctors, similar to Xywav, Xyrem riders, really with a strong 90% overlap with 800 physicians. In terms of the question about how many IH patients are currently being treated with Xyrem, we think very few, based on anecdotes and what we know on a clinic basis. And even in the study where we had 140 or so patients, only a single-digit number had previous Xyrem exposure. So we really do think this will unlock a new opportunity for us, which has obviously got very close overlap with where we are, and it will also open up for an unmet need payer access.

Next one on the queue is Gary Nachman from BMO Capital Markets.

The Zepzelca number was very impressive in the third quarter. So just provide some more detail on the early feedback from physicians on the product. How they're initially using it in their patients? How much has getting on the NCCN Guidelines helped with uptake? And what is receptivity from payers been on pricing? And how has reimbursement been so far with Zepzelca?

Yes. Thanks, Gary. Maybe I'll turn it over to Kim to take this question.

Sure. Thank you. Yes, we are also very pleased and excited with the performance and the customer response to the launch of Zepzelca. Dan highlights one of the most important numbers there in terms of having 800 accounts having placed orders and 80% having them -- of them having reordered, and we do see a nice mix of business across community accounts and academic. Early -- based on early claims data that we looked at from the first month of launch, we're observing Zepzelca usage in both the second line and the third line and beyond setting and a nice, healthy portion of that in the second-line setting, which a is very positive indicator for us that prescribers see the value of using this product early in a patient's treatment regimen. We would -- did expect that there would be some initial pent-up demand in the third line and beyond setting and anticipate that, that group of patients is going to decline moving forward. In terms of reimbursement, we're very pleased. We're in a very strong situation. Payers have embraced Zepzelca, and there is really no issues on that front from a coverage and reimbursement standpoint.

Next one on the queue is Ami Fadia from SVB Leerink.

Congratulations on the nice quarter on the Zepzelca sales. My question is on the Xyrem, Xywav franchise. You talked about expecting some impact over the next couple of months as you gain coverage for Xywav. Is that going to be on the net realized price alone? Or should we anticipate some impact on volumes as well? And also in this context, can you talk about WAKIX? And is that -- if you expect to have any impact from that? Or if you think that, that product will expand the market?

Yes. Maybe I'll come to Kim first, just to talk about what's going on at the patient level, and then Renée, maybe you could comment on what people will see from a financial standpoint.

Just to clarify in the front part of that question, at the patient level, what is the specific question?

The question is that, are we going to see an impact on the net realized price alone? Or would you anticipate an impact on total patient number or volume as well?

So I'm -- sorry, I'm not understanding the patient part of the question.

I'll jump in, Kim. I mean as we said in the call script, we're working very hard to make sure all patients who want Xywav have access to Xywav and can transition on to the product. Renée, maybe I can ask you to take the piece on financials.

Sure. Yes. So we do expect through the payer access program -- sorry, the patient access programs that we've put in place that you will see as we have patients adopting Xywav, an impact to both the revenue bottle growth as well as an impact to gross to nets, and that's because of the different programs that are offered. So sub programs will come through such as couponing through gross to nets, and other bridge programs will come in the form of free bottles. So since we do report revenue bottle growth, you may not be able to completely connect what you're seeing in terms of revenue bottles in Xyrem versus revenue bottle growth in Xywav since the patient access programs will provide that smooth transition. Does that make sense?

That's very helpful.

And then maybe just to weigh in on your question about WAKIX, Ami. WAKIX has been on the market for some time now and the recent supplemental change to their label, including cataplexy, is really just a reanalysis of data that had been published and presented and was already out there. So we don't see -- we haven't seen much of an impact. If anything, having additional competitors in the market to grow the market, given the still relatively low diagnosis rate can be a benefit. And those patients who eventually come to oxybate, it's got a very unique profile, both for addressing EDS and cataplexy. And now with Xywav, we have the first and only low-sodium oxybate that we believe will be the treatment of choice for oxybate patients.

Next question comes from the line of David Amsellem from Piper Sandler.

So my question is surrounding Sunosi. I noted your comments about the contract sales organization and targeting more positions. I guess, the question here is, are you comfortable with the overall strategic direction of that franchise? And specifically, given the investment -- the significant investments in sales and marketing and focusing on OSA, is that appropriate given the trajectory of the product? And I guess what I'm getting at is that would a rare disease focus, in other words, exclusively a narcolepsy focus, may have made more sense? Maybe help me understand or help us understand how you're thinking about that product going forward.

Okay. Maybe Kim, I'll ask you to weigh in on this.

Sure. We remain very optimistic about the future of Sunosi. We've had very strong and favorable feedback from the prescribers and the patients that have utilized it. So we do believe that incremental investment in this product is going to pay off and be warranted. As Dan mentioned, right now, we're adding 50 additional sales representative. These sales representatives are very experienced, each with over 10 years of experience, where they were hired and trained last month. And they're going to enable us to reach an additional 6,000 OSA prescribers starting today that we haven't with our current sales force been able to reach. And we do believe that this will be an important investment for us. So we're looking forward to expanding our reach and continuing to bring this important medication to both narcolepsy and OSA patients.

Next one on the queue is Ronny Gal from Bernstein.

Congratulations on the bid this quarter, especially since it was not driven by Xyrem, but some of your other products. My question is on the payer dynamics for Xywav. Something you kind of said here spiked my ears, which is, you got coverage from your partner, ESI. But you still need to get coverage from the other large payers, despite some discounts you've already given this year on Xyrem. I was just wondering if you could just kind of give us a directional thinking here. As we think about the transition of the franchise to Xywav away from Xyrem, should we expect the net price per bottle to be lower by nontrivial amount. So this is not going to be a 2%, 3% decline, but something north of 10% or more. I know those contracts are not done, and you kind of want to be careful here in what you say, but just if you can just give us a directional call just so we don't kind of keep unreasonable expectations.

And second, you said on the call on Monday that you have made some deals to give you -- to give people access to Xywav through multiple pharmacies. And I was wondering if you can elaborate on this, and most importantly, does that mean that 340B pharmacies will now be able to dispense or at least, be the transition point for the orders on Xywav?

Yes. Ronny, maybe I'll take the second part of that first. So Xywav, like Xyrem, is still shipped exclusively from a single pharmacy, and that's for REMS-related reasons. So maybe I'll let Kim come back to the broader access question.

Yes. Sure. I think as we've mentioned on other calls, at the growth level, we have priced at parity, Xywav and Xyrem at parity. And really, our objective as we move into contracting is for the 2 products to be at approximately the same net level as well, of course subject to the payer negotiations that we have going on right now.

So I guess the question is versus your net price in 2020. As we think about '22 and beyond, should we kind of step down or you don't anticipate such a step down in pricing for the franchise?

Renée, you want to comment on that?

Well, we haven't given specific guidance for 2021 or 2022, Ronny. But what we have said is that we do expect our topline sales to grow in 2021, and we expect them to grow in 2022. And that by 2022, we would have nearly 50% of our revenues coming from our newer products for 2019 -- sorry, that have been launched from 2019 forward. So while we're not giving specific guidance for Xywav right now, we are looking to this diversified portfolio of products we're launching to contribute really meaningful to our revenue going forward. And we are expecting that growth at the top line for 2021 and 2022. And as you know, the oxybate franchise is a -- makes up still a large percentage of our revenues.

Next on queue is Jason Gerberry from Bank of America.

Question just for Bruce. Can you comment maybe what's going on with the supply situation with Erwinaze? $20 million probably the lowest value I've ever seen from this product. And it looks like a bit of a dislocation. And I realize you're kind of in a sensitive position with the unwind of the contract end of the year with PBL, but I think it's important for investors to think about the competitive dynamics that JZP-458 could be launching into next year. So can you provide any incremental color on perhaps what's going on with the supply situation?

Yes. Jason, good question. And the important thing here is to just separate in your mind, supply and demand. There is still absolute demand for Erwinia asparaginase, and we're doing everything we can to make sure we provide as much supply to the market as possible. It's just been erratic in terms of when we have lots that can be distributed and when they are available, they are dispersed quickly to help patients who need the product. So we think it's even more important than we would have said a year or 2 ago that we have a reliable, high-quality, sufficient capacity, more modernly manufactured product that will reliably meet the needs of patients, both in the U.S. and then overtime, in all markets. So we're doing everything we can. You're just seeing unpredictable availability of product and very limited availability of product.

Dan, anything you want to add on that?

Just each batch takes quite some time to work it through the quality system with the FDA, in particular, in the U.S. We do keep our customers as informed as we possibly can, and we have updated the supply website recently that we are anticipating a new batch available November 4 to 6. But it's going to continue to be sporadic, but we do see some product coming soon.

Next one is from Annabel Samimy from Stifel.

Congratulations on the launch of Zepzelca. That was great. Can you maybe give us a sense if there was any initial stocking into the channels? Or if it was all demand, specifically pent-up demand? And does that mean that there is going to be a decline next quarter? And if you could just give us a little bit of granularity of what the underlying demand represents in terms of patient cycles per patient, average price per cycle, just how that looks?

So Dan, do you want to jump in on this?

Yes. If you listen carefully to the script, what we were saying is, there was a bolus as we expected, third line, fourth line. And the good news was, there was some benefit for those patients, but it's really getting Zepzelca to be standard of care for relapsed second-line patients. And that's what we're penetrating into, and there is still plenty of room for growth. And so third line, et cetera, will fall off as more and more patients in second line have that exposure, but you shouldn't anticipate a quarter-over-quarter decline.

And any granularity on the cycles or patients or average price per cycle?

Not so much right now. I mean it's not like prescription data. It takes a little bit of time to collect the claims-based data. So we've got some window on July, and we'll have more as each month goes on. But anecdotally, we're hearing good uptake in both platinum-sensitive and platinum-resistant patients. And platinum-sensitive is where you expect longer duration of therapy as well as better prognosis and better chance for response.

Okay. So if I heard correctly, it's all bolus and not necessarily inventory?

Correct.

Correct.

Next one on the queue is Balaji Prasad from Barclays.

So following up on Zepzelca itself, just want to understand more about your commercial efforts right now, and how we should think about the cadence of accounts being converted as we think about the next couple of quarters? So currently, you're at around 800 accounts. When would you go for a broader reach?

Kim?

Yes. Really, we are calling on all the accounts and providers that we think are valuable. We're not starting with a subset. So really, what we're seeing in terms of demand, so Zepzelca is, I believe, driven by the patients that the accounts have ready to begin along with the awareness that we've created. So not looking to really expand that but to continue to try to educate and reach those accounts and generate awareness.

Next one on the queue is Akash Tewari from Wolfe Research.

So for 2021, I think Xywav estimates are about $280 million, and that's kind of implying a 50% switch from Xyrem to Xywav onto next year. You mentioned that some patients will wait for a new script before switching over. What percent of those late adopters make up that $1.7 billion of sodium oxybate sales right now? And what do you think about an implied switch cadence of about 15%?

And then just very quickly, on JZP-324, your slides mentioned today, it's still in Phase I. Where do we stand on enrollment and data readout for that program? And when would we know whether you're taking it to Phase III trials?

Yes. Akash, no update on 324 today. So we don't have additional information to give. On the Xyrem, Xywav dynamic for 2021, obviously, we have not given guidance for 2021 yet. We plan to do that in late February on our year-end call. The estimates that are out there didn't come from us. I think you heard the comments in today's call about we expect this adoption to Xywav to happen over time. We think it's important to educate both patients and physicians about the benefits of Xywav. Of course, from a financial perspective, whether we have patients on Xyrem or Xywav next year is not as big a driver of our financial results relative to 2020, as for example, Zepzelca or the 458 launch or the launch in idiopathic hypersomnia or growth in Sunosi and our other assets. So it will play out over time. We have set the longer-term goal of getting to a majority of all oxybate patients on Xywav in 2023, but we have not yet given a specific target for 2021.

Next one on the queue is Greg Gilbert from Truist Securities.

Back to 458, I think it's probably for Rob or for Dan to some degree. I just would like you to -- if you could confirm that all aspects of the 458 development trial are on track? And also, how quickly can you make product? And are you already making product to meet demand? And when can you begin to play offense in terms of looking at additional geographies and indications?

I mean, short answer for me.

Rob?

Yes, we consider the program is on track.

And Dan, do you want to talk about supply?

Sure. Yes, and that was a key factor. And working up the recombinant system is to make sure we've got a quality and modern process and we're already at commercial scale, and we have tens of thousands of vials actually that have been generated and would be available for commercial launch that were part of -- will be part of the regulatory package.

Does that mean you could meet all demand as soon as it's approved?

Yes, within reason, but yes.

Next on the line is Jessica Fye from JPMorgan.

For JZP-385, you completed the healthy volunteer study of the modified release formulation. Can you elaborate on the results there? And in particular, are you constant in the safety and tolerability of this molecule now?

Yes. Rob or Phil, do you want to take that?

Yes. Great. I can take that. Thank you, Bruce. Yes, so we've completed the study conduct, but we don't have the results yet actually of that study. And the goal of the modified release formulation was to have a product that could be taken once-a-day and be better tolerated, but we do not have results at this point in time.

Next one on the queue is David Risinger from Morgan Stanley.

So Bruce, I just wanted to ask you to basically paint a picture for how you see the 2023 timeframe? And the reason is that Jazz shares are trading at a high single-digit PE on expected 2021 EPS due to concerns about a feared Xyrem cliff. And I think it would be helpful for you to frame how you see the evolution of the company's financial performance as it faces Xyrem generics in a few years?

Yes. Thanks, David, and really good question. We're really focused on a couple of things to diversify the business over time. And while we have every intention of performing well this year and next year, a lot of what we're doing is designed to position us well in future years, including our goal to have about half of our total revenues come from newly launched products by 2022 and our goal to have a majority of all oxybate patients beyond Xywav in 2023. So you can think about that oxybate franchise as the first piece of value creation, which is how well do we do with Xywav, and continuing to grow the market as we've talked about with the potential of an IH launch next year.

The second piece is what do we do with the rest of our portfolio? How do we do with Zepzelca and Sunosi and 458 and other opportunities in terms of growing those and then bringing forth new products from our portfolio, including some mid-stage programs that we featured in today's call? But I don't want people to miss the third piece, too, which is continuing to put capital to work in broadening our opportunity set, both things like Zepzelca, where we did a deal and launched within months as well as things that are earlier in clinical development. And while they might not be on the market in a few years, could be generating key clinical data that will help people to value that pipeline. So I really feel like in each of those buckets, we're performing well right now, and all of those contribute, in our mind, to a sustainable growth strategy over the longer term.

Next question comes from the line of Graig from Goldman Sachs.

I've got two, if I could. Just one, we've seen Jazz from a BD perspective do some interesting earlier stage deals. And I'm wondering having added Zepzelca, which perhaps was more near-term in terms of revenue, how should we be thinking about BD would be looking to fill across the different developmental stages? Or is there more of a desire to focus maybe on the mid- or early-stage pipeline? So that's my first question.

And just on my second question, and as you think about new products such as the SpringWorks PTSD asset, how do you think about synergies from a commercialization perspective? So for PTSD, I don't know what the natural selling capability is, and whether you'd have to incrementally grow off of that. So just any thoughts on how you think about that from a BD perspective?

Great. I'll take that. That's -- this is Renée. Great question. So with respect to corporate development, our strategy hasn't really changed in the sense that we're continuing to look at highly differentiated durable assets that can provide meaningful clinical benefit for patients. As we think about then the stage of the pipeline, we are focused on different parts of the pipeline. So we -- you will probably see us continue to do some early deals as well as some mid-stage deals. Being able to bring in a Phase II ready asset in the FAAH Inhibitor for SpringWorks was a nice strategic asset for us to continue to fill out that mid-stage portfolio. But I'd say, we're also looking specifically at transformative transactions, where we could leverage up our balance sheet -- leverage our balance sheet, cash flow and infrastructure to acquire an on-market asset. We're looking at M&A as well, but as you know, those larger deal opportunities, they're just fewer in nature. So we're much more calculated in terms of how we think about what would be most strategically advantageous for us, and also, how do we most appropriately leverage our balance sheet in order to be able to take on something that can also enhance the durability that Bruce described with respect to the long-term diversified revenue base that we're trying to establish. So I would say, we're looking fairly broadly, both for pipeline augmentation and then also near and on-market opportunities where we could leverage that commercial infrastructure that we have globally to be able to continue to make it more effective and profitable from a financial perspective.

With respect to the commercial piece, we do think that when we look at PTSD, as Rob had described, this is a high unmet need area. We have capabilities internally where we've been focused on PTSD as an indication of interest. And while we would need to expand some of our commercial activities in order to support this in the future, we look at this as something that if we get through a Phase II study, and this is positive, then you can also build around that portfolio over time because there is such a large unmet need and a meaningful market opportunity.

And operator, the next question in the queue will be our last question.

Okay. So for the last question, we do have David Steinberg from Jefferies.

I have an additional question on Zepzelca. I wanted to drill down on some of the components of the $37 million you reported for Q3. Specifically, you highlighted the fact that one of the reasons for the really strong initial quarterly sales were pent-up demand in third and fourth line. And so -- but I don't recall that you gave us an actual split of second line versus the others. If not, could you give us that breakdown or some rough approximation there?

Yes. David, this is Bruce. I'll just come back and say, we have data from like the first month of launch that would help us understand where the product was used, and we don't have more recent data. So we really can't give you a for the quarter here was the percentage. As Kim said, we are seeing good use in second line and growth in the number of accounts ordering. So we feel good about where we are in the launch of this product as we continue to take the message out to the field. So really happy with how we're doing just a few months into a new launch.

And I would just have to wrap up my comments by saying, really pleased with how the company overall is performing across the commercial portfolio and making rapid progress on our R&D program. So I think we were pleased to give the update today. We've got a lot ahead of us with Xywav just launching today and some near-term submissions coming in 458 and on the IH side. So still a lot of work ahead of us before we finish the year, but a really great third quarter.

Okay. And there are no further questions on the queue. I will now turn the call back to Kathy Littrell.

Well, thank you, Sino. Thank you again for joining us today. We will be participating in the Jefferies Virtual London Healthcare Conference later this month and hope to speak with many of you. This now ends our call.

Ladies and gentlemen, this concludes today's conference call. You may now disconnect.