Hello and welcome to the Jazz Pharmaceuticals Full Year and Fourth Quarter 2020 Financial Results Earnings Conference Call. Following an introduction from the company, we will open the call to questions. I will now turn the call over to Andrea Flynn, Head of Investor Relations at Jazz Pharmaceuticals. You may begin.

Thank you. And thanks everyone joining the call. Today we reported our four quarter and full year 2020 financial results and provided our financial guidance for 2021. The press release and the slide presentation accompanying this call are available on 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 and Chief Medical Officer. Joining the Q&A 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, and Shawn Mindus, Senior Vice President, Strategy and Finance. 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 the 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 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. This communication is not intended to constitute an offer to buy or sell, or the solicitation of an offer to buy any securities, or solicitation of any vote or approval. GW intends to file a proxy statement with the SEC regarding the proposed transaction that will be mailed to GW shareholders. You should review material filed with the SEC carefully, as they will include important information regarding the proposed transaction, including information about Jazz and GW, their respective directors, executive officers and certain other members of management and employees who may be deemed to be participants in the solicitation of proxies from GW Pharmaceuticals security holders, in connection with the proposed transaction. Please also review slides two through five of today's presentation for other important information, including where you can find more information on the proposed transaction, and on the directors and executive officers of Jazz and GW. With that, I'll now turn the call over to Bruce.

Thanks, Andrea. Good afternoon, everyone, and thank you for joining us today. 2020 was an exceptionally productive year for Jazz, driven by the expertise commitment and capabilities of our organization, and defined by operational excellence across commercial and R&D. We entered 2021 in a position of strength. We plan to execute on significant milestones that we expect will further enhance the growth and durability of our business, and to accelerate our transformation as an innovative biopharma company. I'm very proud that from this position of strength and readiness, we announced earlier this month that we signed a definitive agreement for the acquisition of GW Pharmaceuticals. We're excited about the potential to add epilepsies, a third high growth commercial franchise, to our business, with Epidiolex, a potential near term blockbuster, as well as GW’s robust neuroscience pipeline. The combined company would be a leader in neuroscience, with a global commercial and operational footprint, and we expect this transaction to deliver substantial shareholder value. We are excited to be joining two companies with a shared culture, built around the same mission, innovating to transform the lives of patients. In 2020, we demonstrated the resilience of our business and our agility, innovation, and execution capabilities across the company despite the pandemic. We launched important new treatment options for patients, including Zepzelca and Xywav in the US and Sunosi in Europe, delivered robust revenue growth, and generated significant value for shareholders, successfully advanced early and late-stage clinical trials, and added multiple new innovative products and targets to our expanding pipeline. Our R&D organization initiated regulatory submissions to FDA for JZP-458 in acute lymphoblastic leukemia. Under the real-time oncology review in December, and completed the rolling sNDA submission for JZP-258 in idiopathic hypersomnia this month, which positions us for two more potential product launches in…

Thank you, Dan. In the fourth quarter, we continued to make significant progress across R&D, including initiating the BLA submission of JZP-458 under real-time oncology review for patients with acute lymphoblastic leukemia and lymphoblastic lymphoma, initiating the rolling submission, sNDA submission of JZP-258 in patients with idiopathic hypersomnia in December, with completion of this submission this month. We have also continued our efforts in geographic expansion for key products, including Defitelio, Vyxeos, Sunosi and Zepzelca. I'll start with an update on the progress in our neuroscience portfolio. Starting with JZP-258, we are looking forward to the presentation of our Phase 3 study results in adult patients with idiopathic hypersomnia at an upcoming medical conference in second quarter 2021. We're excited by the compelling study results we observed and look forward to sharing this data. Under Fast Track designation, we prioritized the rapid initiation and completion of the rolling sNDA submission to FDA within approximately four months of announcing our topline data. As we work to bring JZP-258 to patients with IH as soon as possible, a debilitating disorder, for which there are no approved treatment options. Turning to JZP-385, for the treatment of patients with essential tremor, a progressive, irreversible and chronic debilitating disorder that profoundly impacts quality of life. In 2020, we completed our healthy volunteer study and we anticipate initiating our Phase 2b trial in mid-2021. Moving now to JZP-150, an irreversible FAAH inhibitor, which we are initially investigating in post-traumatic stress disorder. We plan to initiate our Phase 2 study in late 2021. I'm excited to get both JZP-150 and JZP-385 into important clinical trials this year and move a step closer to helping these patients suffer significant impacts to their quality of life and for whom there are limited parent treatment options. Now, turning to our…

Thanks Renée. [Operator Instructions] So with that said, please go ahead and open the line for Q&A.

[Operator Instructions] Our first question comes from the line of Jessica Fye with JPMorgan. Your line is open.

Hey guys good afternoon. Thanks so much for taking my question and further color on the Xywav launch. I was wondering if you could say how many active patients around Xywav currently.

Jess, this is Bruce. We're not going to give intra-quarter data like that. We'll obviously up update again on our next call. But our body language here is we're really pleased with the way launch is going, not just during the first couple of months, but as we continue through today.

Great. Thank you.

Thank you. Our next question comes from the line of Amy Fadia with SBB Leerink. Your line is open.

Hi, good morning -- sorry, good evening. Thanks for taking the question. Can you talk about out of the patients that are on Xywav, can you talk about what peers have been requiring as a requirement for switch? Are most of these patients are patients that have comorbidities or are you seeing a fair mix of patients that may or may not have comorbidity?

Yes, maybe I'll ask Kim to weigh in on this one.

Sure. So, we're very pleased, obviously, with the progress that we're making here on the launch, our focus here on the launch is on transitioning Xyrem patients to Xywav, we really are seeing that the vast majority of those patients are experienced on Xyrem in terms of the patients that are on Xywav. But both in terms of having just taken Xyrem or have taken Xyrem in the past. But we also see a portion of patients who are new to oxybate overall and new to Xywav. So I'm very pleased that it's been consistent with our strategy. And I think that you have a question about payer coverage, I'm just trying to clarify that.

Yes. So, with regards to the payer coverage, I'm trying to understand how you're placed on the plan? And what might be certain criteria that payers are requiring physicians to address before allowing patients to switch from Xyrem beside or a de novo patient being allowed to go in Xywav.

Thank you. So, I think, as you know, we've stated, we've had basically a parity strategy between Xyrem and Xywav both in terms of our pricing strategy and our goal of pricing not only at the gross level, but also at the net level, the two products at parity. But also in terms of how the two products are treated ultimately on the on formulary, we're looking for Xywav to be placed on formulary in a comparable position to that that Xyrem enjoys today. And within that means also not just where it sits in terms of the tier, but how it's treated in terms of utilization management. And so far to date, we're very pleased to say that with the contracts we've signed, we are achieving that goal of parity treatment.

Okay. And if you don't mind, just a final point on that, out of the patients that have been switched to Xywav, up until the end of the year, can you talk about whether or not the mix of patients from that subset that may have other cardiovascular comorbidities or not?

Yes. Dan, maybe I'll ask you to weigh in on that one.

Yes. Thanks, Ami. Yes, just -- we're positioned, and we're actually pleased with the uptake. In the offices that are adopting that really all patients who are on oxybate therapy, lifelong treatment, modifiable risk factor whether or not they have current comorbidities, they're at risk of it. And so we're seeing a broad cross-section of patients. We're also seeing some new patients, obviously, coming on where the suite of access services enables and the rising payer coverage with more than 60% of commercial lives covered, coming on to Xywav initially for oxybate therapy versus Xyrem. And we also think over time, we're going to find patients who had previously not been candidates for Xyrem coming into therapy as well in addition to growing into the IH indication. So very pleased with the uptake. Certain physicians were further along in the journey at the time of launch and understanding the risk factors and the amount of sodium. In Xyrem, some physicians were not and also the patients become an active part of this dialogue as well.

Thank you. Our next question comes from the line of Jason Gerberry with Bank of America. Your line is open.

Thanks, and thanks for taking the question. So Bruce, I appreciate the commentary about favorable body language on the Xywav switch. What I was wondering is, is the switch trending ahead of your expectation? I know you put out some metrics for where you expect it to be in 2023. But just curious if you're operating ahead of expectation, or if we should consider there to be a pent-up bolus. I would assume maybe only 20% of patients have seen probably their doctors since the switch occurred. So I'm a little surprised how high the number was. So just curious if you can provide any commentary there, because I think that will help us think about the progression over the course of the year? Thanks.

Yes. I mean we're -- Jason, we're still early in the launch. But to directly answer your question, we are ahead of the expectations we had set internally for the first couple of months. And I think as you heard Kim and Dan comment, our messaging is resonating with people about the benefit of this therapy and excitement about it. And so I don't think of this as a bolus that adopted early, we see continued interest and look forward to continuing our educational efforts over the balance of this year. And next and continuing to work toward our goal of this being the primary brand in the oxybate space even out in 2023.

Got it. Thank you.

Thank you. Our next question comes from the line of Ken Cacciatore with Cowen. Your line is open.

Thanks so much. Bruce, as we stare at the Xyrem and Xywav franchise, it's kind of a really fascinating modeling exercise as we look at 2023. Obviously, you have Xywav, which could be taking a vast majority of the franchise. And then you have information about the settlements and who can come and the kind of the volume they can supply. And you also know the royalties that they owe back to you. So as we look at 2023, and we try to take all these individual pieces of kind of significant conversion to the franchise and then your knowledge of what could be the generic supply for Xyrem, and again, what they owe you, can you help qualitatively maybe talk through a little bit of either any enthusiasm you have or how we can start thinking about? Maybe a preservation that some of us have modeled a little bit too negatively? And then I just wanted to follow-up on the commentary you made on Erwinaze in 458. I would assume that you all understand the supply that you're not able to put into the marketplace? I would think that information is almost perfect. So can you maybe give us a sense of what we are unable to supply and therefore, what we may be able to supply with 458.

Yes. Thanks, Ken, and maybe I'll take the first part of the question around oxybate and ask Dan to weigh in on asparaginase. In terms of oxybate, the way we're thinking about this is, we've got a great growth opportunity in front of us. We're seeing continuing growth in diagnosis and initiation of therapy on oxybate. That's a continuing trend we've had for a number of years now. We see an opportunity with Xywav to address some patients whose physicians were unwilling to start them on therapy, historically due to high sodium load. We see an opportunity, obviously, with idiopathic hypersomnia. Upon the approval and launch of that product later this year and that's a substantial opportunity relative to the size of the narcolepsy population. So we see growth opportunity in front of us. As you go out a few years, we do expect there will be authorized generic competition beginning in 2023 or potentially earlier in some circumstances and as we've disclosed, we have economics, in some cases, substantial economics in those authorized generics, which we distributed through our rents. But to be clear, we think that most patients in this lifelong therapy in this group, known to have high cardiovascular risk will benefit from the advantage of Xywav therapy. So we see the opportunity to expand the product and then really to be a continued preferred treatment far out into the future. Dan, do you want to take asparaginase?

Yes, Ken, on your question about asparaginase. I mean, we don't have perfect information in the sense that we've been supply-constrained for 4 years. And probably last year was our worst year in terms of supply capacity to the U.S. market. And so as that happened, we've cut back completely on promotion and ISTs and clinical work. We've also put in sort of patient-by-patient verification for product supply. So no inventory sits on the shelves at the hospitals. And we haven't sort of penetrated into certain new geographies like Japan or really helped with the promotion of asparaginase containing regimens for adolescent and young adults. So before we were supply constrained, we were moving above $200 million in product sales, that was several years ago. We believe there's substantial room for expansion with a high-quality, fully recombinant product that physicians can count on that when they start the course of therapy, they can get to the end of therapy and ensure the really successful treatment outcomes that they currently have with asparaginase.

Thank you.

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

Hi. Good evening, everyone, and thanks for taking the question. Maybe just on Xyrem, with the pace of conversion that we are seeing, Xyrem may soon become a mood point, but want to get an update on Avadel. It's been two months since they've filed. What is your strategy now? And if FDA accepts their filing, is there any way for you to still mandate that there’d be a Para IV -- considered Para IV? How do we think about the impact of this, especially next year? Thanks.

Yes. Thanks for the questions. We're not going to do any disclosure on behalf of Avadel. We'll keep people posted on where they are with FDA. We'll remind you that, we do believe they should need to Paragraph IV certify against Orange Book listed patents on Xyrem, that have to do with the safe distribution of the drug, both as regards our distribution system, which ensures safe use of the product and limits abuse, misuse and diversion as well as, helping patients understand an important drug-drug interaction. That Paragraph IV certification can happen on submission, but it can be required at any point during the review process as well. And then, of course, we have what we believe is relevant intellectual property and we'll defend that in the best way possible for Jazz.

Thanks, Bruce.

Thank you. Our next question comes from the line of Randall Stanicky with RBC Capital Markets. Your line is open.

Great. Thanks. Bruce, how are you guys thinking about total oxybate volume growth for 2021? And specifically, we're hearing from physicians that there's an expectation of a big pickup going forward in oxybate patient volumes. And I'm trying to understand if that's consistent with what you're expecting? And then how much of that would be related to the lifting of COVID headwinds, versus the onboarding of new high-risk patients, coming into the patient pool, or even just you being out there more aggressively educating physicians around Xywav and detailing the product? Thanks.

Yes. Maybe I'll start, and then I'll ask Dan if he wants to add. In general, Randall, I'd say this is a really exciting period for narcolepsy patients, with the additions to Xyrem as a standard of care, the addition of Sunosi as a new wake-promoting agent, pitolisant coming to market, now with Xywav coming to market. There are treatment options that weren't available before. There are more people out talking to doctors about appropriate diagnosis and treatment options, and that's good for patients. And if that leads to either more diagnosis or more treatment, that would be really helpful, since narcolepsy is still an underdiagnosed and undertreated disease. In terms of our growth expectations, we know that COVID-19 had an impact. We think that impact is lessening, as we move through 2020. And we, like the rest of the world, are hopeful that 2021 will turn out to be a better year in terms of patients being able to access medical care and get appropriate treatments. We're excited to be promoting a new product. And as we head toward the end of the year, look forward to a launch in an indication with no currently approved therapy. Dan, any color you want to add?

Yes. I just add on to what you said, say, persistence and compliance is something we did see pickup during COVID, but the headwind was, of course, the diagnosis of patients, and that's been definitely impacted again in the fourth quarter with COVID. So -- and narcolepsy still remains pretty underdiagnosed. The other thing in terms of growth will be just patients as they're becoming aware of the treatment option, whether they had tried Xyrem and come off or hadn't tried it before knowing there's sort of a longer term, healthier treatment option. I think the patient will play part of the journey and reaching the patient is going to be important to us. And then lastly, I would say there's patients who clearly were salt sensitive and not candidates who now Xywav provides a therapy for them and also significant expansion into the idiopathic hypersomnia market where there's no FDA-approved drugs and the managed care has made sure that oxybate has not been widely available for those patients.

Bruce, are you able to share a volume growth number?

No. So, we provided a neuroscience net sales guidance for the year, which has the puts and takes of Xyrem's, Xywav, and continued Sunosi growth both in the US and ex-US, but we're not giving a specific volume growth expectation. Obviously, as we move out into the very end of the year and next year with a successful IH launch, we expect that there's opportunity for the kind of volume growth we haven't seen in recent years.

Thanks guys.

Thank you. Our next question comes from the line of Gary Nachman with BMO Capital Markets. Your line is open.

Hi guys. Just follow-up on last question. [Technical Difficulty]

So Gary. Unfortunately, that was garbled. I was trying to pick out enough words, but I could answer a question that was related spot you asked, but I'm not sure what you asked. So, I don't know if you get a better connection.

Could you hear me now?

That's better.

Okay. [Technical Difficulty] just anything potentially this year in the guidance and just how you're preparing to launch the indication into the market. So, now that you've had a lot more time to think about the overall opportunity, just give us a better sense of how you're going to be going after that once it's [Technical Difficulty]

I know you were asking about the launch. Was that idiopathic hypersomnia or JZP-458?

No, it was idiopathic hypersomnia. I don't know why -- I'm sorry for the connection, bad connection. Yes. Just -- yes, do you have more time to think about it, the overall opportunity and if it's in the guidance for this year, if there's anything baked into the latter part of this year once it's approved?

Yes. Maybe I'll start with the last piece, which is there would be very little in our guidance for 2021 because the launch would be happening towards the very back-end of the year. It will take a little while to build awareness as you know, as you're seeing with the launches of Sunosi and Xywav, you don't necessarily have perfect coverage day one. So, I wouldn't think of it as a major revenue contributor this year. Although we'd love to get some patients on therapy. Maybe we could just ask Rob to jump in for a minute and just talk about -- Rob or Phil, just talk about idiopathic hypersomnia as an opportunity from a medical standpoint. And then Kim, maybe a few reflections on launch?

Phil, why don't I have you go first, and I'll join in as needed.

Great. Thank you, Rob. Yes. So I think as we've understood this population more and more, we clearly understand that this is a chronic disabling disease and these patients have a lot of -- not only excessive daytime steepness, but also a lot of dysfunction as a result of that excessive daytime sleepiness have a lot of sleep inertia. I think we've talked to you about that before. There are a lot of difficulty waking up and have very long sleep periods in many cases. As we've understood this more and more, and we see the benefits from our OED study, we recognize that we can treat many of the symptoms associated with this chronic disabling disease. From our team's databases, we're aware as I think we've shared before that we have about 37,000 patients from patient’s data bases. But we've also heard reports from a number of key opinion leaders who are also prescribers of the narcolepsy population that they see a large number of these patients that have ranged from anywhere from up to a similar number from anywhere, I think, from 10% up to 80% to 90% of a similar population in size to the narcolepsy. So we haven't completed all the EPI data around this. I think we'll continue to do that. We just know within the health claims databases. We think it's going to be a sizable opportunity. And I think when we have a chance to share all of the data at the upcoming meeting that Rob alluded to in the second quarter of this year. The data is really compelling, and I think will be -- resonate very well with the prescribing population for this target population.

And just to pivot quickly over to launch planning. We've got a team ready to go, obviously, significant overlap with the physician audience. We've already got relationships with and are educating about Xywav therapy. We think there's a significant number of under diagnosis, but the current diagnosed patients from a chart poll was 37, 000. So that's a big opportunity to start with. And then very importantly, we do have our clinical data from the Phase 3 that has been accepted at an upcoming medical conference in Q2. Really pleased to not only having statistical significance, but really clinically meaningful data in terms of the endpoints. And that will be shared six months ahead, and that's great as part of the medical education in advance of the fourth quarter launch.

Okay, great. Thank you.

Thank you. Our next question comes from the line of David Amsellem with Piper Sandler. Your line is open.

Thank you. So just another question on IH. So, the contracts that you have in place right now, is that going to apply to IH patients? I mean, just maybe give us some clarification on how broadly applicable those contracts are as you think about the IH launch? And then a longer-term question is, with the orexin agonist in development, how do you think about the potential impact on the footprint of oxybate in general to the extent that one or more exons get commercialized?

Yes, David, on the first part of the question on contracting, we've certainly done our contracting with a view toward the evolving narcolepsy treatment landscape. But to your question narrowly, we do need an approved label and have conversations with payers about that before we're done. So no, it's not a fail to complete.

And then on orexin, maybe I'll ask Jed or Phil to just weigh in a little bit about the potential of orexin vis-à-vis oxybate?

This is Jed. I'll jump in. I think it's fair to say that everyone is excited about the potential for orexin agonist -- to be helpful in the treatment of narcolepsy. The mechanism or ex an agonist is substantially different from the mechanism of oxybate. And we anticipate the orexin agonist will likely have an impact -- pharmacodynamic impact that's similar to what we see with weight promoting agents and stimulants. And so, we expect that long term, those agents would be complementary to those potential recognizes with the complementary to oxybate in treating narcolepsy.

Okay. Thank you.

Thank you. Our next question comes from the line of Greg Gilbert with Truist Securities. Your line is open.

I hadn't thought to ask Jed a question, but since he's got the mic, maybe you could offer any thoughts you have on cannabinoids and sleep? I'm guessing you have some thoughts there. But my other question was for Renee. When you closed the GW deal, do you provide updated guidance right on the back of that or the next scheduled quarterly conference call, maybe you could just set the stage first on what and how you will guide? Thanks.

Yes, I think in interest -- in the interest of time, I'm going to suggest we not take the cannabinoid and sleep question right now. We'll have more to say about the combined neuroscience pipeline at closing, but I'll let Renee take your guidance question. Renée Galá: Yes. Thank you. And as you can appreciate, we're still working through getting to close of the transaction. And so once we actually close the transaction, and are actually running the business, then we'll have a much better feel for the timing of the guidance that we'll provide for the combined company. We will certainly provide updated guidance to reflect Jazz combined with GW post close, but the exact timing of that is a little early to say.

Thank you. Next question comes from the line of David Risinger with Morgan Stanley. Your line is open

Thanks very much. So management had hosted a very compelling call on the risk of high salt intake last year, and it seems logical that most doctors and patients would opt for Xywav instead of Xyrem, and that should potentially drive a faster-than-expected switch. But my question is, how would you characterize the risk of potentially triggering an early Xyrem generic entry in 2022, before you have a full year to drive Xywav adoption in idiopathic hypersomnia. Obviously, the current assumption is, the IH launch occurs at the end of 2021, I believe. And then the generic entry against Xyrem is in January of 2023. So if you could just provide some perspective on that, that would be helpful. Thank you.

Yes. Good question, Dave. And let's just say, we want to help as many narcolepsy patients as possible with Xywav. We are not holding back in any way. If we're so successful that we've triggered earlier ag entry, that is a success scenario from our standpoint in terms of our progress with Xywav. Specific to the IH launch, we did our studies with JZP-258 or what's on the market as Xywav and the IH indication would be specific to that product.

Thank you.

Thank you. Our next question comes from the line of Brandon Folkes with Cantor Fitzgerald. Your line is open.

Hi. Thanks for taking my questions. Congratulations on another good quarter. Maybe just changing gears a little bit here and focusing on Zepzelca, another good quarter there. Can you provide some color in terms of how much pent-up demand are we still seeing in third and fourth-line versus pure second line? And I know you mentioned that both Pat incentive and plate resistent are growing using usage. Any way to parse that out a bit more just in terms of the uptake between sensitive and resistant? Thank you.

Yes. For Zepzelca color, maybe I could ask Kim, to just talk a little bit about what you're seeing in terms of how the launch is progressing.

Yes, sure. So we remain very pleased with the response to the launch among the small cell lung cancer treating community, feedback to the profile and what they've seen in their patients has been quite positive. And as you see there, we're seeing nice growth in the product overall. What I can tell you is, that we're seeing growth through December, the data that we have across all patient types, including second-line, as you said, in both types of second-line patients in terms of platinum-sensitive and platinum resistance. So I think we're still in a stage where physicians are getting experience with it and are seeing a tremendous unmet need, a strong profile and still using it across a broad spectrum of patient types.

Okay. Thanks. And are we still seeing usage from certain fourth line patients as we saw last quarter?

Yes, through the data that we have, we're still seeing strong usage there.

Great. Thank you very much.

I will say our goal is, over time, to have this become the standard for second-line small cell lung cancer treatment and to have patients get it at that point. Obviously, that hasn't been true in the first few months after launch, right, because we’re establishing awareness, but overtime we’d expect that second line share to go up and therefore, to see less usage later. Of course, in second line, we'd expect longer duration of therapy as well.

Thank you. Our next question comes from the line of Esther Rajavelu with UBS. Your line is open.

Hey there. Thank you for the question. So, two for me. One on JZP-458. Dan, you mentioned that you've been somewhat out of the market with this product. So, I'm wondering, as you're preparing to launch 458, if you can help us understand how we should be thinking about the launch trajectory compared with where Erwinaze sort of left off? Or leaves off in the middle of the year?

Dan, you want to take that?

Yes, I think I'm going to punt on that question. I mean, we're going to give more detail as we've got precise launch timing and launch label and frankly, also know what's the asparaginase market look like in the US, but we do see opportunity for growth from where we've been clearly across all the categories I referenced. But I'd say stay tuned a little bit longer on anything more precise.

Great. Okay. And then for 385, you talked about tremor, tremor as an attractive opportunity boost before. And I think you just mentioned on the call that you've had some Phase 1 healthy volunteer data. So, can you give us some context of the data that you've produced for 385 versus what's been in the public realm in the past?

Yes. So Phil or Rob, do you want to jump in on that?

Sure, I'm happy to, Bruce. This is Rob now. The proof-of-concept Phase 2 study was conducted before the acquisition. It was done with a formulation that was fit for purpose. And so our initial steps was to develop a once daily formulation that could be commercialized, and that's what we refer to as the healthy volunteer study, and that will be taken forward into the pivotal Phase 2b study that we referenced earlier.

Thank you. Our next question comes from the line of David Steinberg with Jefferies. Your line is open.

Thanks. I know you've taken several questions about the Xywav switch, but just want to see if we could get a little more granularity. So, if you take the number of patients that were on oxybate therapy that you gave out at the end of the year as well as those you mentioned were active Xywav patients, you get about a 12% switch rate. And I know it's not that because you mentioned there were some newer patients who come in. I was just curious on the non-most recent oxybate switches how many -- or what percent of those new patients were just natural evolution of newly diagnosed narcolepsy patients and which were patient who previously redeemed not being able to be on Xyrem simply because they had cardiovascular issues or comorbidities. And then related to the patients with severe cardio issues, who previously could not be put on Xyrem. Some of the KOLs we've spoken to think there's a very small percent and others up to 20%. I'm just curious from your own research, what would be that theoretical number of patients who have severe enough CV issues that previously could not be put on Xyrem? Thanks.

Yes, Dave, a couple of good points there. You keep using the word switch. I would just remind you that we -- as you said in your question, we've got patients coming to Xywav, in some cases, directly from Xyrem; in some cases, from prior Xyrem; in some cases, new diagnosis; in some cases, their physicians may have not felt they were good oxybate candidates with the high sodium product in the past, even though they were diagnosed. And so it's a variety at the beginning as we would have expected prior to launch, we are seeing a majority of the Xywav starts come from patients with Xyrem experience. That's not a surprise to us. On the exact size of the opportunity of patients who didn't receive Xyrem historically because of those concerns. I'm not sure we have any better hard data to give you other than it's a significant population. But we see, like you do, varied estimates on that, and there's no precise way to track that.

Thank you. Our next question comes from the line of Annabel Samimy with Stifel. Your line is open.

Hi. Thanks for taking my question. So I just want to ask about Zepzelca for a minute. I know that you have to do a confirmatory trial and that you're still in discussions with FDA. Is there any color that you can provide on a type of trial that you might consider for Zepzelca, whether it be combination or anything else? And then on the sodium oxybate franchise, obviously, the pricing parity has helped, I guess, accelerate contracting a bit, and you're already a pretty -- at 60%, so pretty good. Do you expect this to continue to proceed rapidly or faster than average? And what can we assume for timing of I guess, net price normalization where you're not providing as much patient assistance as these payers get the drug on board and start reimbursing regularly? Thanks.

So I'll take the second question first and then maybe ask Rob to talk about where we're going with Zepzelca additional study. On the contracting, when we say we've got contracts in place for 60%, that doesn't necessarily mean all the rest are not revenue bottles. I know I used a double negative there. But that doesn't mean, we aren't getting paid for some of the others. It's just we don't have contracts in place. And our goal at the time of launch was we said within six to nine months of launch. Launch was in November, we still feel comfortable with that. Sooner is better, but we want to put in place sensible contracts. So it's quality over speed to make sure we've got good access for patients going forward. Rob, you want to talk about Zepzelca?

Yes. I would just mention that we, so far, have only had a very preliminary discussion with FDA where we presented the ATLANTIS data, and we expect to have a more meaningful discussion on what's -- what would constitute a confirmatory data package sometime in 2Q. So no further details really to offer on that, I would say that we have disclosed that we're very interested in evaluating Zepzelca in first-line extensive stage small cell lung cancer, and that would be a switch maintenance design, where we'd be adding on to existing therapy. So in the maintenance setting, it would be an immunotherapy, plus or minus Zepzelca versus immunotherapy plus placebo for example. I also would mention that we are -- we do have an observational Phase 4 study that's intentionally designed to gather additional useful information in the second line indicated setting.

All right. Thanks.

Thank you. Our next question comes from the line of Graig Suvannavejh with Goldman Sachs. Your line is open.

Hi. Thanks for taking my question. Congrats on a really nice quarter. Maybe I'll ask a different question that has to do with your BD strategies going forward. Clearly, the last 12-plus months or so, you've executed on a number of nice deals and it's kind of changed the trajectory of the top line. And with that in mind, given the size of the acquisition, what should we be thinking about in terms of BD and whether it's a priority over the next 12 to 24 months, you have a quite robust pipeline and you're integrating a fairly significant acquisition. So we'd love to get any color there? Thanks so much. Renée Galá: Sure. Graig, this is Renée. I'll take that one. So granted, the GW transaction is a meaningful transaction for us that we're very excited about. We've talked for a while about the potential opportunity to do a transformative transaction to be able to accelerate our strategy. And we've lined up financing that we think still gives us adequate flexibility to both invest in our important product launches, invest in our pipeline and then invest in additional business development transaction for the right asset. We still see plenty of opportunities to continue to add to expand the pipeline, both in neuroscience, as well as in oncology because you see we have quite a few things we brought into the pipeline, and we want to continue to focus on bringing in both differentiated assets and then building a durable business.

Thank you. Our next question comes from the line of Akash Tewari with Wolfe Research. Your line is open.

Hey guys. Thanks so much. On Xywav, have you heard anything back from the FDA on your application for orphan drug exclusivity for narcolepsy? And additionally, if you do get the OTE, what would that mean theoretically for the Avadel product? Additionally, do you have any updates on your once-nightly program? I know it looks like your Phase I trial should have read out by now? Thanks.

Yes. So no particular updates on either. As you know, FDA does not have a particular clock there on when it comes to ODE. So we're waiting to hear on that. That should become public once it's decided, and I won't speculate on impact on Avadel. You can ask them that question. And I forget the second part of your question. Once-nightly, yes. So we have not said more about our once-nightly development program, although it continues.

Thank you. Our next question comes from the line of Ronny Gal with Bernstein. Your line is open.

Hey good evening and thank for fitting me in. Bruce, I wonder if you can share with us whether the payer equipment that you have on Xywav and Xyrem give you preferred position versus other oxybate drugs? And then to the extent you chose not to take that one, I was wondering if I can ask you about the share of prescribers who have not used Zepzelca yet?

Yes. So on the first one, we're trying to ensure patients have good access to what we believe is a really important treatment option in Xywav. In general, that means we want them to have reasonable a ways to get treatment with appropriate diagnosis and in some cases, having tried other therapies. But essentially, it's not different from what we've had with Xyrem for a long time. And then on Zepzelca, happy to have any of my colleagues jump in on -- for those docs who have not yet used Zepzelca in second line, what your expectations are there.

Thank you. I'm showing no further questions in the queue. I would now turn the call back to Andrea for closing remarks.

Thanks all for joining us.

Maybe just before I flip it back to Andrea, just to say, thanks to the team at Jazz for really an incredibly productive 2020. And I hope all of you on this call take away that 2021 looks like another exciting year with lots of product launches, lots of clinical progress, excitement about the GW transaction and what that can mean for Jazz, for patients, for employees and for our shareholders. We've got a lot ahead of us and hope to continue executing exceptionally well. Andrea?

Thanks, Bruce, and thanks, everyone, for joining us today. We'll be participating in the upcoming Leerink and Cowen virtual conferences and we hope to speak with many of you then. This concludes our call.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.