Jazz Pharmaceuticals plc (JAZZ) Earnings Call Transcript & Summary

Great. Welcome back, everyone, as we continue the 2021 JPMorgan Virtual Napa Valley Biotech Forum. We're continuing the day sessions with Jazz, and I'm joined by a number of members of the management team, including the company's Chairman and CEO, Bruce Cozadd; Head of R&D and Chief Medical Officer, Robert Iannone; Chief Operating Officer, Dan Swisher; as well as Andrea Flynn, who heads up IR. [Operator Instructions] You can use that as the session is going to send any questions through the portal, I can ask them to management. There's a little lag on that. So feel free to just send them as you think of them while we're going, and then I'll ask management. So before we get into Q&A, Bruce, maybe you can just start with a couple of opening comments to kind of frame the conversation, and we can take it from there.

Yes. So Jess, great to be with you. And Dan, Rob and I are really excited to update everyone on what's going on at Jazz. I think most of you know, we're in the midst of a really busy 2020 and 2021 with 5 product launches, 3 of which we accomplished last year, 2, upcoming this year. And now the pending acquisition of GW Pharmaceuticals. And really in the now 19th year of Jazz's history, this is the most transformational period as we grow our revenues, diversify our revenues and continue building a really robust pipeline that we think will fuel sustainable growth. So, excited to hear your questions, Jess.

Great. Well, maybe before we get into some kind of specific topics, I was curious if you could just open up -- I'd love to hear your view on where do you think some of the larger disconnects are between your view of the Jazz story and the view that you perceive most investors hold.

Yes. In terms of any disconnect, I think it's just people keeping up with the rapid evolution of the story. If you look at what's driving excitement about Jazz right now, a lot of it is around our Xywav launch and how that's progressing and the upcoming opportunity to expand into idiopathic hypersomnia. And I think that's a pretty big change from how people were thinking about our oxybate business even a year or 1.5 years ago, right, in terms of now this growth and durability we have in the oxybate franchise. The second thing I would point to is just that further diversification of our revenues, including with the Zepzelca launch and the upcoming JZP-458 launch. So as the composition of our revenues and our growth sources change. And then the third piece is, we've been saying for a long time, we put our capital to good use and be able to do some acquisitions, some licensing to continue to broaden our portfolio, and GW Pharma clearly does that but that's a relatively new piece of the story, too. So how we took north of $2 billion off our balance sheet and used our strong cash flow to now turn that into a third commercial franchise in Epidiolex and a broad neuroscience pipeline. So I'd say, oxybate, number one; further diversification of revenue through our launches, number two; and number three, that ability to use our capital to continue to broaden the growth sources for our investors going forward.

Okay, got it. Maybe we can spend a little more time on GW. I was hoping you could talk a little bit about the rationale for the transaction. I know you've highlighted the cultural fit a number of times, but what is it about their platform?

Yes. Well, Jazz set out a couple of years ago really to think about, what would a transformative deal do for the company? And what would make a good counterparty for a transformational deal? And we pretty quickly settled on a major revenue driver, so an already significant product with good growth prospects in front of it would be a key component of an attractive transaction; second, something that would really broaden our pipeline; and third, something that would really provide an excellent return to our investors. And with the GW Pharma deal, we're getting that franchise with Epidiolex of a product already north of $500 million and soon to be a blockbuster, we believe. We're also getting that pipeline. And from a financial perspective, we can lever up to do the transaction and then quickly delever, given our cash flow back down to less than 3.5x into 2022 while accelerating our top line growth, diversifying our revenues with nearly 65% of 2022 pro forma revenues expected to come from relatively newly launched products, and then have accretion at the bottom line in the first full calendar year together, 2022 with strong accretion thereafter. So it really checked all our boxes. And as we prioritized available opportunities where we saw a good fit, GW Pharmaceuticals was first on our list. And as people can now see from the background of the transaction section in their proxy, we reached out mid last year to start those conversations because we believe this was the best match for Jazz.

Where do you think your view of the commercial potential for Epidiolex may differ from The Street, if at all and why? And how do you see the growth for that product, both in the U.S. and ex U.S.?

Yes, Jess, so I'll take that one. I mean, Epidiolex, I think many do see it as a very strong brand with a significant upside, major new treatment option for epilepsy. We've been very impressed with GW's performance and only the second year on market in the U.S. On a global basis, they did $510 million. And there's still significant room for penetration in the indications that they're approved for. They've referenced 40% penetration Dravet, 30% in LGS, 10% in TSC, which was the newest indication where also the dose could bump up. So we see plenty of room for growth. What we found from market research as we did the diligence is that the caregivers, the patients and the physicians were all very eager for a new treatment option with the cannabinoid backbone that could combine well with other therapies. And so the durability of therapy that we see when patients go on is quite strong. Europe is just getting going, so sort of minimal sales were reported last year, but with significantly more expected this year. They've secured favorable reimbursement in many of the countries. And so we're looking forward to working closely with the GW team to realize the full potential. And that will include additional indications and data generation.

What strategies are you pursuing to maximize the potential returns of this deal to shareholders?

Well, one clear focus is, of course, Epidiolex. So we're looking forward to leveraging all of the momentum that they have, the teams that they have in place and supported with sort of Jazz efforts, near term, just global rollout and execution, but longer term, data generation, new indications and even new formulations. And then, clearly, there's the pipeline of programs, including nabiximols potentially for the U.S. in the not-too-distant future and then leveraging the fuller platform for other neuro assets as we were expanding our own neuro business.

Can you walk us through the IT picture for Epidiolex and any plans or any steps you plan to take to further strengthen and extend it?

Yes. Jess, I'll point out that there's strong IP in place for GW Pharmaceuticals. They've got 85 patents, more in prosecution, including 13 Orange Book-listed patents with exclusivity out to 2035. I'll also point out, this is a really unique manufacturing process. This is not, in general, how drugs are produced. And I think there's some know-how expertise and facilities that are specific to the production of Epidiolex, which also provides some protection against genericization. We'll, of course, continue to work on pursuing additional IP as GW would have also, by the way, in the years to come. But we think it starts with a really strong position and we're confident of long durability of this asset.

And beyond Epidiolex, what's the progress with other pipeline assets like nabiximols? And how should we think about the size of the market opportunity there?

Rob, you're on mute.

Yes. Jess, as you know, nabiximols are approved as stat effects in several European countries. The next opportunity in the U.S. would be around specificity in the context of multiple sclerosis, which is a really, really big unmet medical need. From there, there's potentially a launching point into other types of specificity. And our GW colleagues have been in close discussion and planning with the FDA on those potential indications.

Great. Maybe we can switch gears to the, I guess, the legacy neuroscience business. I was hoping you could share some insights from the initial launch of Xywav so far.

I like that you're calling it our legacy neuroscience business, including products that were just launched in November. We couldn't be more pleased with how the Xywav launch has rolled out. As a reminder to everyone, Xywav takes the active ingredient in Xyrem oxybate and delivers it with 92% less salt. So up to 1 gram, 1.5 grams or more less salt every night in a chronic condition where patients are known to have high cardiovascular risk. Narcolepsy patients, in general, have high cardiovascular comorbidity. So that engineering out of the salt really provides a healthier lifelong treatment option for these patients. And that message is really resonating with patients and with physicians early in the launch. As we said, by the end of our second full month on the market, we had 1,900 patients on Xywav at the end of December. That compares to a total of 15,300 average oxybate patients, meaning Xyrem plus Xywav over the course of the fourth quarter. So that's really rapid conversion. And we're seeing it from all patient types. There really isn't a patient for whom Xyrem is a better treatment option than Xywav. So really excited to be out educating people about the importance of this modifiable risk factor. Cardiologists could tell all of us to change our diet or make other lifestyle changes. That doesn't mean patients always comply. Here's something a doctor can do by changing a prescription that they know will benefit their patient in reducing cardiovascular risk.

Great. And what's the progress with payers? Where are you in terms of securing broad coverage?

Yes. So Jess, we're very much on track with what we intended at the beginning of the launch is to have depth, quality and coverage on the commercial side, similar to what we have with Xyrem, which is 90% access on the commercial lives. Within 6 to 9 months, we want quality coverage, not necessarily at 90%, but we're making very good progress there. We've had ongoing dialogue with the payers, both the major ones and less major. As of last earnings call, we had referenced 2 of 3 of the major PBMs, and now we're working on the third and other payers, and we'll be updating on a quarterly basis. But we're pleased with access to care. And we also ensured at the time of launch that we would have a full suite of services to support any patient conversions or new patient adoptions over to Xywav so that did not be a limitation. And that seems to have worked very well and got us fast out of the gate.

Great. sort of touched on this, Bruce, but is there any other color you can add to the patient mix that you're seeing with Xywav and reasons driving adoption?

Yes. Just to add on to what Bruce said, we really believe any patient who could benefit from oxybate therapy that Xywav should be the treatment of choice. We saw from the clinical studies that you could convert over patients from Xyrem to Xywav dose for dose, no washout, very easy to titrate over. And it turned out that it's the same in the real world. We're getting that same experience in the clinic. You can also take naive patients and dose titrate them up as you would with a typical oxybate patient on Xyrem. So really, all patients who are currently on Xyrem, all patients who had tried Xyrem and that dropped off, new patients and then patients who were previously contraindicated because of sodium concerns. So we're seeing potential growth in all those segments. Near term, there is a focus on where Xyrem patients are being treated today longer term or not even longer term but getting ready for later this year. We're also looking forward to launching this product into idiopathic hypersomnia, which is a significant new area and where there is no FDA-approved treatment.

Great. Maybe just one more on this topic before I switch to some of the questions coming into the portal. And thanks, again, for using the ask-a-question feature. Over the long term, how should investors think about the evolution of the oxybate franchise?

Well, Dan has just given you some of our excitement about the Xywav launch, which is off to a great start. But as we said, there's the opportunity there to add patients who might not have been good candidates for Xyrem due to salt concerns and then to move into the idiopathic hypersomnia market, which is estimated to be sort of 50% to 100%. Again, the size of the narcolepsy market. So a real growth opportunity after years of relatively limited but successful volume growth each year. We now have the opportunity to really benefit patients who have no FDA-approved therapy today. Once we move out to January 1, 2023, or earlier under certain circumstances, if there's a significant market decline in Xyrem dollar sales, we'll have authorized generic entry by Hikma. And that's through our REMS under an agreement with us with substantial economics to Jazz. But the important thing to remember is if patients are well controlled on Xywav, you have to ask whether moving back to a product with more than 10x the sodium contained in Xywav at a level that puts you above the daily recommended maximum sodium intake according to the American Heart Association makes sense in this patient population that's taking a drug chronically and is known to be a high cardiovascular risk. So if there are patients who are still on Xyrem, I can see them moving over to an authorized generic in which we have substantial economics. But in the meantime, we'll be growing Xywav, including into a new market, remembering that we did our pivotal Phase III trial for idiopathic hypersomnia with Xywav. So IH would be in the Xywav label, not the Xyrem or authorized generic labels.

Okay, great. Maybe switching to some of the incoming questions here. First one is going back to GW, and forgive me if I mispronounce this product, but can you talk about why peak sales for nabiximols in the U.S. would be any different from peak sales for Sativex ex U.S.?

Yes. Dan, do you want to take that?

Yes. I think one way to think about it is, obviously, there's going to be additional clinical data and an FDA-directed PI that we don't have at this point. That's important. Two, I think the overall acceptance at this point, which is important for the start of the launch for cannabinoid-based medicines is in a -- they're very different places than Sativex was ex U.S. And then, of course, sort of the number of patients and the price point all speak to significant opportunity. One thing we've heard, for example, MS, which could be spasticity, it could be the first indication, hopefully, of many. There's already a number of patients who are seeking cannabinoid-based treatments from the dispensary and sort of non-FDA-approved therapies. And there's a very similar dynamic in epilepsy where patients and caregivers were looking for cannabis-type medicines but without the FDA sanction, without the GMP quality and without the label. And once a product like that is available, there's a very significant shift in the market and we could expect a similar dynamic with spasticity.

Great. Next one coming in. Can you expand on why you see orexin agonist as complementary to Xyrem and Xywav? What are you seeing in the field as WAKIX now has the cataplexy label? Is it competing with Sunosi or Xyrem? And any update on the Avadel Paragraph IV Certification? Will Jazz need to sue FDA to figure out the status before October?

Okay. Lots of questions in there. Let me start with Paragraph IV Certification. Jazz has made its point of view clear that we believe Avadel should have to certify to our Orange Book-listed patents around safe use of Xyrem related to the distribution system and related to drug-drug interactions. We've also said that, that certification could come at any point during the NDA review process. So no more to say on that right now. In terms of WAKIX, I would say they are publicly reporting their results and you can see how they're doing. What we're commenting on is we have not seen an impact on the -- our Xyrem or Xywav business. Oxybate has long been sort of the gold standard of care in narcolepsy. It's a nighttime medication taken, which has an impact on sleep at night. And even though there's a short half-life of the drug and it's gone from the body when you wake up in the morning, it provides daytime benefits and reduction of key symptomatology in excessive daytime sleepiness and cataplexy. Now we know that a lot of patients take oxybate at night and then take a daytime agent, take a wake-promoting agent or a stimulant. Probably 80% of our oxybate patients are also taking a daytime agent. Of course, we've launched one of those agents. You mentioned Sunosi, which we're happy to see growing as it moves into its next phase of launch with broadened reach and frequency into the OSA market with a new TV DTC ad campaign. But again, we just haven't seen an impact of WAKIX on our business. And maybe, Rob, I'll ask you to comment on the orexin question.

Sure. So maybe picking up or highlighting something you already stated, Bruce, which is near narcolepsy, we see as a 24-hour disease, where a significant root cause is the disrupted nighttime sleep. That's one of the reasons why oxybate has been such an important therapy especially for severe patients. Getting that consolidation and improvement in nighttime sleep has significant benefits during the day. And with Xyrem or Xywav, we see that across all patients, even the most severe patients. The orexins are an area of significant interest. Certainly, that pathway is very relevant to narcolepsy. So far, we've only seen limited data though with the drug that was used really as a probe compound given as an IV infusion. And so those data are somewhat limited to know whether they would have the same kind of impact, say, on cataplexy as they seem to be on excessive daytime sleepiness. And so that's why we think of oxybate continuing to be a backbone of therapy for patients with narcolepsy, even if additional therapies were added during the day as an additional learning agent.

Another one here. At what point can one assume Xywav is not getting orphan drug exclusivity? And would getting orphan drug exclusivity for Xywav block either Xyrem generics and/or Avadel?

So there is no PDUFA clock. There is no goal date for an orphan drug exclusivity decision. We're awaiting one. We obviously believe Xywav should get it. What would that do with respect to other products? It would not have any impact on the Xyrem generics so no impact there. In terms of other oxybate products seeking approval for the treatment of narcolepsy, they'd have to show some benefit over Xywav in order to get that.

Next one here. I'm not sure if you'll -- well, can you quantify the dollar amount you would owe CMS for each Xyrem script under the new rebate cap rules? And will the same rebate arithmetic apply to Xywav, given it's a follow-on?

So I think the answer is no to the latter question. Xywav is a newly approved molecule. And on the other question, that doesn't take effect for a number of years, and I'm not sure we'll actually be selling Xyrem at that point in terms of -- at that point, there are authorized generics of Xyrem available. Our efforts are behind Xywav.

Okay. Great.

I should also just point out for completeness. Government pay is not a significant portion of our oxybate revenue stream. This just tends to be a younger disease with 70%, 80% of patients' commercial pay.

Can you -- switching to the oncology business here. Is that business -- is the oncology business currently profitable? How core is it to your long-term business? And with broader diversification, could it make sense to reassess its importance within the company?

So we're really excited about our oncology business, Jess. We had our first year north of $500 million of revenues in 2020 and we've guided for 2021 closer to $800 million. So this is a rapidly growing business. We're excited about our new brands, whether that's Zepzelca just launched mid last year, which I'm sure we'll talk about. But again, that launch is off to a great start with lots of growth potential in second-line small cell lung cancer as well as beyond in other areas we're investigating it. And then we're coming up on what we believe will be a really successful launch of JZP-458 into the acute lymphoblastic leukemia market, providing a reliable source of this important drug not only for pediatric patients but as we expand into adolescent and young adult market. And as we expand into further geographies where we've been limited historically by capacity problems with the earlier Erwinia asparaginase products. So we're really excited about the growth of this business, and we're excited about the pipeline we have behind our commercial products. So as we said when we announced the GW transaction, we'll have 3 large, growing and durable franchises in our sleep disorders, in oncology and then in epilepsies to build off of with a strong pipeline behind it. So will we consider different configurations of the business in the future? Maybe. But for right now, we've got these growth opportunities right in front of us. In terms of profitability, we are investing across our business right now in 5 product launches. So our margins aren't quite what they'd be if all those products were out of launch mode and already large, but this is a profit source for Jazz.

Okay. Coming back to a few more on the sleep neuro business before we move to more on oncology, I know you've talked about the maybe like non-unanimous receptivity to a once-nightly product. But I think you've also said you're working on a once-nightly low-sodium oxybate. When can we expect any further updates on that?

Jess, we are continuing to work on our low-sodium once-nightly program. I don't have any time line updates for you at the moment other than to say that we are continuing to work there. I would emphasize, though, that we've prioritized the low-sodium program with Xywav, given the really critical importance of that to narcolepsy patients, and Bruce and Dan both spoke to that earlier. We also know from our own discussions with patients and research that many patients really prefer the flexibility of twice-nightly. If you take a once-nightly formulation, really commit you to being out for the whole night. For many patients, the flexibility of twice-nightly is really preferred over a once-nightly option. And remember, given the nature of this drug, patients will have to choose between one or the other. It's not as if you could have both on your nightstand. And so that flexibility definitely comes through in the research we're doing. And I would just remind you that the label already for Xywav not only allows for a split dose but flexibility around uneven doses, which is really critical for patients as well.

And Jess, just as a reminder, we've put out our expectation that if we go out into the future when there are multiple oxybate products on the market, including potentially authorized generics, including potentially once-nightly, we still believe Xywav will be the dominant product. In other words, we believe Xywav will have over 50% of all oxybate patients in the year 2023. That is different from -- I'm not giving guidance about how the Xyrem business may result in adoption of Xywav. I'm just saying if we go out into the future when there are multiple products available, we believe Xywav is the best of those products.

Okay. Maybe switching to Sunosi. How do you envision the next phase of growth for that product? And can you walk us through -- it seems like there's been sort of an evolution in the efforts that you've undertaken to support further adoption as it relates to the sales force. Can you walk us through kind of what that evolution has been and why?

Yes. So just on Sunosi, we launched this back in 2019 with a near-term focus in narcolepsy where we had a strong beachhead, and we got very rapid uptake, good market feedback. The second aspect with a more broad retail drug is to ensure good payer coverage. And by March of last year, we're approaching 90% of payer coverage, which is outstanding for a brand at that stage of its life cycle. As we were expanding into OSA, where there is some conversion of patients who are on modafinil and other wake-promoting agents, and we believe we had some elements that really differentiated the product with very strong efficacy parameters as well as 9-hour duration of benefit, we were struck by COVID. So as we were trying to drive into OSA to both increase the rate of diagnosis of excessive daytime sleepiness and the conversion of the market to Sunosi, we ran into that issue. That started to resolve itself towards the end of last year. And so that's when we, or at least in the sense of more non-COVID patients were getting back into the offices, including OSA patients. And so we expanded with a 50% sales force through a contract sales organization in November to really reach a broader group of targeted physicians who were already prescribing wake-promoting agents for their OSA patients. So somewhat low-hanging fruit in terms of targets we hadn't been to. Come January, we've been activating the patient, the consumer to come into the office and have that dialogue with their physician by expanding into TV advertising. And then in March, to benefit both the narcolepsy investments, the idiopathic hypersomnia launch coming up and continued support for Sunosi, we've reorganized our internal sales force and expanded it to have 2 sales forces instead of one, one focused in the narcolepsy IH market, which is a strong overlap in terms of physician base; and the second, to expand our reach and frequency complemented by the CSO into OSA. So this is a critical year for growth to see the return of those investments. And I think, particularly, the second half will be a very telling sign if those investments pay off. The product profile, we know works well. Physicians who are using the product with, overwhelmingly, I think, 98% of the time, recommended to peers to use it in their patients. So it's really just boots on the ground and activation of the consumer with DTC.

Great. What about your pipeline assets, 385 and 150, can you briefly touch upon the potential market opportunities and plans for the next stage of development?

Yes. So maybe I could start with the development and invite Dan or Bruce to add to that as well. So both programs are going to initiate new Phase II trials this year. 385 will be a IIb trial and potentially contributing to a pivotal data set. That's in the context of essential tremor, which, as you know, is a huge unmet medical need. We have estimated that in the U.S. and in EU are the total of 11 million patients and prevalent. It's been 50 years since there's been a new drug. We know that the approved drugs are not particularly effective. And so we're pretty excited about bringing that program forward. And then likewise, for JZP-150, which is our FAAH Inhibitor for PTSD, also a significant area of unmet medical need. In the U.S. alone, we think more than 2 million patients suffering from PTSD. Again, with decades without a new approval. The only approvals in PTSD have been SSRIs, which were not particularly effective. And so we're excited to move both of those to the Phase II level this year.

Great. So switching to oncology. You're just starting out with the oncology guidance. From a high level, when we think about the revenue guide for the oncology franchise, I know you don't break it out by product, but which product is likely going to be the main driver of that growth?

So there are really 2, Jess, that I think are the main drivers of that growth. The first is Zepzelca. Remember, Zepzelca got off to a great start in 2020. We got an accelerated approval and launched an immediate addition to the NCCN treatment guidelines for second-line small cell lung cancer, and we did $90 million in revenues in less than 6 months on the market and exited the fourth quarter with an annualized run rate north of $200 million. And there's a product that we had on the market for half a year in 2020. We'll have it on the market for a full year in 2021 and with growth as we continue to penetrate in second-line small cell lung cancer, where we believe this product relative to the prior standard of care, topotecan, has a number of advantages in terms of response rate, response duration, toxicity, ease of administration. And then we're excited about where we can go beyond 2021 as we continue to investigate broader use of Zepzelca, including in first-line in combination with IO. The other excitement in our oncology business is really bringing JZP-458 to market. We're attempting to go from essentially IND to on market in 2.5 years, which is just extraordinary performance by our R&D team to meet this unmet need, right? The market needs a reliable, in this case, recombinant Erwinia asparaginase to make sure that all patients who develop an allergy to the E. coli-based asparaginase can continue getting their full course of asparaginase treatment because we know that gives them the best cure rate. So really excited to bring that product to market in the U.S. and as quickly as we can to expand to other markets around the globe.

So what is -- what remains kind of the potential approval and launch of 458?

I could give just a quick summary of where we are. As we mentioned already or disclosed already, the submission was initiated at the end of last year. Jess, it's under a real-time oncology review program, which allows us to submit data as it becomes available and is ready for submission, even while we're preparing some of the other modules and components of a BLA. And so that process is ongoing. It's iterative with the FDA. Where there are questions, they can ask them, even before seeing final modules based on the data they're seeing, and we're having dialogues around how to update that file as we move along. And so really, the next is to complete the submission. And we'll be -- based on all of that, we continue to reiterate that we're ready for a midyear launch.

And Jess, I'll just add, our excitement here is that we had a prior product that peaked at just north of $200 million in sales, but was always severely supply constrained. So our ability to get full use in pediatric adolescent, young adult markets just wasn't there. So to really put us in a position where we can go out and help ensure all patients who would benefit from this asparaginase treatment get it is an exciting one.

And then of course, we're in dialogue with other health authorities around the world, in particular, Europe and Japan around how to quickly leverage the data we're already generating in the ongoing trial, potentially, to support approvals around the world.

Maybe while we're on that topic, Rob, how should we think about the time lines for ex U.S. launches for 458?

Yes. I don't know that we've disclosed any time lines, but I would say that the considerations around the globe should be similar in terms of the data that are needed to approve a product like this. And so we do think that the ongoing trial, which initially focused on intramuscular injection and then shifting over to intravenous injection all under that same protocol, we hope will be able to significantly leverage for approvals around the globe. And as we have that dialogue and share those data in Europe, say, and in Japan, we'll have more clarity on what else might be required and that will ultimately dictate the time lines. In Japan, for example, as you know, often, there's a focus on ensuring that there's no ethnic differences in exposure and pharmacodynamic activity. Those considerations here are not really significant, given that it's a biological agent and it's also dosed based on body surface area. And so we think that, at least we hope as we progress discussions with PMDA, that there'll be sort of bridging studies rather than having to repeat a lot of the work that we've done.

I guess thinking about the midyear approval and launch, how should we think about the potential ramp of 458 in that transition from Erwinaze? And also, you kind of said -- suggested that this could have potential to be a larger product than Erwinaze, but there's always supply constraint. So what do you think the size of the market opportunity is for 458? And what are you doing to ensure a better update?

Yes. Jess, we haven't given a complete number there. In part, we've been, as Bruce said, supply constrained. We also pulled back all promotion and medical efforts on the brand for several years because we're just sort of triaging product supply on a patient-by-patient basis. So to get back to a market, a $200-plus million and start to do some of what was happening at that point that was growing the market, looking -- immediately intervening when patients had a reaction and also looking for silent and activation to the E. coli-based therapy because, again, the overall treatment goal is to stay on this Erwinia or asparaginase therapy and get to the very high cure rates. We're supported in this effort by working closely with COG. So the Children's Oncology Group really treats the vast majority of pediatric ALLs. So right out the gate, we'll be working closely with them to integrate in 458 into the treatment protocols at the local institution as well as at the society institution. So we're excited to see where this can go and then to penetrate into adolescent young adults into new geographies, and we'll be giving further updates as that product ramps up. Right now, it's all-hands-on-deck to get the BLA completed, the review completed and to target this midyear launch.

Great. Maybe switching to Zepzelca. What are the next steps towards a confirmatory trial? And how should we think about the development strategy in small cell lung cancer and kind of ultimate commercial potential for the product?

Sure. So starting with the confirmatory trial, as we disclosed previously, we had only an initial interaction with the FDA to share the ATLANTIS data, and we agreed that we would come forward with a new plan for a confirmatory trial. We've been working with our pharma partners on that and expect to be meeting with the FDA soon to discuss that further. In terms of additional development, there are a number of things we're doing. The place that I would focus first in the small cell area is in first-line. We -- as we mentioned previously, are planning to move Zepzelca into the first-line setting as an add-on therapy for patients who have extensive stage small cell lung cancer. We think there's a very big unmet medical need there where patients have -- even after the addition of PD-L1 antagonists, have a median expected survival of only about 12 to 13 months. Progressions occur very rapidly after the end of the initial chemotherapy, which is limited to just 4 cycles or 3 months. And so by the addition of an agent like Zepzelca, which can be continued even beyond the initial chemotherapy with platinum and etoposide, we hope to extend that progression-free survival and ultimately, overall survival as well, reaching more patients because not every patient gets to second-line and increasing the duration of therapy for Zepzelca that'll hopefully also increases the quality of life for patients if you can really preempt their progressions.

Great. It looks like we've got one minute left. So the wrap-up question for all of these sessions is -- and you can go around across the group. What's your favorite Napa wine?

Peter Michael.

I like Joseph Phelps.

Silver Oak. Is that Napa or is it -- I'm in the East Coast...

You're a silly guy. What's yours, Jess.

Maybe Myriad.

Also, I'll put in a plug for Arietta because I like the musical theme and like the winemakers.

Great. Well, thanks so much, everyone, for tuning in and thanks so much to the Jazz team.

Thanks, Jess.

Likewise. Bye.