Great. Good afternoon, everyone. My name's Jess Fye. I'm the Large-Cap Biotech Analyst at JPMorgan, and we are delighted to be continuing the conference in person today with Jazz Pharmaceuticals. This year's a little different than past years. We're not going to switch rooms for Q&A. After the presentation, you can raise your hand, someone will bring you a mic, or you can use the portal. Send me a question on the iPad up here, and I'll ask your question. But with that out of the way, let me turn it over to Jazz Pharmaceuticals' Chairman and CEO, Bruce Cozadd.
All right, so thanks, Jess, and thanks for joining us today. Today starts my 32nd consecutive JPMorgan conference. Hard to believe. I did start young, just for the record. You know, it's my pleasure to be able to present an update on Jazz Pharmaceuticals' progress today. During 2022, thanks to the passion and the innovation of our 3,000 talented employees around the globe, we improved the lives of more patients. We had strong top-line growth. With record product sales and disciplined investments, we advanced our pipeline, and we positioned the company well for Vision 2025. Okay, now the exciting part. I will be making forward-looking statements today. They're subject to risks and uncertainties. Please see our SEC filings, including this morning's 8-K, for more information. Next note, I will refer to some non-GAAP financial measures for a full reconciliation to GAAP. See the slide deck posted on our website.
I'll also refer to guidance, and unless I explicitly say otherwise, that's as of the time we delivered that guidance on November 9th. One last programming note: some of you will notice I have a tremor in my right hand. That's not nerves. If my left hand starts shaking, that's nerves. So that's how you tell them apart. Okay. At Jazz Pharmaceuticals , our purpose is to innovate to transform the lives of patients and their families. With a strong presence in neuroscience and oncology, we focus on diseases where we think we can truly make a difference for patients like Casey and Leighton, pictured here. In 2023, Jazz Pharmaceuticals is going to celebrate its 20th anniversary. And over those 20 years, we've remained focused on our purpose and delivered consistent results.
I'm happy to say today we will achieve our total revenue guidance for 2022, as well as our revenue guidance for each of neuroscience and oncology. You can see here that through our commercial expertise, we've got a track record now of 18 consecutive years of revenue growth, with revenue growth over the past five years at 18%. More broadly, I'd say our executional excellence across commercial, R&D, and corporate development gives us a lot of confidence about the future. Last year, at this conference, we rolled out Vision 2025 to deliver sustainable growth and enhanced value as we continue our transformation to a high-growth global biopharma leader. There are three key pillars to Vision 2025, and I'm happy to provide an update on all of them today across commercial, pipeline, and operational excellence. Of course, Vision 2025 is built on our core strengths, starting with commercial.
We've got a great track record of successful launches, including launches of Xywav, Zepzelca, and Rylaze over just the past three years. And on the pipeline side, we've continued to add new capabilities, increase our productivity, all accelerated by the acquisition of GW in 2021. And on the operational excellence side, we've got a great track record of disciplined capital allocation as we invest across our current business and corporate development opportunities. 2022 was a great year at advancing our position toward achieving Vision 2025. Starting on the commercial side, as I mentioned, we had strong top-line growth, really led by the continued success of those three product launches: Xywav, Zepzelca, and Rylaze, but also, importantly, benefiting from continued strong growth of EPIDIOLEX.
On the pipeline side, in addition to advancing our clinical portfolio, we added three exciting new molecules to our pipeline, including most recently Zanidatamab, where just last month our partner Zymeworks presented positive top-line data in their lead indication. During the year, we also submitted four new INDs and started seven new clinical trials. On the operational excellence side, we have really strong cash flow: $930 million in operating cash flow over the first three quarters of 2022, and an operating margin at the midpoint of our previous guidance that would put us at about 49%, substantially up from the 43% we recorded in 2021. And we've delevered two full turns since the close of the GW acquisition in May of 2021, so in a period of about a year and a half, two full turns.
All of this means we have the financial strength to continue to invest in sustainable growth and enhanced value creation. Corporate development remains core to us achieving our strategy to create value for patients and shareholders and to achieve Vision 2025. We look for opportunities that'll build on our insights, our capabilities, our infrastructure, where we can efficiently launch products with long durability. On this slide, we list just a couple of the strategy-aligned transactions we've completed recently that add to our product diversification, solidify our leadership in sleep, and build on our oncology expertise. Starting with GW in 2021, this not only brought us EPIDIOLEX, which we believe has blockbuster potential. It also expanded our neuroscience pipeline, gave us a cannabinoid research platform, and expanded our global operational footprint. The orexin-2 agonist program brought us a clinical stage, exciting new mechanism of action in sleep.
Zanidatamab brought us a novel late-stage asset with compelling anti-tumor activity. And Zepzelca has proven to be a rapidly accretive deal with over $500 million in revenues since our launch in mid-2020. We think our capabilities across commercial and R&D, along with our structural flexibility, position us as a partner of choice. And we do believe this is a very favorable environment for companies looking to add new and innovative assets. On this slide, I want to talk about how rapidly our revenue base has been transformed over the past few years, starting on the left with 2019. Since 2019, the addition of EPIDIOLEX through acquisition, the launches of Zepzelca and Rylaze, and the very successful commercialization of Xywav to date have led to a transformation in the diversification of our revenues.
I've already mentioned that we'll meet our top-line guidance of $3.6 billion-$3.7 billion in total revenues. I'm also happy to say we'll meet our previously stated target of 60%-65% of the net sales in 2022 coming from newly acquired or launched products since 2019. But we're not done yet. We'll continue to bring new products out of our R&D portfolio. We'll continue to bring in new products through corporate development. We'll continue growing Xywav, and we'll continue growing EPIDIOLEX and our oncology portfolio. And to achieve Vision 2025, we'll have an even more diversified revenue stream, as you can see on the right-hand side. Okay, let's take a little deeper dive into the commercial side of our business. We said we thought we could achieve $5 billion in revenue in 2025. And let's walk through the composition of that.
Starting with oxybate, we believe oxybate is a very durable franchise led by Xywav, and we predict $2 billion in revenue continuing from oxybate in that year. EPIDIOLEX continues to grow. We believe it has important call. EPIDIOLEX has blockbuster potential and will do over a billion dollars in revenue in 2025. Same thing with our oncology portfolio. I just said we reiterated our guidance for oncology at $860 million-$920 million in revenue in 2022, with growth led by Zepzelca and Rylaze. We think we'll clearly be over a billion dollars in 2025, and that EPIDIOLEX and oncology together would represent about $2.5 billion in sales, with the remaining $500 million in 2025 revenues coming from products emerging from our pipeline or corporate development opportunities. oxybate.
You know, we've been at this for 15 years now, establishing oxybate as the treatment of choice in narcolepsy with a robust FDA-approved REMS and distribution system and a really great trusting relationship with sleep HCPs and patients. But during that time, we were busy too getting ready to improve the state of narcolepsy treatment. And a key milestone there was the approval and launch in 2020 of Xywav. Xywav is better than Xyrem. It's reduced sodium load by 92%. And the FDA said when granting orphan drug exclusivity that Xywav was clinically superior to Xyrem because of greater safety due to the reduced sodium load and an expectation of fewer cardiovascular events. We followed up our approval of Xywav in narcolepsy one year later with an approval in idiopathic hypersomnia.
And I'm happy to say we've got over 9,500 patients on therapy with Xywav today, now exceeding the number of patients on Xyrem, both in total and even just within narcolepsy. On January 1st or 2nd, we did see an AG launch of Xyrem. But as a reminder, we do get meaningful royalties on Xyrem AGs. The expansion into idiopathic hypersomnia creates a great growth opportunity for us. IH is a serious and disruptive sleep disorder with high unmet need, and we are the only approved product in this space. With 1,450 patients on therapy after just our first few quarters on market, we believe we're making excellent progress, calling on an audience we already know with 90% overlap to our existing audience, with great reimbursement at 90%.
And our message is really resonating as we engage in the first launch in this space in market education, helping HCPs diagnose IH and identify appropriate patients. Some believe this opportunity could equal the size of the narcolepsy opportunity. I'm not saying that's going to happen next year, but as we've proven over time, we've really grown that narcolepsy opportunity, and we see similar opportunity with IH. So if we put narcolepsy and IH together, you can see our track record of success since our launch. And Xywav is firmly on track to be the oxybate of choice in 2023 and a key part of our ongoing commercial portfolio through Vision 2025. I'm happy to say that of new patient starts today, the vast majority of patients new to oxybate are getting Xywav rather than Xyrem.
Let's turn now to EPIDIOLEX, the first and only FDA-approved prescription cannabidiol and a treatment associated with seizures, a treatment for seizures associated with tuberous sclerosis complex, Lennox-Gastaut syndrome, and Dravet syndrome with broad-spectrum efficacy. We see significant opportunity for continued growth of EPIDIOLEX, mostly in LGS and TSC, as well as in treatment-resistant epilepsy and outside the United States. In the U.S., our message about the synergistic effect of EPIDIOLEX when added to clobazam is really resonating with prescribers who often use a polypharmacy approach for these treatment-related epilepsies, with clobazam being a very widely used agent. They also like the clinical and safety profile, the combinability of this agent, and its unique mechanism of action. We're committed to creating additional data through real-world evidence and clinical studies in new seizure types and to broaden the understanding of the use of EPIDIOLEX.
We were very pleased to see 19% growth in EPIDIOLEX if we compare the 12 months ended September 30th with the prior year period. Market research tells us that 60% of providers are moving EPIDIOLEX up in their treatment algorithm. We continue to add new prescribers. Our volume of engagement with HCPs is growing, and we're continuing to expand ex-U.S. Pricing and reimbursement in France was completed in December. That makes the 1/5 of the five major European markets to launch. And we have additional launches upcoming in smaller European markets, and we continue to pursue even broader geographic expansion, including with our phase III trial ongoing in Japan. Here you can see how our oncology business, a diversified business, has continued to grow, most recently accelerated by our U.S. launches of Zepzelca and Rylaze. And you can see why we're excited about the ongoing growth of this portfolio.
Zepzelca has been rapidly established as the treatment of choice in second-line small cell lung cancer, achieving over $535 million in revenue since launch in mid-2020. And as I said, proven rapidly accretive. We believe there's continued growth opportunity in second-line small cell lung cancer, and we're generating additional data to support that. We're also very excited about the potential of moving into first-line treatment in combination with immuno-oncology. You know already we have an ongoing trial with Roche, a phase III trial in first-line small cell lung cancer in combination with Tecentriq. And we're happy to say that trial should complete enrollment in 2023. The Rylaze launch has been a real success story with $286 million in revenue since launch mid-2021.
Now that we've solved the supply constraint for our non-E. coli-derived asparaginase that's used to treat patients with ALL and LBL who develop hypersensitivity to E. coli-derived asparaginase, HCPs say they're returning to best clinical practice and switching therapy at the first signs of hypersensitivity. Our penetration in that pediatric market is great. We're also seeing increased use in the adolescent and young adult market. Couple that with the recent November approval by FDA of our Monday, Wednesday, Friday intramuscular dosing regimen, the pending RTOR review of our IV administration, the pending European filing which we submitted in mid-2022, and our efforts in Japan, we see lots of growth opportunity for Rylaze moving forward. Okay, that's the first pillar, commercial. Let's move to the second pillar, pipeline.
You know, I think Jazz Pharmaceuticals has long been known for commercial execution, but I think we should equally now be known for our R&D execution with a tremendously productive R&D effort with five product launches across 2020 and 2021, substantial clinical advancement, and new broadening of our pipeline. In 2022 alone, as I mentioned, we added three new molecules. We expanded our Suvecaltamide or JZP385 program to Parkinson's disease, tremor, as well as essential tremor. I mentioned the four INDs and the seven clinical trial starts, the positives, Zanidatamab, Zepzelca top-line data, and the approval of Rylaze. All of that execution and track record makes us confident of our Vision 2025 to deliver at least five additional novel product approvals by the end of the decade.
You can expect with our increased investment and catalysts in our R&D pipeline, you'll be hearing more from us about our progress and the opportunity in our pipeline, both this year and in 2024. You know, beyond the breadth and depth of our pipeline with 23 novel candidates advancing, including six significant development collaborations, I'm really proud of our expanded capabilities, including enhanced medicinal chemistry and translational biology capabilities, and really differentiated capabilities across cannabinoids and nanoparticle drug delivery. We've got significant capabilities measured by our facilities with four major lab and production facilities across Europe and Canada, over 700 R&D employees with over half of our senior R&D staff possessing PhDs, PharmDs, or MDs. All of this R&D effort is built on top of our history of disciplined capital allocation across our existing pipeline, as well as new corporate development opportunities.
Let's take a look at just the near-term R&D pipeline opportunities and value inflection points across what I think is a robust neuroscience and oncology mid- and late-stage portfolio. In 2022, we expect catalysts to include JZP150 readout and PTSD phase II top-line data. In JZP441, our orexin-2 receptor agonist program, we do expect human proof of concept and healthy volunteers this year. I've already mentioned that with Zepzelca, we expect full enrollment of that phase I combination trial in collaboration with Roche. And with Zanidatamab, expect continued progress. This month at ASCO's GI Symposium, we expect to see additional phase II data from the continuing first-line trial in GEA. And I'm happy to say we've been added to the I-SPY breast cancer program effective this year. In addition to the late-stage activities, we'll continue to submit new INDs, of course.
Okay, which brings us to the third pillar of Vision 2025, operational excellence. Our strategic capital allocation has been aimed at those things we think are highest priority. And with our strong cash flow, our strengthened balance sheet, and our improving margins, we have the flexibility to make significant investments across commercial, across pipeline, and across corporate development to drive sustainable growth and enhanced value. With our track record of delivering top and bottom-line growth, with that focus on operational excellence, with the investments we're making across commercial, across R&D, and across corporate development, we think we're very well positioned to achieve Vision 2025. In December, we published our first ESG report.
I believe with our focus on our core values, strong corporate governance, environmental stewardship, and social responsibility, we're in great position to execute on our strategy and our vision of long-term value creation for patients, for employees, for shareholders, and other stakeholders. We're excited to continue to update you on our ESG process as we focus on building a healthier world. In conclusion, let me say I have great confidence about Jazz Pharmaceuticals' future based on our strategy, based on our 2022 execution, based on that strong financial position with additional flexibility to invest and transact to grow our business, based on our pipeline with near, mid, and long-term catalysts, and those expanded capabilities on both the commercial and the R&D side that I think make us a corporate development partner of choice.
In short, I think we've got the right strategy, the right financial strength, and the right team to achieve our objectives. So let me conclude by thanking our employees for their ongoing efforts to improve the lives of patients and make Jazz a great place to work, and also thank our partners and our shareholders for your ongoing support. And with that, happy to move on to Q&A.
Great. So as a reminder, if you want to ask a question, just raise your hand. Otherwise, you can send it to me on the iPad. Nobody's done that yet.
Do you want to switch places or say that? Either works for me.
Okay. First question for me on the neuroscience franchise, specifically the oxybate business. How do you think about the long-term mix between narcolepsy and IH?
Dan, you want to take that?
Xywav is off to a great start, as Bruce highlighted in the presentation. Initially with narcolepsy, now being the treatment of choice as of October, having more patients on than Xyrem. Xywav and IH, which is just a bit over a year now in product launch, is a new market, first and only FDA-approved drug. We see substantial opportunity. We've referenced before 37,000 patients who are actively seeking treatment. And so we're in the midst now of promotion as well as medical education to identify the appropriate patients. But we see both of them as being parts of the sustainable and growing Xywav franchise.
How do you think about Xywav's command of the oxybate market as generics and/or branded competition enter?
So Xywav, of course, is the only low-sodium oxybate. Xyrem and now the first AG are both high-sodium. They're not substitutable, of course. And with the FDA, we do have orphan drug exclusivity and a safer product because of its sodium. So we continue to focus our efforts this year on educating physicians about the benefits, reaching patients so that they're informed as well. And for Xywav and IH, of course, it's the one and only approved therapy. So we feel well positioned for the long term.
You know, I'll say for a product that launched just two years ago and just a year ago in IH to be annualizing at north of $1 billion already, we're really happy with our progress thus far. We think we can continue to grow as Xywav across both these markets.
That was my next question. So just to confirm that, can Xywav grow in 2023 through the launch of Xyrem authorized generics?
Yes.
Can you?
Do you want more detail or just?
Go for it.
I think yes is a pretty definitive answer. Again, we continue to see that for patients new to oxybate, the vast majority of them are starting on Xywav, and Rob, you just might want to talk from a medical perspective about that choice doctors will face.
Sure. So from a medical perspective, those patients who are started either because they have IH, Dan pointed out there's no other proven oxybate in idiopathic hypersomnia. But for those patients and doctors who have made the choice to either be initiated on Xywav or to transition from Xyrem to Xywav, given the reduced sodium and the lack of safety concerns around that, supported by orphan drug exclusivity from the FDA, very unlikely from a medical perspective that they would switch back.
Can you walk through how Jazz's royalties on the Xyrem authorized generics are going to evolve?
Do you want to take that or do you want me?
Sure. I can take that.
Okay.
In terms of Hikma, who just launched their authorized generic, there are three stages of the royalties. The first six-month period that we're in right now, we have tiered royalties that are wide-ranging, and they increase to Jazz Pharmaceuticals as their percentage of our oxybate market, including AGs, increases. Starting the second six-month period, the royalties increase to a higher fixed rate to Jazz Pharmaceuticals , where both Jazz Pharmaceuticals and Hikma receive substantial royalties. And then starting one year into the launch, the royalties to Jazz Pharmaceuticals increase pretty dramatically to a high double-digit %. Now, six months after Hikma's launch, as you know, three more authorized generics are able to enter the market. Those are severely limited in terms of the volumes they can sell, unlike Hikma, whose volume is unlimited. Jazz Pharmaceuticals also has royalties on those sales of authorized generics.
What's your expectation for the market share between Xyrem and the Xyrem AG, or I guess in seven months, AGs in 2023 and as we think over the next couple of years?
Yeah, I'm not sure we've got any specific guidance on that. I think Hikma's made some public comments that they expect branded Xyrem will retain a meaningful share. So I don't think it's going to be and everything switches all at once. But you know our strategic focus is all on Xywav. It's all on growing that Xywav business. You know Xyrem, we stopped promoting a couple of years ago. That's a declining business. It's been declining thus far because when we've been competing against it, now it'll be us and an AG, but you know our focus is on Xywav.
How likely is it that Xyrem generics, i.e., not authorized generics, launch in 2026?
That's still a long way away. Obviously, the big difference between the authorized generic launches that are happening now and potential future generic launches would be that the authorized generics can use our approved REMS, our approved distribution system. For true generics to launch in 2026, they'd need to develop their own REMS, their operationalized REMS that would somehow interoperate with the Jazz REMS. Our goal is to make that Xyrem business as small as possible by 2026, I'll just say.
Maybe switching to EPIDIOLEX, how do you think about the drivers of growth for EPIDIOLEX in 2023? What do you think long-term peak sales might be?
Dan?
Yeah, I'd say the first short-term driver is just continued customer engagement. So we were really pleased as we were going into the third quarter and seeing that even more in the fourth quarter. A lot more face-to-face engagement, a lot more offices open, more patient flow, both in Europe and the U.S. And importantly, as we're building the base of prescribers and getting more patients on, you know it's important to have that face-to-face engagement. I'd say the second thing in the U.S. that Bruce alluded to in the presentation is making physicians who are not as familiar with EPIDIOLEX aware of the strong synergy between EPIDIOLEX and clobazam, clobazam being a very widely used agent, where we see in our data that we've got 50%-60% reduction in seizures. And so often going into those offices and asking physicians, do they have patients on clobazam?
Are they all well controlled? If not, are you aware of the data? It's just a great way to get some initial experience and sort of build the base from there. And I'd say the third aspect will be geographic expansion. So we've got France now launched in December. We have additional markets. And then lastly, it will be data generation with Rob's organization, both new indications as well as real-world evidence and additional studies that go beyond just seizure benefit, but look at the broader potential of the agent.
We haven't given a peak revenue forecast. You know we did say it would be a blockbuster product, and we said together with oncology, expect $2.5 billion in revenues in 2025. And we didn't say 2025 would be the end of the growth. We think it can grow from there. So we think it's got really substantial potential. And I should say, you know part of that potential is in continued education of doctors of the broad spectrum activity across seizure types. And Rob, you might just talk about some of the ongoing work we've got to broaden that understanding.
Sure. So we have a trial initiated for EMAS, epilepsy with myoclonic-atonic seizures. This is a rare but important segment of pediatric epilepsy, is about 2%. And so having direct data to support the use in that population will in and of itself be important, but it also gives us additional data in that particular seizure type, myoclonic-atonic seizures, which complements a broader set of data coming from our three labeled indications, but also from the early access program that really shows that EPIDIOLEX is active in a wide range of types of seizure disorders. And I think that ultimately drives its use.
Just sticking with this for a little longer, because I think there have been periods of time where investors are anxious about the potential of EPIDIOLEX. Can you maybe expand or spend a little more time on what you think some of the product's growth drivers are that are underappreciated or not as visible to the street?
So we have said before that it is commercially sensitive. And definitely during the first period that we had the drug, COVID was a limitation. And so getting that face-to-face engagement as well as more patient flow is very important to the drug. I think continued publication and presentation of data and then sharing the peer-to-peer experience that these physicians have. And we saw that in abundance at the AES conference in December. And then lastly, I think it will be this additional data that we're talking to. You know, the good news from a market access perspective is we have very broad and good quality of coverage, and we're continuing to look for ways to improve utilization management. So it's easy for physicians to prescribe and get the drug to the patients who could benefit.
I'll keep going. Switching to oncology, how do you guys think about the peak potential for Rylaze? And what are the most meaningful growth opportunities from here? Is it geographic expansion? Is it those kind of older adolescent patients? Is it silent activation? Yeah.
Can I take that, Rob?
I thought you would just say yes.
Yeah.
You know all of the above. I mean, we were really pleased with a product before Erwinaze. When we started to run into supply limitations, we were running at about $200 million annually, of which 80% was the U.S., and we're already well north of that. Within a year of its product launch, we saw the product really respond well. In part, supply and constraint, quality product, good services, but really a return to best practice where when physicians see the first hint of hypersensitivity on the E. coli-based asparaginase, they are changing over to Rylaze and ensuring you're not risking these pediatric patients with anaphylactic shock and worse when they're going through this regimen, and Rob could speak to this as a prior pediatric oncologist, but I also do think it's going to be the market expansion and the education into the AYA segment.
Rob, do you want to add anything?
Yeah. I mean, I think you touched on all of it, but to be explicit, we're planning for an approval in Europe with a product that we feel is not only better quality, but has a better dosing regimen based on how we studied it. As the experience grows in the United States with this being widely available, we're hoping that there'll be greater uptake into that young adult age group where data shows that when those patients are treated on pediatric-based regimens, they tend to do better. So there's an opportunity to grow there as well. And as you pointed out, there was a reluctance to switch off of PEG asparaginase, for example, not knowing if there would be a supply of Erwinaze. And so we're seeing that practice pattern change to what it was before the shortages.
Longer term, we're excited about growing the asparaginase franchise beyond the current indication as well. Historically, we didn't have enough supply to do significant clinical investigation, but both with Rylaze and with other things in our pipeline, we're exploring broader use.
Can you also talk about the phase II study for JZP385 and essential tremor, what the timeline is for data, and what you expect to learn from that study before moving forward?
Sure. So this study is a phase IIb trial. It's a registrational quality. So the patient population is defined in such a way that it would support registration along with agreed-upon endpoints, which is the TETRAS- ADL and performance scale. It's agreed upon with the FDA. It's evaluating three different doses, once-daily doses, that are based on the prior phase II study. So we expect to confirm the initial proof of concept in a study that would ultimately contribute to registration and to ultimately pick a dose to bring forward into another phase III trial.
We expect that data in 2024.
Should we think about there being a read-through between essential tremor and Parkinson's tremor?
Not a direct read-through. Of course, if it's active in essential tremor, demonstrating that that mechanism is doing what we think it should be doing, I think that has to bode well for Parkinson's disease tremor. But they are different disease entities, and that's why we're studying them separately.
Maybe switching to JZP150 for PTSD, what differentiates that from other products in terms of impact on fear extinction?
So it's a differentiated molecule in that it's an irreversible inhibitor, and so it has the potential to be more potent at the receptor than other drugs that are technically in its class. This is a little earlier in development than JZP385 in that we don't have clinical data in patients yet. That's the purpose of this study. But we do have preclinical data that suggests it should work. And as you mentioned, we evaluated it in healthy volunteer fear extinction model, which has some predictive value for PTSD. So excited about this based on the mechanism. It is an endocannabinoid, so to speak. It raises anandamide levels. And alterations in anandamide levels are known to be associated with PTSD. So there's a strong mechanistic rationale, and that trial we expect to read out this year.
And then maybe last on the pipeline, for the orexin product, I think you mentioned some level of proof of concept data this year. What's that going to look like?
The drug was first evaluated by Sumitomo in a classical rising single-dose healthy volunteer study, which is actually still ongoing in Japan. Leveraging those data, we've initiated a healthy volunteer study where we'll be getting pharmacodynamic measures as well to look to see if it has alerting properties in healthy volunteers. That could serve as a proof of concept and also inform dose selection for patient studies.
Okay.
The trial's ongoing.
We have one minute to go. So I'm going to jump over a couple of financial questions, or maybe one. How should we think about operating margins evolving in 2023 and 2024, i.e., basically between now and when you need to get to the 2025 target or come back to the 2025 target?
Yeah. No, it's a great question. So we set our 2025 target to be 48%, and that was a 5 percentage point improvement from the 43% we had in 2021. If you look at the midpoint of our guidance, as Bruce had mentioned, for 2022, it puts us at 49% already. So the reason that we were focused on really disciplined capital allocation and will continue to do so is to enable us to allocate capital to our commercial launches, the ongoing products that are growing, the pipeline, and continued corporate development. So I wouldn't expect the operating margin to be exactly linear. I would expect to see greater investment across 2023 and 2024, and ultimately in investments that are important to us. And we're very well positioned to hit then the 48% still in 2025.
Great. We are out of time. Thank you, everyone.
Thank you.