Great! Well, thanks everyone for joining us. I'm really excited to be joined by the management team of Jazz. Bruce Cozadd, Chairman and CEO, Philip Johnson, CFO, and Kelvin Tan, CMO. Thank you all.
Glad to be here.
Bruce, maybe I'll turn it over to you for some opening remarks here. You know, set the stage for us.
Sure. So happy to be here today and give an update on progress of Jazz Pharmaceuticals. I will say before I start all the exciting stuff, I'll make forward-looking statements. You'll be glad to know I'll be making forward-looking statements. You'll see our risk factors. We'll refer to non-GAAP financial measures. There's always a reconciliation to GAAP on our website. And what's the other thing I wanted to say? Oh, man! Oh, if I refer to guidance, which I probably will, it's as of the day we gave it on May 1st. Okay, with that exciting part out of the way. So we feel like we're well positioned to achieve our objectives for 2024. We reported our first quarter results, and we saw 12% combined growth of our major growth drivers, XYWAV, EPIDIOLEX, and Rylaze.
We saw double-digit growth, 13% of our oncology business first-quarter-over-first-quarter, and our largest product, XYWAV, grew 14% first-quarter-over-first-quarter. That all makes us confident that we're on track to hit our revenue guidance, which was $4-$4.2 billion, or 7% growth at the midpoint. We're making big investments behind our commercial products and our pipeline, and I'll let Kelvin talk about some upcoming milestones there, but excited about our progress. And then financially, we're very strong. Ended the first quarter with $1.8 billion in cash, cash flow from operations in the first quarter, $267 million. So good start to the year for the first quarter. We're confident about our guidance for the full year. And Kelvin, maybe you could mention some upcoming milestones.
Sure. Yeah, so 2024 is gonna be a very exciting year for Jazz, in particular in R&D. We've got a number of near-term milestones which are expected this year. So let me start with zanidatamab. Zanidatamab is perhaps, you know, we would absolutely say it's our most de-risked asset, with the potential to transform the treatment of HER2-expressing cancers, and could be as much as $2.5 billion to us in revenue. So if I start with zanidatamab and biliary tract cancer, you would have heard that we were pleased to hear that the FDA gave us a priority review for zanidatamab as monotherapy in second line, uh, BTC, and set the PDUFA date for the twenty-ninth of November. So we could be commercializing very soon after that point.
With regards, BTC, we shared some data at ASCO just last week. It was really well received. We shared our first mature data for OS in zanidatamab, achieving overall survival of 15.5 months, 18.1 months in the IHC 3+ population. So that was really impressive, and went down very well. And we also filed our MAA in Europe, so Europe will be following suit. Turning to GEA, so gastroesophageal adenocarcinoma, we have a frontline study ongoing now that is slated to read out with PFS at the end of this year. And then for breast cancer, we've just moved into the metastatic breast cancer space. We've opened up a program there, and we hope to initiate our phase III study in late-line metastatic breast cancer for zanidatamab in the second half of this year.
Sticking to oncology, so for Zepzelca, we're very pleased with the progress we've had on our frontline trial combined with Tecentriq, and that study is due to read out at the end of this year, perhaps into beginning of 2025. Moving on to neurosciences. So EPIDIOLEX is doing very well for us. We have a phase III trial in Japan, and we expect to get top-line data from that in the second half of this year. We also have suvecaltamide, and so that's a very near-term catalyst for us. We'll be turning that card imminently. So suvecaltamide is our T-type calcium channel modulator for the treatment of Essential Tremor. So those are the headlines, and as you can tell, Andrea, a very busy year for us.
So many things you just covered there. But, maybe we can start on your commercial business here.
Sure.
As you think about the XYWAV business, that I think there's been a lot of focus on the sustainability of, your sleep-wake disorder business. Maybe help provide some context for what gives you the conviction that XYWAV and that growth profile is sustainable on the forward?
Yeah. So we are commercializing XYWAV in both narcolepsy and idiopathic hypersomnia. The narcolepsy space we've been in for a couple decades now, idiopathic hypersomnia, much newer. And while we're seeing growth in both, we're really investing behind growth in idiopathic hypersomnia. On the narcolepsy side, we continue to be the oxybate of choice, the only low-sodium oxybate, and treaters and patients are appreciating the importance of low sodium in the narcolepsy population that's known to be at high cardiovascular risk. XYWAV is a differentiated product from any other product out there, not AB substitutable with the generics, and we believe has lots of growth in front of it. In idiopathic hypersomnia, we're the first and only approved agent for the treatment of idiopathic hypersomnia, a very large market opportunity that we're certainly in the early innings of.
When we combine what we're doing with that nice growth that I mentioned in XYWAV, with some legacy XYREM-branded sales, with substantial royalty participation in AG versions of XYREM, we've said that royalty income should exceed $200 million this year. Overall, when we add that up, we're convinced this is a very sustainable franchise.
... What are you seeing as the competitive landscape has rapidly changed over the last couple of years, how has that gone, maybe relative to your prior expectations?
Yeah.
What do you maybe anticipate on the forward?
Well, I'll remind people, we gave guidance for 2023 before that competition emerged, right? We gave guidance before there was an AG on the market. We gave guidance before there was a branded high sodium competitor. We actually raised our neuroscience guidance on the revenue side during 2023 and hit that. So I would say last year, things turned out very much the way we thought they would. We obviously had a little more visibility into that competition as we gave our guidance for 2024, and we feel very confident. We're happy with how we're doing there, particularly as you saw our first quarter patient adds across both narcolepsy and idiopathic, idiopathic hypersomnia. So a total of 12,950 patients coming out of the first quarter, very much on track with our expectations for the year.
Maybe speak to EPIDIOLEX here. You guys have been doing and undergoing additional data generation. How meaningful has that been to the community and the impact then as it flows through to potential sales?
Yeah. So EPIDIOLEX has been growing very nicely. We're on track for this to be a blockbuster product by 2025, as we had said a number of years ago. We're seeing growth coming from the U.S. and ex-U.S. markets, even before we get to the Japanese data that Kelvin mentioned earlier. Fueling that growth is real conviction about what EPIDIOLEX can do, and some of the newer data we've been sharing over the last couple of years has contributed to that excitement about the growth potential of the product. Data on combination seizure reduction with clobazam, where you're seeing 50%-60%, depending on whether you're in Dravet, TSC or LGS. Those kinds of seizure reductions are really unprecedented in these conditions. People are responding well to that, but they're also responding well to the beyond seizure benefits of EPIDIOLEX.
I think a lot of that conviction was there even before we shared some of the data we've shared about improvements in cognition and behavior, as noted by caregivers. We actually have ongoing studies now to fully flesh out that data in a more rigorous fashion. But I think people appreciate the efficacy on the seizure and beyond seizure side. They appreciate the tolerability of the agent. They appreciate the fact that patients stay on therapy for a very long time, and we continue to see opportunities to grow that in new markets as we move more into the adult population. These are childhood onset seizure disorders, but obviously people grow up with these disorders into adulthood, and we think we're not as penetrated in that adult population. So lots of continued opportunity for growth.
When you think about that expansion into Japan, maybe help provide some context for what that incremental opportunity is. Then as you think about the data read that's coming in the second half of this year, maybe any areas of risk, or should we feel pretty comfortable here given what you've seen in prior trials?
Yeah. So in terms of market opportunity, we think there are about 20,000 patients in Japan across the three labeled indications. In terms of the phase III trial, it is across all three of those indications. I think the regulators in Japan understand we have lots of data on EPIDIOLEX already, so this is sort of additive data that would be combined with data already in existence to support a regulatory filing there. But I will say the epilepsy community, particularly KOLs in Japan, is very excited to add this treatment to their armamentarium for these really difficult to treat diseases. So, excited to make the product available to patients as soon as we can.
You know, maybe one of the questions I had around this trial is that the inclusion criteria, maybe like the background therapies that patients could be on, vary between U.S.-based trials versus this one. I guess, how should we think about that?
Yeah, we noted that as well. I mean, you know, when you think about any of these global trials, there are often differences, nuances between how diseases are treated in one country versus another.
Yeah.
So we recognize that. But as Bruce was saying, we have a significant body of information. We've got five global trials, a significant body, and this is really a relatively modest study, which is bridging from the Japanese patients back to that, to give confidence that what we've seen in our totality of data, is gonna be replicated in, pediatric and a small number of adult patients in Japan. And as Bruce was saying, they're very excited with that study as enrolled fast. There's a lot of engagement from the sites and investigators. They really want to bring this to their patients.
Great. I wanna turn to zani, since, as you mentioned, your most de-risked asset. You have a PDUFA date later, at almost the end of this year. Just remind us the differentiation here. What gives you the conviction as you think about launching in second-line BTC, that you will really be able to gain a foothold there?
Yeah, that's a great question, and it's something I always like to bring everyone back to, which is the fundamental reason why we believe zani is going to be successful, and that's because of its differentiated mechanism of action. So zanidatamab is a bispecific antibody, but it's different in that it has biparatopic binding. And what that simply means is it binds to two different non-overlapping epitopes on HER2. Now, that means it binds in trans across two different epitopes, ECD2 and ECD4, which is actually where pertuzumab and trastuzumab bind typically. So imagine you're binding to both of those across two non-overlapping epitopes. So we believe that's one of the reasons why you get that very unique clustering of the receptors, which then leads to multiple different mechanisms of action, whether that be immune-mediated phagocytosis, complement activation.
That's probably one of the most differentiating factors, is the way that, through, zanidatamab, we get complement fixation and activation. But that's why we're so confident is when you then see the flow of information that's been coming over the last 18 months, literally the flow of data as we're releasing, it's giving us increasing confidence that actually zanidatamab's underlying mechanism of action is translating into the clinic, is translating into clinical practice. And some of the data that we've shown, for example, for BTC, is unprecedented. And I use that word carefully, but is unprecedented in terms of the overall response rate that we're seeing in BTC. 41.3% versus standard of care, which is about 22%, so almost double that. And then that effect is being seen, as we presented our data at ASCO this year.
So not only did we present data that was a year more mature, we were able to show that the mean duration of response was extended by two months to 14.9 months, that the overall survival was 15.5 months in the ITT population, but 18.1 months in the IHC 3+ population. And the response that we got from our KOL community was that they really felt that this was very, very different. And that's why we have this belief that zanidatamab could really transform the treatments of HER2 expressing cancers.
What will it take, maybe from an infrastructure standpoint, as you think about launching into this indication? Is your existing sales force sufficient? Do you need to build it out? How much education? I mean, clearly, the data set's been out there, but how much education is required here?
Yeah, so we think we're really well prepared to do a successful and rapid launch of zanidatamab into admittedly this targeted group of patients. Our existing infrastructure is significant in the relevant place. The target audience is limited in size. We may add some resources at the margin, but not a significant increase from where we are now. So, you know, I would just point to, we've had a couple launches in oncology over the past few years that have gone very well with Zepzelca and Rylaze. We're confident we have the right team to go after that initial BTC opportunity, but then behind it, to be ready to go with GEA, should we unblind positive data as early as the end of this year.
You know, we would expect that data to be picked up in NCCN guidelines, and maybe to even see use of the product before we get to what hopefully will be a rapid sBLA review by FDA.
Maybe on that point, you, you have always talked about BTC being the starting point to launching you into frontline GEA, into breast cancer, potentially into other indications. Maybe help remind us what evidence you've seen there. What does give you the conviction as you, as you look to these upcoming data reads or potential trials that you're running, to, to give you conviction that this really, you know, will have a meaningful place there?
Yeah, well, let me just start by reminding people of the markets we're going after in terms of size. So we think there are about 12,000 BTC patients, HER2 expressing, if you combine U.S., EU5, and Japan, sort of the major markets. As we look at GEA, it's a much larger opportunity. The comparable number would be about 63,000. And obviously, as we move into breast cancer, you know, a much bigger opportunity, 150,000 plus. So, you know, we see this opportunity to grow the impact of zanidatamab over time. Kelvin, maybe you could talk-
Yeah.
A little bit about GEA confidence.
Yeah. So, you know, I've already spoken about BTC and the data that's already given us confidence there, and as we said, moving into GEA, one of the things that has really given us the confidence is the early data that we've seen that's been coming through. So some of the data we have for the doublets of zanidatamab plus chemotherapy, compared to the existing standard of care, which is essentially the ToGA regimen, has been very impressive as well. So again, you know, objective response rates as high as 79%, long durations of response, PFS, as well of about 12 months as well for the doublet, and then for the triplet, so zanidatamab, plus chemotherapy, plus the PD-1 tislelizumab.
Again, that data that has given us, again, confidence that the GEA frontline study, you know, really we should be optimistic about what those results are gonna look like. Because in that—for, for the triplet, we're seeing objective response rates of 76%, and we're seeing PFS of about 16.7 months. So if you compare that to what you see, as the sort of the standard of care now, which again, would be KEYNOTE-811, you'd say you should be encouraged, and so—and we believe that we're optimistic about that. We do also have data in breast cancer as well, later lines of breast cancer.
I touched upon some of the data that we have, which shows that even in later lines of therapy, even in patients who have been exposed to TDXD as well, we're seeing objective response rates of about 35%. We're seeing PFS of around 10, 10, 10 months in some indications and 12 months in others. We've even got data in a triplet combination, which is chemo-free of zanidatamab, palbociclib, and fulvestrant, in HR positive, HER2 positive populations. And it's that body of evidence, that's what I was describing before, about that totality of information, that data flow, which is giving us confidence now to move into metastatic breast cancer with the EMPOWER phase III trial that we hope to have initiated in the second half of this year.
But we do also have plans. Sorry, we do also have activities ongoing in early breast cancer as well, including in the neoadjuvant and the adjuvant space, including collaborations with MD Anderson, with the I-SPY platform. And this is really what's giving us that confidence that we need. We will find our space, that zanidatamab really does have the potential to transform the way that HER2 cancers are being treated.
Maybe to that point, I mean, these indications that you're mentioning here, they're incredibly crowded. And the treatment paradigm itself is shifting so rapidly. How do you think about that in the context of your development plan then? Where exactly will zani fit in, as the landscape changes?
That's a great question, and, you know, maybe metastatic breast cancer is a good example of that. So when we designed the EMPOWER study, this is the phase III study of zanidatamab plus chemo versus trastuzumab plus chemo in the later lines of treatment in patients who have previously been treated with Enhertu. What we were thinking was we had to think about not just today, but what's gonna happen in the future. Taking its place in the market, it's definitely finding its place. We predicted that actually it's more likely to move into the frontline setting. And so there's a really important clinical question that everyone's asking around: So what comes after Enhertu?
Now, one of the reasons why we have the confidence, and we want to answer this important clinical question, is because some of the late line data that we have actually is in patients who have been previously exposed to Enhertu. So again, that gives us confidence that we're thinking about the future. We're planning our programs, looking towards where the market is shifting and playing two, three, five years out. That's, you know, that's complicated to do, but actually it's based upon that foundation of confidence that that underlying mechanism of action is already translating into clinical data that we're seeing.
I'd encourage people, if you haven't listened to the recording of our R&D day on zanidatamab to do so. Part of the reason I encourage that is to hear from the independent investigators that are so interested in this. You mentioned crowded space. We think we have some of those top docs in the space wanting to lead our trials because of the opportunity they see with zanidatamab.
And maybe one more here. As you think about the frontline data that's coming later this year, help frame expectations around what you could see, what would be clinically meaningful. Is the clinical bar different than the commercial bar here, the regulatory bar? What would help support a path to approval?
Can I take that first?
Yeah.
So, so let me just remind you, first of all, so the frontline trial in GEA has got three arms. So it's trastuzumab and chemo as a control, zanidatamab plus chemo, and the triplet of zanidatamab, tislelizumab and chemotherapy. So when you think about in that frontline space, so obviously with KEYNOTE-811 reading out, there are questions around, well, what about the PD-L1 negative and the PD-L1 positive population? So when you think about the PD-L1 negative population, that means that the ToGA regimen still remains the standard of care. And actually, as I was sharing earlier, we're very confident when we look at what we've already seen for zanidatamab plus chemo, it's a doublet, that we do expect to see a significant improvement over that regimen.
Then you think about whether triplet, and I shared earlier that I think, you know, what we've seen earlier for the triplet combination is also demonstrating some benefits over what you see from KEYNOTE-811. What this really tells us overall, though, is that irrespective of what the PD-L1 status is of these HER2-positive patients, we truly believe that zanidatamab has an important role to play, will replace HER2 targeted therapies and really become that standard of care. And our confidence increases as we continue to see data emerging, data becoming more mature. That's telling us that actually, that mechanism of action really is translating into clinical benefit.
Maybe in the interest of time, we can jump over to suvecaltamide, data card flipping imminently here. Help frame your expectations into this data readout. Obviously, Essential Tremor has been a very difficult space.
Yeah. So, we do have a phase II-b trial for suvecaltamide, which will be reading out imminently. Three doses, 10 mg, 20 mg, and 30 mg versus placebo. It's a large, 400-patient, robust, well-controlled, and well-designed clinical trial, which we believe has the opportunity to be pivotal as well. Now, we did a lot of work when we were thinking about this primary endpoint, and I know that's a question that a lot of people are asking: What is the bar that you're trying to achieve? I'd start by saying the composite endpoint that we're using of TETRAS- ADL, which is activities of daily living, and the performance subscale, which looks at domain six and seven around handwriting and Archimedes scale circle. That was based upon the information that we got from our phase II trial.
So we have the benefit of having a, the T-CALM study, a phase II trial, which has helped us to inform our, our decisions around what that primary endpoint should ... discussions and conversations with the FDA, we landed on that as the primary endpoint. Now, we believe that's importantly very patient-centric. It's really getting to the heart of what is it that really matters to patients, the activities of daily living, the ability to wash, to dress, to feed. These are the things that we're gonna look at, but we'll also look at the totality of the data as well. So when we look at and how we've designed this trial, again, 400 patients is a significant study....
We'll look at not just statistical significance, but we'll also look at all of the other endpoints that we've collected in that trial to understand what is it that we need to determine makes clinically relevant impact, and then we'll take that into our decisions around what hopefully the phase III trial then looks like.
Got it.
And I'll just say in terms of comparison here, there really is no effective treatment for Essential Tremor today. Propranolol is the agent that's used most often. It doesn't have significant impact on patients, and so they're really looking for something that will address, as Kelvin said, their ability to live their life.
Maybe just one point of clarification. When you, when you said it was a pivotal study, you do still expect to run a phase III post this? Like, this would not be sufficient for-
We do, but having designed a well-controlled, large study, we do believe it could form part of a pivotal package.
Okay. And if you think about the T-CALM study, which, you know, I think as you mentioned, formed the basis of a lot of these decisions on how to advance here, or sorry, the T-CALM to the study. How do you think about the differences that existed other than the endpoint, right? There's dosing differences, there's formulation differences, even the patient population, slightly different. What do you think is most likely to positively impact the outcome here?
That's a great question, and I'm not sure that we'll ever get the answer to that one, because I think it's about that multifactorial piece that we did. So the way that I think about it is, you know, we looked at the data, and we've made an informed decision looking at all of those different things. So we changed, you know, we looked at the formulation. We went from a twice daily to a once daily dosing. We went from a 20 mg a day to a 30 mg a day to try and increase exposure. We went from a relatively small, short study to a 400-patient, 12-week study, which we think also gives us the opportunity to see that benefit.
So I'm not sure that we'll ever tease out exactly what it is that hopefully will make that difference, but I think what we have the benefit of is learning from what we saw before, learning from, feedback that actually using video rating of the primary endpoints in the original phase II study was probably not the best way to look for those subtle differences, for example, in three-dimensional movements, et cetera, that you see with tremor. And so taking that totality, again, putting all that information together, is what's informed the decisions to how we designed the study.
Maybe let me ask you one more late stage, clinical program question. Zepzelca for frontline, also one where you have a near-term data read coming. Maybe help frame that, that data set, your expectations into it. What gives you the confidence here that you will be able to see a clinically meaningful benefit?
Yeah, I mean, we're really pleased with the way that Zepzelca's really been taken in the community and established itself very clearly as that second-line treatment, and in part because of its robust efficacy, its tolerability, and also just the ease and use of Zepzelca in the community. And so one of the things that we believe is gonna be important is that it has a different mechanism of action compared to Tecentriq, which is an IO. And so we believe that complementary mechanism of action is gonna be important. We've also seen some in vitro data, which is suggesting that Zepzelca can change the tumor microenvironment, can cause tumor suppression as well.
All of that together is giving us confidence that when you look at some earlier data as well, that we've seen some data which indicates that you can combine Zepzelca with an IO in the clinic. All of that together is giving us confidence that this is a trial which hopefully will demonstrate significance because of that different complementary mechanisms of action. And so this is a frontline trial, frontline maintenance in an extensive stage small cell lung cancer, expected to read out towards the end of 2024, if not into 2025. And I think given the fact that it's in maintenance, it will also be a really important opportunity for us to move into frontline space because those patients are gonna get their treatment for longer as well.
It's a really important catalyst for growth for us as well.
Maybe I can continue there. As you think about the evolution of the space, obviously Amgen just had Imdelltra approved. How do you see the evolution of that space? Clearly, they are also talking about going to earlier line settings. You will presumably be competing against them. How do you maybe maintain your, your moat at, in that landscape?
Yeah. So, you know, tarlatamab, again, has a very different mechanism of action. We have to remember, small cell lung cancer is a horrible disease with less than 10%, five-year overall survival. So you know, let's be honest, for patients, we welcome the fact that there's gonna be new treatments. We do believe, though, that because of the very different way in which they're used, that we will find our space and they will find theirs. What we understand as we hear from the community is that they really appreciate that Zepzelca has good efficacy, tolerability, but actually is very easy to use in the clinic.
Recognizing that many of the patients with small cell lung cancer are actually treated in the community, we hear from physicians regularly, they really appreciate that it's easy to use, there's no monitoring involved, and actually, they find that it's good for their practice and their clinics as well. Whereas tarlatamab has demonstrated its profile, and that's why it's got its approval. But let's remember, they do have complexities as well in terms of requiring inpatient stay. There's complexities around cytokine release syndrome, neurological impacts as well. And so that's why we think, for us, the focus really has to be in the frontline space. That's why we think there's much more of an opportunity there. With 30,000 patients who are in the frontline small cell lung cancer space, 27,000 of them are already being treated.
And a significant proportion of those, about 70%, excuse me, 70% of those, we think will be eligible for a treatment in the frontline space for something like Zepzelca. So we see the frontline space as really being the opportunity for us, and that's why we're so excited about the readouts at the end of this year.
I'm just gonna add on to this. Kelvin mentioned the sense from clinicians and clinics that it's easier to use. This is really important from the patient perspective, too, right? Horrible prognosis for this disease, particularly as you're moving to second line treatment. The idea that you can come in once every three weeks for an infusion rather than sort of living your life in a treatment setting really has a benefit from a patient quality of life perspective.
Maybe in the last couple minutes, we've discussed so many different programs. We've not discussed a lot of programs 'cause you have so many, but you do have these two verticals, whether it's the neuroscience, the oncology. As you think about the forward, how do you think about balancing one against the other? What - maybe what area are you most interested in, and which do you believe, you know, really will drive that longer term growth?
I'm gonna give you two answers on this one, mine, and then I'm gonna let Phil jump in on this one, too. You know, I would just remind people, we've been in the neuro space about 20 years. We've been in the oncology space about 12 years, and when we talk about balancing them, my goal is for each of them to be as successful as they can be. And so you're seeing us from a commercial perspective, from an R&D perspective, and a corp dev perspective, continue to invest in both spaces.
We've got important opportunities in both spaces with the current portfolio and pipeline, and certainly on the corporate development, area, as Louis has mentioned, see opportunities to continue to build our business in each of these. Also, we benefit to having both of these verticals. There can be ebbs and flows in innovation in a given space. There are often ebbs and flows in pricing and deal terms that are available to us in a given space. So having the flexibility to look at opportunities in both neuroscience and oncology is important for our overall strategy.
So as you think about corporate development, because that, that does make up, you know, $500 million of your Vision 2025 goal that you've put out there, how are you thinking about deals? Are you looking for maybe later stage assets that can fill... You know, they can bring on revenue in a, in a more near-term fashion? Are you looking for earlier stage, where that return on investment could be greater, you know, maybe more similar to some of the more recent deals you've done?
So first stage, we're looking at both of our therapeutic areas for sure, as well as looking at select opportunities in other orphan or rare diseases, where we can apply some of the knowledge and capabilities that we have. We do look across early stage to later stage. I would say in general, there are probably more opportunities to create more value over time when you take on some additional risk by acting earlier in the development of a drug. So certainly, that has been a priority, very similar to what the company has done with the licensing of zanidatamab, to then have some of that risk get played out over time, so far favorably for us, and see really good value coming from that kind of a transaction.
I would say we're not only looking at acquisition. We'll continue to look at licensing opportunities, like we did with zanidatamab, as a way of building the portfolio and creating value for patients and value for shareholders over time.
Maybe in the context then, as you do think about, about corporate development here, remind us where things stand from a balance sheet perspective. You've talked about being able to deliver very quickly post the GW, acquisition, but is there an optimal leverage profile you're, you're trying to hit?
In terms of optimal, we haven't publicly stated anything. Currently, we feel very comfortable operating where we're at. Just as a reminder, coming out of the acquisition, we've been, I think, at 5.9x leverage. Had a goal by the end of 2022 to get down to 3.5x net leverage. Exceeded that by about six months, and currently stand about 2.4x leverage. We certainly feel like we can operate at this level. There's opportunities for us to pay down debt with our term loan B structure that we have, if we decide to do that with some of our excess cash flow.
We also know that if we decide to pursue a business development opportunity that we see as particularly attractive, like we did with GW, we can go ahead and flex up on leverage with a very well-articulated plan to deleverage quickly, like we did in that case.
Where would you feel comfortable going to with your leverage profile?
It's a great question. It's a hard one to answer, because it does depend on the asset that you're acquiring or the company that you're acquiring. Is it something that's actually generating cash flow or will in the near term, or is it one we're gonna have a longer investment before you get to positive cash flows? And that has a big impact on the amount of leverage you probably want to take on in that acquisition. But certainly, something like GW is very feasible. We have a good history of dealing with that kind of leverage and deleveraging quickly to get back to a position where we're now able to do more PD.
It's not about how high we go on the leverage for a microsecond, it's getting back down to comfortable leverage very quickly that matters to us.
Okay. Awesome. Well, with that, thank you.
Thanks.
Everyone, for joining us.
Thank you.
Thanks.
Thank you.
Yeah, of course. I feel like it's been forever since we saw each other and-
Thanks. Nice to meet you.
It's nice meeting you.