Jazz Pharmaceuticals plc (JAZZ) Earnings Call Transcript & Summary

Hi everybody. We're going to be get going here with our next company presenter at the BofA Global Healthcare Conference. My name is Jason Gerberry. I'm one of the biotech and specialty pharma analyst. And I'm pleased to be introducing our next company presenter, Jazz Pharmaceuticals and joining us from the management team, we've got Renee Gala, COO; Rob Iannone, Global Head of Research; and Samantha Pearce, Chief Commercial Officer. So first off, all of you, thanks for coming.

Thanks for having us.

A pleasure being here.

So I don't know, do you guys coming off the quarter, anything kind of prepared you wanted to talk about specifically? Or should I just jump right into my questions?

We'd love to just make a few opening comments, if that's okay. So just to get some of the housekeeping out of the way, and thank you all for joining us as well. We will be making forward-looking statements today, so please consult our SEC filings and website for more information about our business, including risk factors. Should we make reference to guidance, we're not updating today. This is all as of our second quarter earnings at the end of July. And finally, if we reference non-GAAP financial measures, you can find full reconciliations on our website. So maybe just a few minutes about the business, and I'd love Rob to talk about a couple of things in our pipeline. In the second quarter, we were really pleased with our results. We had record revenues exceeding $1 billion in the quarter. We had 15% year-over-year growth across our key growth drivers of Xywav, Epidiolex and Rylaze and then 10% year-over growth -- and year-over-year growth in oncology. So quite pleased with the performance at nearly $600 million generated an operating cash flow over that 6 months. So the business is performing well. Also in the second quarter, we did disclose that we would no longer be providing the financial metrics underpinning Vision 2025, as you're aware. But we also made it quite clear that we continue to drive our business based on those underlying pillars. So driving commercial excellence, revenue growth and diversification, continuing to invest in our pipeline to create more innovative therapies for patients and drive shareholder value and then continuing to be disciplined in our approach to capital allocation so that we're focused on that long-term sustainable growth. And then as we look forward, we're really excited about a few of the pipeline readouts that are coming and maybe Rob, with that, you'd like to cover those.

Yes. I'll quickly highlight some of the more near-term catalysts for us, and I'd like to start with Zanidatamab, which we feel is essentially a derisked asset that has tremendous potential as a best-in-class HER2 monoclonal bispecific antibody. I would start with the fact that since we did the in licensing deal, we've consistently seen additional data that gives us confidence across a host of different indications. Starting with biliary tract cancer, obviously, we had an opt-in once we saw biliary tract data in second line and for best of ASCO in that subsequent year. We've seen 2 separate cohorts of frontline gastric data continued to evolve in a very favorable way relative to like we'd expect for comparators, most recently, those data were updated at ESMO. And we published in breast cancer that makes us feel so we have a clear path in late-stage breast cancer as well. So we now have 3 Phase III ongoing trials, one in biliary tract, one in gastroesophageal adenocarcinoma. In biliary tract, we have a PDUFA date based on the existing data that I referenced to give you an idea how transformational that would be. The response rate was 41%. The duration of response, median duration of 14.9 months. And the early survival data, which we presented at ASCO this year of 15.5 months, which is really unprecedented [ result ]. So we have an opportunity for approval this year, and we have submitted in Europe as well. The gastroesophageal adenocarcinoma frontline, which has the potential to replace Herceptin as the standard HER2 agent in frontline gastric as well as transition to Zanidatamab as the preferred partner for combination with PD-1, where that's appropriate. We are tracking events in that trial and our current projections are about 2Q 2025 and that frontline gastric study. And as I mentioned, the breast cancer program Phase III is just kicked off. I think worth also mentioning our Zepzelca program, which has been, I think, very, very successful second line now becoming a standard in second line. We partnered with Genentech to do a frontline trial, and that trial is expected to be out this year.

Okay. Maybe we can start with some -- just some strategy-level questions first. And in terms of thinking about the portfolio build-out, if you go back a year or 2, people worried about competitive forces that might erode certain monopoly positions in markets like oxybate. We sit here today, you've launched Xywav. I think it's annualizing about $1.5 billion and IH is growth source within that. Do you feel like -- I feel like the markets discount the stock because there's still a perceived necessity to do a deal. As you kind of sit here and you talk about disciplined M&A, I'm just kind of curious how you think about the progress to diversify and solidify the base and then you have some pipeline that you spoke about. Where does M&A ultimately fit in all that? And the fact that you've sort of solidified the base, does that alter, I think, that perceived necessity to do a deal?

Yes, it's a great question. I would say just backing up on the diversification and growth. I started the company in 2020 and that year, we had about $2.3 billion in sales. Roughly 75% of that was coming from that single product in Xyrem. So to fast forward to our most recent quarter where Xyrem accounted for about 11%, Xyrem plus our authorized generics, of over $1 billion of revenue. So on track to deliver between $4 billion and $4.1 billion of revenue in 2024. We really, I think, have done a nice job of both growing the revenue base but also diversifying the business. You don't have one single product in the income statement that's dominating the income statement. So I think that was important for our business. And certainly, with respect to oxybate, with respect to that franchise in general, we viewed it as more durable than I think the market has, and I think have done a nice job in being able to demonstrate the importance of low sodium with Xywav. What does that mean for business development? Certainly, from a focus area, we continue to look at the opportunity to grow and diversify our business using corporate development as an important pillar which it has served for us in the past to help us achieve what we've achieved. And that focus continues to be in sleep, in epilepsies, in oncology but also areas that can be on the periphery. Many of the products that we have today serve rare orphan populations. And there are relevant learnings and capabilities that can be applied to other areas within rare orphan that don't necessarily fit those categories specifically. But that is the primary focus. And we look at both on-market or near-market products, but as well as things in the pipeline. Zanidatamab, for example, came into a licensing transaction, and it's probably the product most we're excited about in terms of potential going forward.

So is it fair to say less of a focus on maybe reducing oxybate as a percent of the revenue pie and more just trying to be opportunistic where you see good assets that could either fit the rare orphan sort of CNS vertical or the oncology vertical?

I would say it should always start for, I would say, all companies and ensuring that you have a meaningful impact for patients, and that is squarely in the center of what we're looking at. I think with the environment you have today, the payer environment, whether it's being able to make progress with changing treatment paradigms, engaging with HCPs, front and center of that mission is ensuring that we have a product or program that we think can have a really meaningful impact for patients. And then we also focus on other characteristics like ensuring that it's an addressable call point, ensuring that we believe we can have -- we can apply our expertise and our overall global footprint. But we're not squarely focused on diversifying away from sleep or oxybate. We're looking at where can we have a meaningful impact, where can we apply our expertise? And ultimately, where do we think we can generate returns for our shareholders.

Yes. And one question I get, given now that we've got a number of quarters under our belt, we can see the impact of the AG. We can see the impact of the branded competitor that's out there. Does that in any way, I don't know, lessen the need for an immediate contributor in any way and allow you to focus more on thinking more long-term? Just wondering what are some of the benefits of sort of how you're seeing the durability play out?

I would say we were probably a little more focused on revenue -- near revenue deals as we were coming out of the GW transaction and delevering quite quickly, but we have never hesitated or never stopped looking at important innovation from a pipeline perspective. There really has been more where do we think we can have a meaningful impact. Where is the science that we think we can really leverage to be able to have that impact? How does it fit within our portfolio. So it's -- I would say the focus is more squarely in that area. And when I look at where have we been able to structure deals that enable us to also manage and balance risk. Zani is an excellent example of that being able to have a relatively small upfront payment that was followed by an opt-in payment based on being able to see the data. And as we think about it now in terms of the data we're most excited about, maybe Rob, do you want to comment?

I mentioned some of it in my opening comments, but certainly, just recognizing that BTC was the faster market strategy is a relative more limited population. The data that have emerged in gastroesophageal adenocarcinoma have really been strong. There have been 2 cohort study. One by Zymeworks that was initiated by BeiGene, where Zani was being studied with chemo or on the BeiGene side with the additional test [indiscernible]. And those cohorts have been independently very, very strong. So for example, response rates that are in the sort of 80-plus percent range relative to standard of care, Herceptin chemo of 96%, really durable responses. So 18-plus months into the sort of incrementally 22 months when they had tislelizumab and PFS, where you'd expect across 3 different studies, Herceptin chemo, like 6.7 to 8.1 months. We're seeing now on the updated date of 15.2 months, 16.7 months in the distant cohort. So we think demonstrating not only that we have a really good shot when we read out the Phase III trial next year is projected, it also speaks to the differentiation of this HER2 agent and the applicability in other settings such as breast cancer. And we think, therefore, there's potential that goes way beyond these 2 near-term.

Yes. So I think how the best way to ask this question. So a lot of investors have wondered about the -- having oncology and CNS under one group. Other companies have made the decision strategically to kind of break those apart. If Zani data are as strong as you hoped you would -- and you're not getting credit in the stock, right? How are you guys thinking about sort of the idea of keeping these 2 businesses under one roof and especially if the markets aren't coming around to that because a lot of people will say to me, I think there's a lot of trapped value with the oncology business right now in Jazz proper. And so I think Zani data will put that truly to the test next year when you do put the Phase III data card. So just curious if that's a thought process at all with the management, the Board in terms of keeping these 2 businesses together.

Well, we'll always look at ways that we think we can generate the best returns for our shareholders. And so if we come to a conclusion that large structural changes are needed in our business, that we wouldn't shy away from pursuing that. I do think that the company has changed and transformed so much over the last several years in terms of expanding, diversifying the commercial footprint, expanding the pipeline and now being in Zanidatamab, development and not hesitating to expand into, for example, breast cancer, which is not an area we've been in before, but one that we're advancing the Phase III study in because we think that's an area where we can have a meaningful impact. So I would say we'll continue to look at what makes the most sense in terms of the business following the science and the data. But I would also reference going back to a prior point on a number of our underlying patient populations. Being rare and orphan there are more similarities between these 2 areas in terms of where we are playing than what there may be differences in terms of the underlying blocking and tackling field execution as well as the patient support services when you're looking at these smaller populations. And there's the other benefit because we also focus quite a bit on corporate development, augmenting our business and augmenting our pipeline, when oncology is hot and there are strong valuations that we think aren't where we want them to be from where we want to play, we can look at areas of neuro and vice versa. So having some further diversification between the TAs has helped us over the years. But if we reach a conclusion that that's not the case, we would certainly not hesitate to make changes. We just haven't reached that conclusion.

Understood.

Jason, maybe what I would add, I think there's a lag in appreciating the potential Zanidatamab in the investor community relative to what I'm experiencing, I've been doing cancer research for more than 20 years in the industry alone. I would say there's a disconnect between what the KOLs are telling us, they're seeing the doctors who are using Zanidatamab in the clinical trials or reading about the data and helping us to develop a strategy and development. Really as soon as we in-license this. I was getting calls from especially the breast cancer community saying, we think you need to go here. And so a level of interest, excitement around Zanidatamab amongst physician scientists who have been using the drug and amongst those who want to be developing it is -- as high as for any drug that I've ever worked on KEYTRUDA, Imfinzi, Trodelvy amongst others. So I think there's a little bit of a lag. And I don't know whether it's going to take turning the card in gastric community -- but the scientific community is [indiscernible].

Yes. Let's talk about Zani and the update at ESMO. In terms of kind of key takeaways, it seems to us that maybe the PFS improved a little bit, so maybe the margin for error on the primary registrational endpoint has a little bit more cushion. I guess the other thing we've observed in some competitor studies is that the ToGA regimen seems to maybe be doing a little bit better than the original study. So maybe how do you kind of distill down the learnings of ESMO as it pertains to that frontline GEA study and your confidence that will hit the registration endpoint?

Well, what's convincing to me for Zanidatamab is how consistent the data are across all of the different studies with -- we will start with cross indications no matter where this studied, whatever tumor type, if HER2 is overexpressed Zanidatamab works. And it almost doesn't matter whether it's with patients who are naive to HER2 therapies, or those who have already progressed on multiple lines of therapies, which is often the case in breast cancer. The other thing that's convincing is that in multiple studies within a certain indication, you see the results being replicated. So the first observation that led Zymeworks to go after BTC was from the Phase I trial. Now it's all 20-some patients. They set up the pivotal program and recapitulate. And the durability is an impressive piece. So the longer we follow those studies, the data hold up. Same on the gastric side. I think it's important, as 2 separate cohorts, one started by Zymeworks, one started by BeiGene, different centers, et cetera, showing highly consistent results that are at least in a cross-study comparison, I recognize a lot of patients there, are much better than what you'd expect. So Jason, you mentioned the standard of care Herceptin chemo, there's been a little bit of an evolution in terms of what you might expect, how you might expect that to perform in 2024 versus 10 years ago. It's been a small evolution. I mean, that range is like 6.7 to 10.1 -- I'm sorry, 6.7 to 8.1 median PFS. What we're seeing in our single-arm cohorts is 15.2, 16.7 in those 2 independent cohorts with incrementally better tislelizumab. And if you look at other measures of efficacy, it makes sense, right, because the durability is so much longer. The response rates are better, but we're really differentiates is on the durability, very well-tolerated drug that patients stay on and resistance doesn't emerge as quickly. So in those cohorts, we got 18.7 months net incrementally [indiscernible] months with the addition of tislelizumab. So I think that the emerging data continue to give us confidence about Zani being the cornerstone of therapy -- gastroesophageal adenocarcinoma. We're studying both gastric and esophageal some of the studies like [indiscernible] just gastric. The cornerstone HER2 therapy regardless of the patient population. And some people have said, how do you think about PD-L1 positive or PD-L1 negative? PD-L1 status is not a predictor for efficacy of HER2 therapy. So Zani will work well, whether you're PD-L1 positive or PD-L1 negative. What's emerging is in those patients who are truly PD-L1 positive, they will benefit also for PD-L1 inhibitor. Now how is that defined. The approval is in anyone with 1% or higher according to CPS with the [indiscernible] assay. But we're not even clear whether that's the right cutoff. And I think our data as well as other data field will sort of help define who is going to be best to get Zani chemo who would benefit from the addition. There is a in-license [indiscernible] BeiGene has Asia, except for Japan, and we have rest of the world including.

So when you're going through these trials as the BeiGene [indiscernible] building up. Is there any -- are there any issues where you've got 3 [indiscernible] any ambition is why is that you got the structure to the [indiscernible] because that's how [indiscernible].

So at the time that we in-licensed Zanidatamab, shortly thereafter, we made a decision to bring the Zymeworks employees who were working on Zani over to Jazz. So that's been simplified. There's not like a JDC structure with Zymeworks employees to control that development. We looked very carefully at what they put together and actually it was a pretty smart strategy. Fast to market with BTC, trying to own gastric cancer by going frontline given the data they had. So we were quite pleased with what they've done. The one tweak that we made, and we understand why they did this. They were going for speed with their frontline gastric trial. So they wanted to keep the sample size down. And so it was very well powered for progression-free survival, but not as well powered for overall survival. And they're thinking there is that maybe overall survival wouldn't be important if you had strong PFS data, and they wanted to go for a faster readout and to enroll more patients and push that time. When we looked at that, we said we think we can have our [indiscernible] too. We think that the health authorities will allow us to maintain the timeline for PFS, do that on a subset of patients and then enroll additional patients who would contribute to the overall survival so that we can also increase our power and precision around the survival, which I think is now becoming more important as you see KEYNOTE-811 data where they have survival data that we would be compared to. So we made that one tweak. We changed the sample size. We think that's now a much better powered study. It still gives us a chance at an early look at OS because with those additional patients, we'll look at OS at the time of PFS that will be very mature and not likely to hit. We'll still look at OS when they had planned to as the second interim, and then we'll have the full mature OS later on. So we made those tweaks, and then thereafter, the development program, the design of the breast cancer program, that's ours. As for the other party, it's been a great collaboration with BeiGene. Their CMO is someone that I worked and actually hired to AstraZeneca when I was there work very closely with Mark Lanasa. They have a great team. It gives us capability that we don't necessarily have. So in collaborating with them on that gastric trial. We have boots on the ground in places like China, which is you need to have, you're going to do a quality study in China. And we've actually leveraged that collaboration even for the breast cancer program to allow us to enroll what we think would be quality sites in Asia that could also help speed. So it's not as complicated as 3 parties. It's now really 2 parties where our roles are delineated and we think it's actually a productive relationship. We're looking to do more.

As you go deeper into [indiscernible]. And do you see yourself more about [indiscernible]?

Well, I can answer this, but [indiscernible].

Yes. I mean we're building this commercial, we're ready to launch in BTC and [indiscernible] you already had a solid tumor field force in the U.S. So we're leveraging that capability we already established that augmenting it further so that we were able to launch successfully into this market. One of the great things that we've experienced actually until we get ready for the launch is just how attractive Jazz is because of this asset, because of the culture that we actually do have at Jazz as well, which is a talent [ magnitude ]. So we've been really excited to see the capabilities within the PDUFA date in November, so that [indiscernible].

I mean maybe the only thing I would add from an R&D perspective is throughout my 20-year pharma career, it's really easy to recruit people when you've got a drug that people are excited about, and that has been the case with Zanidatamab. Retaining the people from Zymeworks, bringing in the new talent that we would need to work on this certainly from an R&D development and medical perspective. And I know that you've had the same experience as I said earlier.

Which indication whether...

I mean, my answer to that is similar to what Renee said earlier, which is we want to go after population where there's a significant unmet need. Where we think we can make a meaningful difference. We don't want to be a me too. We don't want an incremental benefit. And we want to work in places where we can be successful as a Jazz, which has evolved quite a bit since 5 years ago when I started, for sure. I think we have much more capabilities in areas that maybe aren't appreciated from the outside. And I think we are a much more credible partner for those kinds of in-licensing acquisitions, partnerships, collaborations. So I think I wouldn't want to pin us down to a simple answer around that. But I -- case by case, and we've spoken around the near-term catalyst because, obviously, those are things that are top of mind for people. But we have invested in earlier areas where we think with a small investment in a short amount of time, we can create a major inflection. But take, for example, on a early oncology pipeline, we've been investing in the MAP kinase pathway, which through additional discoveries and advances in chemistry, we now think can be better targeted. So we have a pan-RAF inhibitor in the clinic through a partnership with Redx Pharma, with whom we're also partnering on a KRAS program, two targeted areas in KRAS, KRAS-G12D and KRAS program. And we think there you could have a rapid inflection in certain high unmet need areas like pancreatic cancer, where 90% plus of KRAS mutated and a great majority of those are KRAS-G12D. And so have we worked in pancreas before? No. But we have something that's truly transformational, we'll want to pursue that. And we'll weigh our options in terms of how to partner either on the development side or -- I wouldn't necessarily narrow the opportunities in sort of general way.

Along those lines, you've guided to Zani being about a $2 billion between the 3 indications, I think, BTC, GEA and breast. I would assume GEA is a pretty meaningful proportion of that number. Just to confirm, I think there's about 5,000 to 10,000 U.S. patients that have that HER2 amplified on breast cancer profile.

So when you look at the market more broadly because we're looking at U.S., Europe and Japan, you're looking at around 63,000 patients. In the U.S., we see about 8,000. So to your point, breast is the largest opportunity, more than 150,000 and then GEA. And then as [ Sam ] had mentioned, BTC is smaller, but it's our first entry point.

Yes. And as I think about data scenarios for GEA, the one thing I struggle with is if you -- with your doublet arm, show really good data, even strong relative to KEYNOTE-811 in terms of PFS profile. Why the market wouldn't just consolidate to doublet what's the rationale for going to a triplet in that scenario? And so I guess the question really is how much incremental benefit do you feel like the triplet arm needs to show in perhaps a subset of patients to be the approach for some versus consolidating the market back to doublet therapy?

So the 2 components are [indiscernible] component and Herceptin maybe I'll take Herceptin. Ultimately, Jason, it depends on the data. And you're right, if it doublet is as effective as triplet why would you add the third drug. That's not really what the science is telling us. Remember, this is still really poor prognosis. There's a lot of headroom here even with the substantial advances that have been made. And so what I'm expecting is that Zani will become the backbone for HER2 therapy. And that will be substantially clinically meaningfully better than Herceptin and chemo. For those patients who truly have upregulated PD-L1, we know that what's happening in those patients is the immune response to that tumor is being blunt. And if you can take the brakes off there, you're likely to get incremental. Again, does that define the way Merck is defined? I suspect what we've not been optimized. And so does that mean a good splits 60-40 or 50-50 and 40-60, you will be able to determine that to some extent from our study. But I do believe based on the current science that there are going to be patients who you can determine through a biomarker test, whether they would benefit from the additional therapy. And that's why we -- again, I can't take credit for it, but that's why we really like the design of the -- of the Zymeworks study to have that second exposure.

Maybe just...

And then sorry, from a regulatory perspective, you do have to show contribution of components. In other words, to win, we need the doublet needs to be standard of care, but the triplet to be approved that not only has to be the standard of care, but it has to be better than the doublet to your point. The FDA hasn't necessarily defined or other health authorities. They haven't necessarily defined that as a being stat sig or being meeting a certain level, I think it will ultimately be a review issue based on the risk. But it will have to be better. And we'll look at some, right? It may turn out to be only better in those...

Sure. Okay. And then another ESMO question, just like in ENHERTU as a competitive threat does come up a lot. They had some data at ESMO not sure if you saw that data. And had any thoughts. There were several treatment arms. It seems like they maybe have some combinability issues. One arm had like 50% dropout rates, another arm had really profound PFS. So just how do you kind of contextualize the ENHERTU competitive threat?

Yes, and it really depends on which tumor type you're talking about, so I can step you through it. With respect to those data, I do think it tells you something we already know, which is ENHERTU is a way of delivering chemotherapy. So inherently, your ability to combine naked antibody like Zanidatamab, which has a really unique way of shutting down growth signaling and a unique way of triggering the immune response. The combined ability of Zanidatamab is going to be much better. And the tolerability of Zanidatamab as a monotherapy is going to be better. So in those settings where you can't carry the risk of a 2% risk of death -- toxic death, pneumonitis or otherwise, such as the curative setting. Something like Zani is going to be a bigger advantage. In terms of how we view ENHERTU as competition. So in BTC, there's no specific approval for our HER2-directed therapy in BTC. Zani will be the first one. As you know, ENHERTU have a pan tumor indications. So technically, it can be used in the U.S. in BTC. If you stack those data next to each other, Zani actually looks better in every respect, efficacy-wise but certainly from a tolerability perspective. So in second-line BTC, I expect Zani is going to be very competitive. In frontline, we have an ongoing -- just opening a clinical trial there, and we'll be able to demonstrate. Second line ENHERTU has been positioned -- sorry, in gastric ENHERTU has been positioned as a second-line therapy. And the data you saw last week, our exploratory Phase II. So we are really ahead of that, expecting the pivotal trial to read out this year. We've said based on the current projections 2Q next year. So we're really out ahead of them, and we expect to be able to be a leader, whether it's combined tislelizumab with [ Zanidatamab ] and chemotherapy. The breast cancer space is where I get the most questions around how do you navigate in a space where there are what, 5 HER2 agents approved. But what we're learning is that ENHERTU has really been a game changer there. And it's not like the other drugs. It's likely to be effective enough to be ultimately used in frontline. And the big question in the field for anyone who hasn't heard our R&D Day, I encourage you to listen to it and listened to the breast cancer experts who spoke about their experience with Zani and spoke to the development plan for Zani in breast cancer. There's a big question in the field. The patients who progressed -- breast cancer patients who progress on ENHERTU, what should be the favorite HER2 therapy. We know for many, many years of research in this area and the patients must get additional HER2 blocking of some sort. The resistance despite whatever the mechanism of resistance, you need to block HER2. So they need to get a HER2 agent. The problem is none of the other agents where ever studied in a population who had progressed on ENHERTU will be the first in that space. And that's why we moved so quickly into that area because of the way the treatment landscape. So in a sense -- ENHERTU is not a competitor there either because we're going to follow it. And what's unique about breast cancer is, fortunately, these patients, while they have terminal illness in the metastatic setting, they do have a prolonged survival and have the opportunity to see many lines of therapy. So there are probably as many patients getting third line setting. And so we have an opportunity to come in after ENHERTU. So in all of those places, we found a way to either be differentiated based on the safety profile, and we'll move into earlier stage of disease where that will be better choice, we think or to find some white space in the way that ENHERTU has been developed. The rest of the competition is further behind. I think for me, if I'm thinking the long-term, the competition is not ENHERTU its the next generation. But again, they're further behind. And all you're seeing there is Phase I, Phase II. So they're not in registration.

Okay. So in the last 5 minutes, just a couple of quick hitters on the commercial business. So maybe starting with oxybate, about 3,000-ish patients, you're adding a couple of hundred a quarter. So that's like something like 10% penetrated into a TAM you guys have defined for IH. Is this -- do you drop parallels to the narcolepsy launch where it's just the sort of kind of slow, smoldering, continued progression, I think about competitor drugs like WAKIX like they just seem to consistently add a couple of hundred patients a quarter. I'm wondering how to think about IH because it is the primary sideway growth driver going forward. And so I'm wondering if my characterization of that is accurate and your confidence level to keep kind of just building that patient base at the pace that we're at?

Yes. I mean you're right. IH is focus and for a good reason, obviously, Xywav is highly differentiated as the only low-sodium oxybate on the market, and IH is differentiated that no other product has [indiscernible] differentiated. And we're seeing -- there are clear variations quarter to quarter on average, we've seen around 275 net patient [indiscernible]. And we're seeing good response to some of the investments that we're making. We expanded the field force in IH to get more breadth across from other [indiscernible], but those who prescribed oxybate before, but also those that are new to oxybate as well. And we're also investing in nurse educators so that can really help doctors and patients start patients on treatment get through the titration and then importantly, obviously keep them on treatment. And once they get through that initial phase, we find that patients can stay [indiscernible] effect. And so yes, we expect to see that continue. As you mentioned already, the market is very large, and it's a really underdeveloped market currently. There's a lot of patients out there and around [indiscernible] or so that are diagnosed and seeking treatment, but many more of those actually undiagnosed as well. So really...

And then on the orexin program that it sounds like there's a potential to revive this program and identify appropriate therapeutic window without the QT interval prolongation. Has that been internally understood and characterized? Should we expect an update on the 3Q call as it pertains to that program? Just anything you can say on that front?

So what we've done so far with that program is evaluated in mostly single dose like in limited cohort, multiple dose healthy volunteer studies. It was in the single dose where we really pushed the dose high trying to get a maximal effect in a sleep deprived healthy volunteer model, where we saw the cardiovascular effects that we mentioned as well as the visual disturbances. What we've learned from the field is that in the context of, NT1, in particular, the exposures required to get efficacy are lower than in sleep deprived healthy volunteer. So if you just look at what's the dose that Takeda selected for their NT1 trial or Alkermes. I think it's maybe a -- so we want to essentially evaluate a lower dose, where we think there would be a therapeutic index to the cardiovascular toxicity and see what we get. The beauty of it is with this mechanism, you don't need a lot of patients. So we certainly thought it was worthwhile doing limited about that patient study to fully characterize that. And you will find out we may determine that this is not a best-in-class molecule that we're not bringing forward. We don't know yet. But I think in the process, we learned a lot about the mechanism that could be informative for our backup program.

Final question from me. As it pertains to Epidiolex in the ongoing patent litigation, there were a number of filers, but I just wonder if they're paper ANDAs, right? Like do you know if anyone's actually committed the investment to be able to manufacture botanical source material, which is kind of what the FDA has guided to. I imagine during the litigation process, you get some line of sight into what the ANDA challengers actually have. But just curious if you can comment at all on that.

So I would say there are both botanical and synthetic challengers. But stepping back and looking at Epidiolex, we have a robust patent estate, more than 20 Orange Book issued patents. Also when you think about our claims and how we've asserted those in this ANDA filing process, they also cover both botanical and synthetic and our method of use patents cover all of the approved indications. So we feel quite confident with respect to that patent state. But above and beyond that, this is not the type of investment process know-how that you would normally see a generic going into when it comes to -- as it pertains to botanicals. So for example, there -- this is a bespoke manufacturing process, GW Pharmaceuticals who, of course, we acquired would be received Epidiolex had invested over $100 million in the equipment, some of which was customized to be able to produce Epidiolex. There's know-how with respect to growing with respect to growing. And so this is not typically the profile of the type of investment that you would see a generic going after. So while we can't comment specifically beyond that, I would say we do feel a level of confidence with respect to that long-term durability of Epidiolex.

Okay. I think we're at time right? Well, thank you guys so much for joining us.

Thank you very much.