Jazz Pharmaceuticals plc (JAZZ) Earnings Call Transcript & Summary

Good afternoon, everyone, day 1 London Healthcare Conference. Very factoring, we should have done a bigger room. Jazz is a hot ticket for sure. For those who don't know me, my name is Akash Tewari. I'm a pharma biotech analyst here at Jefferies, and I have the pleasure of hosting the Jazz Pharmaceuticals management team. Joining me today, and they will be giving some brief introductory remarks will be Renee Gala, President, Kelvin Tan, Chief Medical Officer; and then Samantha Pearce, Head of Europe and International. I'll give it -- I'll hand it over to you for some introductory remarks and we'll get started.

Sure. Yes. Okay. So just a reminder, we will be making forward-looking statements today. Please see our website and SEC filings for more information about our business. Should we refer to guidance, we're not updating or reiterating today. This is as of our earnings call last week. And then finally, should we refer to non-GAAP financial measures. You can find full reconciliations on our website. So thank you for having us, Akash. We're thrilled to be here. And I'm probably most energized by not only the crowd in this room but also by just the overall transformation of our business over the last several years. I joined the company in 2020. That year, we had $2.4 billion of revenue and 75% of that was coming from a single product in Xyrem. Fast forward to last week at our earnings, we had 16% of revenue coming from Xywav -- sorry, Xyrem and the authorized generics of Xyrem, and we're on track to do over $3.8 billion at the midpoint of top line revenue. So considerable growth but also diversification, and we're now looking at a diverse, durable portfolio on the commercial front. That's also put us in a position financially where we have a strong balance sheet, $1.6 billion of cash at the end of Q3. We generated over $900 million of cash flow in the first 9 months of '23, and it's placed us in a strong position to be able to continue to invest in the business, in particular, in the growth drivers of our business: commercial, the pipeline and corporate development. 2023 has been a transition year for our oxybate franchise. We've had considerable uptake of Xywav and narcolepsy and in idiopathic hypersomnia despite the entry of 2 authorized generics at the beginning of the year as well as the branded high sodium fixed-dose competitor coming onto the market. And importantly, across our 3 growth drivers, Xywav, Rylaze and Epidiolex, we had collective growth of 24% compared to the third quarter of last year. So really strong business performance. Moving on to the pipeline. 2024 is going to prove. I expect to be a very exciting year for the company. We have up to 5 late-stage readouts coming across 2024, all with differentiated compounds that are going after areas of significant unmet medical need. In January, we expect to read out 150 in PTSD in the first half of next year, 385 and essential tremor. In the second half of next year, our Epidiolex study in Japan, which we expect to serve as registrational material for that geography. Also in the second half, our Zepzelca study in first-line extensive-stage small cell lung cancer, which gives us the opportunity to expand and grow that franchise. And then finally and probably most excitingly zanidatamab in GEA in first-line therapy in 2024 as well. So that's the 5 late-stage readouts planned for the end -- for 2024 in addition to Orexin agonist, initial proof of concept before the end of this year. So just stepping back, an incredibly rich catalyst-driven value inflection point driven year ahead of us in a very strong position from a commercial perspective, and well capitalized to continue to invest in the business. So we'll turn it over to you, Akash.

Thanks so much, and I really appreciate it. So I'm going to start off with, it was a pretty funny headline back in October from Bloomberg. Jazz exploring alternative options, including sales. Now I'm not going to obviously ask the very obvious question. But I think the underlying issue, I think I hear from a lot of investors is, it seems like Jazz is not always a great use of people intellectual capital. They'll tell me like, oh gosh, I'm going to spend 2 weeks trying to address model sodium oxybate. . And I still don't have a ton of confidence on 2025 growth, right? Or Zepzelca, like is it going to get pulled off the market? Is it going to hit ARON's confirmatory trial. So I guess the question becomes Jazz seems to be a story that always resonates more as a free cash flow story. You guys always generate a lot of free cash flow. It doesn't seem to resonate for some of these like mid-cap public equity growth managers, right? So how does that problem kind of get solved over the next few years with Vision 2025 and then even kind of beyond that because I feel the story has moved beyond '25? And the number two is, are you considering strategic alternatives? And if so, what are some ways that you feel like you might be able to unlock value?

Yes. So maybe I'll take the second question first, and I'll just reiterate what our mentioned on last week's call, which is we don't comment on rumors or speculation. We've been very clear about what our investment priorities are. We've been quite disciplined from a capital allocation standpoint and investing for growth. And so that really turns us to the first part of your question, which is how to think about Jazz in the next couple of years. And certainly, I mentioned that we've had a year of transition for the oxybate franchise this year in 2023. And we have met every element of 2023 with execution. We have seen this market play out largely in line with our expectations. We gave neuroscience guidance at the beginning of the year. We reiterated our guidance last quarter after having increased that top line guidance in the second quarter. So I think that's largely playing out. And I also would expect, as we look forward to 2024, in particular to our sleep franchise will continue to see Xywav be the oxybate of choice in '24 and going forward. With respect to other elements in terms of why invest in Jazz, what's exciting about that. I just mentioned the incredibly rich pipeline that we have, in particular, going into 2024. So the story has evolved to so much more than a commercial story of execution. It's now evolved into a commercial story and an innovative biopharma R&D pipeline story and in particular, with sanidatumab, which I'm sure we'll get to, which we think is a complete game changer, not only for patients with HER2-positive cancers but also for the company.

Understood. Now maybe just to bridge off of that. A question I get -- and this doesn't just apply to Jazz, I get it from neuroendocrine as well. There's this idea that there's a lot of CNS -- there's not that many actual commercial stage mid-cap products. There's a lot of commercial infrastructure that's been built out. There might be room for someone to consolidate there, right, whether it's a merger of equals or you start partnering especially, I know maybe in Europe, there -- Epidiolex, you start your footprint in European CNS, but maybe you can build out on it. So when you think kind of strategically -- there's a lot of options available on the chessboard, but do you feel like there is room for consolidation maybe in the CNS space? And are there places where you feel like you could, in particular, leverage some of your commercial infrastructure in order to get kind of value-add deals where they're like plug-and-play, they directly start contributing to your bottom line EPS growth.

Yes. I would say we're in a great position to be a buyer. We have been very active and engaged in terms of looking at opportunities as part of our Vision 2025 targets. We have a placeholder for corporate development. Maybe I'll turn to Sam in a moment to talk about our footprint, Europe and international in general because we do believe we have the opportunity to continue to optimize that. But I would say, as we've approached corporate development, we also are being quite disciplined. We have no interest in doing a bad deal. We have 0 interest in overpaying for assets. So we think we've reached a point where we are very much a partner of choice. And if you look at recent launches, whether it's Zepzelca or Rylaze or the work that we've done with Xywav, the commercial execution has been demonstrated there. So you want to talk about Epidiolex and Europe international?

Yes. I'll just say a word or 2 about the region in general because I think part of that transformation has been about transforming into a global by a pharmaceutical company. So over the last 8 years or so, we've built really strong infrastructure across 2 franchises, hematology oncology and now obviously epilepsy as well. And we are poised as a result of that in all of the key geographies in Europe and the key markets outside of Europe, to not only optimize the portfolio that we have in our hands today, for oncology, but zanidatamab. We're ready for the launch of Zanidatamab with strong capabilities. And we're still growing very nicely across the U.S. and Europe with Epidiolex as well, still with a number of opportunities to penetrate the market further, not just in pediatric, but in the adult setting, but also continuing the rollout of Epidiolex to other important markets, as Renee said, for example, in Japan, with the data readouts next year.

Understood. Now, Renee, your question actually, it makes me think like I feel like in some ways, with your Vision 20 -- like it's 500 million in revs, BTC, second line, third line is probably $50 to $100 million by them, right? It's not going to be a huge component of that $500 million. Like your guidance almost pigeon holds you to a very like select set of CNS deals that can contribute that amount of revenue by 2025, right? . And to your point, you don't want to overpay, you're not going to do something that's a bad deal for shareholders, right? So how do you kind of balance doing a CNS deal that hits that guideline that you guys put out versus making sure it actually fits, right? What's most important for you guys, right? And how committed are you to that M&A part of your Vision 2025 target?

Yes. So -- well, stepping back, why would you include a target for corporate development in a 2025 vision. Well, given the history that we have of corporate development being a really important pillar of growth and diversification for us, we put out that marker because we didn't want people to assume, we were just going to sit on the cash and not put it to work. If you look at the transactions we've done in the last, say, 3 years, we closed the Zepzelca transaction in 2020, that's generated over $800 million in revenue for the company, highly accretive transaction. We closed the GW transaction, which was transformative for us as a company. Not only did we acquire Epidiolex, but we also acquired multiple capabilities that enabled us to have full end-to-end R&D capabilities as well as the cannabinoid platform. And then moving into 2022, closes Zanidatamab transaction, which we think really is transformative for us. So we didn't want people to forget that we have a history of doing diversifying revenue growth transaction and pipeline expansion transactions. Now you've talked about neuroscience a bit, and I just want to clarify, we're not just looking at neuroscience. We have said we're interested in neuroscience and oncology, to continue to leverage our current footprint, which is now global, as Sam had mentioned. But we're also looking at rare and orphan opportunities. The vast majority of our products fit into that category. And there's a level of learning that transfers to rare, orphan diseases and orphan call points outside of neuro and oncology. With respect to have we pigeon hold ourselves, again, just stepping back, we think we're well positioned for growth. That's our focus, growth, continued diversification but also having the focus on really meaningful opportunities to change patient care to meaningfully impact it in areas that we think we can leverage our expertise to go after.

Understood. Now maybe turning to sodium oxybate. This was something -- I know I got from investors, we were kind of chewing on as well. You guys are on track with your guidance. I don't think there's any doubt. There's a slight miss on xywav at least versus sell side consensus and Xyrem was a little light as well. And then at the same time, you have comments on LUMRYZ where they're saying, we have 1,000 new patient starts, and they seem to be insistent a lot of those patients are coming from Jazz [ ResMed ]. Our survey work suggests that actually -- it seems like both products, Xywav and LUMRYZ can kind of coexist in the market. And then number two, there seems to be an enormous amount of refractory sodium oxybate patients. So there are patients who were on a Jazz regimen and they either go back to a Jazz regimen or they try something different. So let's just start in terms of clarifying how much switch is -- switching are you seeing vis-a-vis, a, Xyrem and the generics to, let's say, a once-nightly product. And how much switching are you seeing directly on Xywav in narcolepsy to a next-gen product? It seems like there's a difference in commentary between both companies here.

Yes. Well, maybe just starting with the difference in commentary, we're also in terms of what we're reporting, not reporting the same thing, just apples and oranges. And if you look at what Avadel reported in the third quarter, they reported new patient starts. They referenced the discontinuation rate. But I think of that as a growth number, the 400 patients based on what they described. Whereas, with our Xywav patient numbers, we're reporting something that's more akin to a net number. We know there are discontinuations in oxybate therapy. You do have to change lifestyle preferences in order to start that therapy. So what we report are the number of patients on therapy at the end of the quarter that reflects both ads as well as discontinuations. So it is a difference. Our focus is on Xywav. Our focus is on continuing to have adoption across narcolepsy and idiopathic hypersomnia. We've seen a lot of a lot of news resonating in terms of with HCPs. I'll ask Kelvin to comment on that in a moment about the benefits of sodium as well as flexible dosing and individualized dosing. And then I think your question was, can these 2 products coexist? Absolutely. And we see, over time, whenever there are multiple products in a market, that additional marketing out in the offices at HCP's talking about an indication will by default expand the indication patient set. So we do expect patients to drive to a fixed dose, high sodium branded competitor. We just don't think that's the majority of patients. We do believe Xywav will continue to be the oxybate of choice. And maybe, Kelvin, you'd like to comment further.

Yes. I mean so Akash, you've heard us speak many times about the benefits of low sodium, and that's why we believe Xywav is the treatment of choice for any patient who's taking a high sodium oxybate as well. But recently, we published data at World Sleep, looking at not just the -- not just population, but the IH population as well, which again confirms that in the IH population, they too have an increased risk of cardiovascular disease, but they are -- they have an increased risk, of course, of developing hypertension cardiovascular disease, et cetera. So this is very important for us to remember that there's a long-term opportunity for narcolepsy and IH patients to benefit from a low sodium treatment. Now if I might just turn to another point, though, we continue to hear from physicians and from patients about the benefits of individualized treatments so because Xywav is dosed twice-nightly because you can give asymmetric doses, you can give a higher first dose and a smaller second dose. It allows you to individualize your treatment to the patients need, whether that's because you're waking up early because you need to catch bus, you've got an interview, you're trying to look at your children. All the things that we think about in our daily lives, that's the one key benefit you get from twice nightly dosing is the opportunity to individualize your treatment. And that's something that we think is going to be important, and we continue to hear from physicians.

Okay. I'm going to make a not a -- we're tangent, but you talk about [ invite ] dosing. You're orexin agonist, right? I feel like your commentary has been -- I don't know what this whole talk about potency is. We have a different scaffold, we're not going to show liver tox. We're going to get to the therapeutic window that we want to get to. And then you're looking at other -- orexin in terms of MWT as a proxy, it seems like you can get to adequate exposure. The question -- I'm kind of true over when we look at your compound. Are you going for acuity regimen or of the ID regimen? And would there be a benefit from potentially -- just as you mentioned, in sodium oxybate, an orexin that gets BID because then you can -- 1 bullish dose kind of like what to get assume with A-61, and then another one to kind of deal with increased sleep pressure in the afternoon, but then you don't have any residual levels at night, right? So is that something we're thinking about for your Orexin program?

So that's a great question, Akash. And there are a number of hypotheses in there. What I would say is when we reflect on the data that came out from World Sleep, I think the one thing I would share with you is it really reinforces our confidence that orexins are likely to be complementary to the use of an oxybate. That's what I think we're now seeing is that we saw some of the data presented, which indicates that if you don't get that half-life right, if you don't quite get that dosing right. You run the risk of generic getting insomnia later into the evening. Now that's something clearly we don't want to have. So the balance between the 2 treatments orexin agonist and an oxybate, I think is probably where the market is going -- where we will find ourselves, which is they're complementary that oxybate treat the underlying issues, the sleep architecture are rather place in the daytime, is it once daily? Is it twice steady? What is the right dose, et cetera. These are all the things that are going to become clearer. And whilst the data, I think, are encouraging. I would again say, it's very early days. We, as Jazz have been very clear, we're not going to share the data from our ongoing clinical trial. We do have a comprehensive Phase I studies, as you know, single ascending dose and multiple ascending dose studies. And as we said, by the end of this year, we will achieve -- we will know that whether we've got proof of concept in our sleep deprive healthy volunteers, and what you'll see from Jazz rather than a flurry of publications and data is more likely to be us progressing or not into next stage depending on the outcome of what those data show us.

Yes. Now this is the one thing that's -- you guys have the pot of gold, right? You have the $2 billion market, right? You look at Takeda and Alkermes. And since Alkermes is the same question, why present the data at World Sleep, it's competitive market. Yes, Akash, we need to show this data so that we can actually enroll a trial because we think speed is very, very critical here. I never -- that's the one thing I don't get. Why not talk more about it, given that you have a market leader position if you do show good proof-of-concept data, right, wouldn't that help you enroll a trial more quickly? Why not be more towards coming with that? .

So again, great question, Akash. We are the leaders in sleep medicine. We've been in this industry now from nearly 20 years. We have great confidence in the design of our trials. We have great confidence in our -- in the studies that we're running and the information that we're going to gather from that. It's our choice, it's our decision that we've taken, which is we're not going to be showing that data. It doesn't -- please that we read into anything around company who's got confidence in our program and how we're going to take it forward.

Yes. And I might just add to that, that it's been immensely helpful to people direct developing orexin agonist to be able to see the data that Takeda published and then to be able to see the data from World Sleep that Alkermes has published. In particular, they've seen path lights. it seems to be relevant in terms of insomnia. So I'm not in a competitive space, in a competitive field. I'm not in a hurry to share detailed data about our compounds that may inform others' development, but I'm certainly grateful that it's out there.

Understood. Okay. By the way, it helped us. Okay. Understood. And now maybe on JZP-150. I think I've had 3 people on my team. I spent a weekend. We all end up being like I just stand out. It's like a -- it's very, very hard to have conviction into that study. But you've made comments that were really interesting because like CAPS-5, there's a lot of variability on that PTSD endpoint that we've seen in our analysis. But you -- I don't know, it was you or someone on the management team, I think it was in the last 2 quarters made a commenting like actually, we feel pretty comfortable about the range of CAPS-5 at -- I think it's either a 12- or 16-week endpoint that you -- for your data that's coming out. Help me, I know this is selfish that maybe not for everyone else, but in terms of variability on CAPS-5 and what you expect from a placebo response in the population you're looking at, any color on how you were envisioning that to play out?

Yes. So I'll take a step back again and I'd reflect. We're very confidence in the design of our clinical trial. This was based upon Phase II data from T-CALM as well as our interactions with the FDA, which gave us confidence around how we would select our endpoints. We've got a well-powered study, which is designed to show statistical and clinical significance. We're recruiting up to 400 patients. As we said before, we will execute that study, and we will have the data by the first half of 2024, another late-stage readout. We do recognize that neuropsychiatric trials where you have a placebo, there is always the risk of a placebo effect, but that's why we come back to confidence in our clinical design with those 400 patients with a robust 12-week assessments of CAPS-5 versus baseline that we believe our study is adequately designed and powered to show a difference versus placebo on -- and in particular, clinical and statical significance should the study read out as we would like to think it will.

Understood. Now one thing -- it's interesting, when you look at the J&J compound, it seems like you get to a dose response pretty quickly. There's no clear dose response with the J&J compound, like the low dose and the high dose both get ANA levels that max out. But there does seems to be an issue of duration of inhibition throughout the day, right? And that's where maybe the Pfizer, SpringWorks, Jazz, now Jazz compound may differentiate there. And you also talked about like the low dose, you get full inhibition, just at the end, it feels out in the high dose gets full inhibition. So how important for you scientifically is it to get FAAH inhibition throughout the entirety of the day? And do you think that will differentiate from what we've seen with maybe the earlier J&J compound?

Yes. Again, a great question. Akash, you've obviously be doing a lot of reading. The way that we think about this is that our FAAH inhibitor is highly differentiated, as you said, irreversible binding. Therefore, you get a differentiation of action versus other FAAH inhibitors. A lot of the questions you're asking, I think we'll start to understand as we progress through our trial. I would just wanted to share that we have great confidence in our execution, and we continue to deliver on that. And as I said, those data -- we fully enrolled that trial and the data for our FAAH inhibitor will be our top line data in January '24. So again, a good example of Jazz R&D executing.

Okay. Last one, if I can sneak it in. October, ZW25 data versus Keynote-811. It was a 76% versus 75% response rate, but there was a real differentiation on median PFS, right? 16.7% versus about 11 months and there is no -- obviously, no survival benefit. What's going on there? Right, like a, why is there a difference between the triple? And then it looks like the doublet might actually even have better data. And then number two, what is your confidence? Is that early PFS signal actually holds up in a larger study for GEA?

Yes. So Keynote-811 has been important in terms of our understanding and our thinking about how we progress forward. What I would say is what it's clearly identified is that KEYTRUDA's benefit is in the PD-L1-positive patients. We believe there's a big unmet need -- urgent unmet need in the PD-L1 negative population, which we believe Zanidatamab can address, in particular, because our doublet has shown significantly better -- you should do an intercompany into a trial comparison, but really encouraging [ CR ]. So we believe that, that means data has the potential to replace trastuzumab as the standard of care. As well as that, in our GEA study, we do have a PD-L1 inhibitor. So our triplet includes zanidatamab, tislelizumab as well as chemotherapy and the BeiGene release data, ESMO, which I'm sure familiar with, which again was very encouraging in terms of objective response rate, 76% approximately versus, again, what we're seeing in other groups.

I'm over time, I appreciate you guys being patient. Thank you so much, everyone, for joining us and Jazz. Thank you.

Thank you. I really appreciate it.

Thanks for the call.