Jazz Pharmaceuticals Q4 2023 Earnings Call Transcript

Quartr
Provided by Quartr
February 28, 2024

There are 14 speakers on the call.

Operator

Good afternoon, ladies and gentlemen. My name is Abby and I will be your conference operator today. At this time, I would like to welcome everyone to the Jazz Pharmaceuticals 4th Quarter 2023 Earnings Conference Call. Today's conference is being recorded and all lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session.

Operator

Thank you. And I will now turn the conference over to Andrea Flynn, Head of Investor Relations. Ms. Flynn, you may begin.

Speaker 1

Thank you, operator, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its Q4 and full year 2023 financial results. The slide presentation accompanying this webcast is available on the Investors call today are Bruce Cozad, Chairman and Chief Executive Officer Rene Galla, President and Chief Operating Officer and Rob Unone, Executive Vice President, Global Head of R&D. On Slide 2, I'd like to remind you that today's webcast includes forward looking statements, such as those related to our future financial and operating results, growth potential and anticipated development and commercialization milestones and goals, which involve risks and uncertainties that could cause actual events, performance and results to differ materially from those contained in these forward looking statements. We encourage you to review the statements contained in today's press release, in our slide deck and the risks and uncertainties described in our SEC filings, which identify certain factors that may cause the company's actual events, performance and results to differ materially from those contained in the forward looking statements made on today's webcast.

Speaker 1

We undertake no duty or obligation to update our forward looking statements. As noted on Slide 3, we will discuss non GAAP financial measures on this webcast. Descriptions of these non GAAP financial measures and reconciliations of GAAP to non GAAP financial measures are included in today's press release and the slide presentation available on the Investors section of our website. I'll now turn the call over to Bruce.

Speaker 2

Thanks, Andrea. Good afternoon, everyone. Thank you for joining us today to discuss our Q4 and full year 2023 results and our excitement about 2024. I'll start on Slide 5. 2023 was a highly productive year for Jazz.

Speaker 2

Thanks to the passion and innovation of our talented employees around the world, we helped more patients, generated more than $3,800,000,000 in revenues and advanced multiple pipeline programs. We believe these accomplishments position us well for success in 2024 as we focus on commercial execution and accelerating top line growth, delivering on key pipeline catalysts and remaining active in assessing corporate development opportunities to drive growth and value creation. Before we move on, I want to highlight our announcement from last week that Phil Johnson is joining Jazz as our Chief Financial Officer effective March 1. Phil comes to Jazz from Eli Lilly, where over the course of almost 3 decades, he led several finance functions and was most recently Group Vice President of Finance and Treasurer. As we move into 2024, we are excited to add Phil's industry experience, leadership and strategic approach to our executive team.

Speaker 2

Turning to Slide 6. Our performance in 2023 is reflective of the strong execution that's transformed our business over the past several years. Highlighting a few commercial accomplishments in 2023, combined revenue from our key growth drivers, Zywave, Epidiolex and Rylase increased 27% year over year. We drove more than $1,900,000,000 in revenue from our sleep therapeutic area, reinforcing our confidence in its durability. Epidiolex continues to grow, reflecting strong underlying demand and the execution by our commercial team.

Speaker 2

Epidiolex is now annualizing at more than $900,000,000 and on track to deliver on its blockbuster potential. Our oncology therapeutic area surpassed $1,000,000,000 in revenue for the year with Rylais leading the way with 40% year over year growth. Moving to our R and D and pipeline efforts, we have multiple near term late stage catalysts targeting significant market opportunities. Given the strength of clinical data to date across multiple indications, we view zanidetimab as our most derisked asset with more than a $2,000,000,000 peak potential. On the operational front, our disciplined capital allocation provides the financial strength to invest in our continued growth and diversification, while generating healthy operating cash flow and margins.

Speaker 2

We have a strong track record of successful corporate development and remain focused on evaluating additional transactions. Turning to Slide 7, we made progress toward Vision 2025 based on our strong performance in 2023. On the commercial side, we've executed successful launches with leading therapies in narcolepsy and epilepsy and a growing oncology portfolio. Our investments in R and D have expanded our capabilities and the breadth and depth of our pipeline. And on operational excellence, disciplined capital allocation has put us in a strong financial position and we continue to be mindful of making investments with the most impact to drive meaningful shareholder value.

Speaker 2

I'll now turn the call over to Renee to review our commercial performance, after which Rob will share an update on our R and D progress. I'll provide a financial overview and then we'll open the call to Q and A. Renee?

Speaker 1

Thanks, Bruce. We had a strong 4th quarter, generating quarterly revenue of more than $1,000,000,000 for the first time. This capped off a successful twenty 23 in which we achieved year over year double digit growth across each of our key products, XYwave, Epidiolex and Rylase. I'll start on Slide 9 with our sleep therapeutic area. Total revenue from sleep, which includes ZYWAVE and XyremNet sales, plus royalties from high sodium oxybate authorized generics or AGs, was $483,000,000 in the Q4 of 2023 and exceeded $1,900,000,000 for the full year.

Speaker 1

We believe we are well positioned to achieve our Vision 2025 goal of $2,000,000,000 in sleep revenue. ZYWAVE revenue was $337,000,000 for the Q4 of 2023 and approximately $1,300,000,000 for the full year 2023, which represented year over year annual growth of 33%. We have increasing visibility into oxybate market dynamics since the entry of branded and AG high sodium oxybates in 2023. We remain confident in the durability of our sleep therapeutic area and XY Wave in particular. As the only low sodium oxybate and the only therapy approved to treat idiopathic hypersomnia or IH, we expect Zywave to remain the oxybate of choice, including the number one treatment for narcolepsy.

Speaker 1

Exiting 2023, there were approximately 9,525 narcolepsy patients taking XY Wave. Our focus is on educating patients and prescribers around the lifelong burden of high sodium intake for narcolepsy patients. Based on positive feedback from the field about the benefits of reducing sodium intake, we believe that the majority of patients and health care providers will continue to prioritize long term health when evaluating oxybate therapy. Looking at IH, annual revenue from this indication doubled from 2022 to 2023, and we continue to view IH as a source of sustained growth for Zywave. Exiting 2023, there were approximately 2,775 active IH patients on Zywave.

Speaker 1

Given our confidence that the IH indication represents a durable growth opportunity for Zywave, we are continuing to invest in further building this market. We have expanded our sales force, adding field personnel who are focused on IH with the primary directive to increase the depth and breadth of IH prescribers. Turning to Slide 10, we drove another quarter of Epidiolex growth with net product sales approximately $241,000,000 in the 4th quarter, representing a 16% increase compared to the same quarter in 2022. For the full year 2023, Epidiolex revenue was $845,500,000 up 15% year over year, driven by underlying demand and geographic expansion. We remain confident in the long term growth prospects and blockbuster potential of Epidiolex, which is now annualizing at more than $900,000,000 in revenue.

Speaker 1

Key drivers of this demand growth in the U. S. Include positive responses to data on the benefits of Epidiolex beyond seizure control, such as language and communication, cognition, executive function and emotional and social function, as well as increased penetration in the adult patient setting. Further opportunities for growth include continued education to support optimal dosing, focused data generation and geographic expansion beyond the more than 35 countries where Epidiolex is approved, with additional launches and market reimbursement expected in 2024. Moving to oncology, Slide 11 highlights the strong performance of Rylase in 2023, which contributed to our total oncology business exceeding $1,000,000,000 in annual revenue for the first time.

Speaker 1

Rylase delivered net product sales of approximately $102,000,000 for the Q4 2023 and approximately $394,000,000 for the full year, representing 26% 40% year over year increases in those periods, respectively. A number of factors are contributing to continued strong demand for Rylase. Rylase has been almost universally adopted asparaginase based oncology protocols in the U. S. And we continue to see strong adoption of the new Monday, Wednesday, Friday dosing regimen.

Speaker 1

We are also seeing increased usage of Rylase in ALL patients due to some of the benefits of its short acting profile relative to current first line asparaginase therapies, including switches from these first line therapies due to tolerability concerns and side effects. In addition, we have an opportunity for continued growth with increasing use of Rylase in the treatment of adolescents and young adults or the AYA market. Turning to Slide 12 in Zephelka. Net product sales for the 4th quarter increased 3% year over year to $74,000,000 For the full year 2023, net product sales were $289,500,000 up 7% year over year. We have established Sefzelka as the number one treatment for second line small cell lung cancer patients and we continue to hear positive feedback from healthcare providers on its clinical benefit and ease of use and administration for patients and their healthcare practices.

Speaker 1

Since its launch, Zephelka has generated almost $900,000,000 in revenue and is proving to be a highly accretive and well executed corporate development transaction. In addition to the 2nd line setting, there remains an unmet need for patients in earlier lines of therapy. The ongoing Phase III trial in first line small cell lung cancer provides a further opportunity to improve patient lives and outcomes as well as drive future growth. With that, I'll turn it over to Rob for an update on our pipeline and upcoming milestones. Rob?

Speaker 3

Thanks, Renee. 2024 represents an exciting time for us on the R and D front, and we anticipate multiple meaningful catalysts across oncology and neuroscience. On Slide 14, we've provided an overview of the key clinical programs in our diversified pipeline. And I'll highlight several milestones we expect to reach in the near term. Starting with oncology and Zanadatumumab, we anticipate completing our rolling BLA submission for accelerated approval of Zanadatumumab in 2nd line biliary tract cancer or BTC in the first half of this year.

Speaker 3

And I'm excited to report that we recently initiated our first line BTC trial. Additionally, we are targeting late this year to report top line data from the ongoing Phase 3 first line gastroesophageal adenocarcinoma or GEA trial. If positive, we expect this trial would support a registration. I'll speak more to our zanodatumab development plan in just a moment. We're also pleased with the progress of the ZYPSELCA first line trial, which completed enrollment in January of this year.

Speaker 3

Top line progression free survival data for ZYPELCA in combination with Tecentriq in first line extensive stage small cell lung cancer is expected at the end of 2024 or early 2025. If approved, this indication would enable more patients with small cell lung cancer to potentially benefit from longer duration of therapy with SYBZALCA. Turning to neuroscience. We expect top line data from our Phase III trial of Epidiolex in Japan in the second half of twenty twenty four. We also have ongoing trials for suvacaltamide or JZP-three eighty five in both essential tremor and Parkinson's disease tremor, with top line data from the ET trial expected late in the first half of twenty twenty four.

Speaker 3

If trial findings are positive, we believe this trial could serve as part of a pivotal regulatory package. Slide 15 provides more detail on our development plan for Zanadatumab. We have meaningfully progressed Zanaditumab development across indications since bringing it to Jazz last year. And based on the totality of the data, we are highly confident in this molecule as a differentiated therapy for HER2 expressing cancers. I'll note that we are hosting an R and D Day on March 19 that will focus exclusively on danautomab, including perspectives from GEA and breast cancer KOLs.

Speaker 3

Zanadatimab has shown compelling activity across a broad range of HER2 positive tumors and our development plan represents a robust investigation of this molecule in multiple tumor types as outlined on this slide. In addition to our BTC and GEA programs, we see meaningful opportunity for Zanadatimab to improve care for early and late stage breast cancer patients. Slide 16 highlights one of the most critical factors contributing to our enthusiasm around cenadetumab. Specifically, the data generated to date has demonstrated danaadatimab activity as monotherapy in combination with other agents in patients previously treated with other HER2 agents and results in durable responses with encouraging progression free survival and overall survival data. Our development strategy for Zanodatumab starts with BTC, an area of high unmet patient need, where there are currently no approved HER2 therapies.

Speaker 3

We believe coming to market in BTC will enable a fast to market strategy where we can leverage supplemental BLA findings and other indications. DEA is the next potential indication to follow BTC, and we believe prior approval in BTC may accelerate adoption into GEA treatment guidelines and protocols. Following discussions with FDA, we have elected to increase the enrollment target for the GEA trial to improve statistical power for the overall survival endpoint. This will not impact the timeline to potential approval, which is still based on PFS from the original patient enrollment target. We remain committed to rapidly advancing and expanding our development for a molecule that has the potential to transform the current standard of care in multiple HER2 positive cancers.

Speaker 3

Now, I will turn the call over to Bruce for a financial update. Bruce?

Speaker 2

Thanks, Rob. I'll start with our top line results on Slide 18. As a reminder, our full financial results are available in our press release and 10 ks. In the Q4 of 2023, we achieved more than $1,000,000,000 in total revenues. And for full year 2023, we reported more than $3,800,000,000 in total revenues, representing 5% growth over full year 2022.

Speaker 2

We were pleased to deliver growth despite headwinds from the introduction of both branded and AG high sodium oxybate competition with our full year results driven by continued growth in both neuroscience and oncology, including double digit growth from each of our 3 key growth drivers. Turning to Slide 19, our full year 2023 non GAAP adjusted net income was approximately $1,300,000,000 and we reported non GAAP adjusted EPS of $18.29 We continue to generate significant cash from our business, demonstrating the strength and diversity of our global portfolio. We recorded approximately $1,100,000,000 of cash from operations for the full year 2023 and ended the year with $1,600,000,000 in cash on hand. Our strong overall financial position and operating cash flows mean we have significant flexibility to invest in priority commercial and R and D programs as well as corporate development opportunities. We are pleased to share our full year financial guidance for 2024 beginning on Slide 20.

Speaker 2

Our 2024 total revenue guidance range of $4,000,000,000 to $4,200,000,000 represents 7% year over year top line growth at the midpoint. We expect double digit percentage revenue growth of zywaveepidiolex and Rylase combined to drive total revenue growth this year. Our 2024 neuroscience revenue guidance of $2,800,000,000 to $2,950,000,000 reflects the expected growth of Zywave and IH and Epidiolex, offset by the expected decline in Xyrem. I'll note this guidance is inclusive of AG royalties, which we expect to exceed $200,000,000 in 2024. Our 2024 oncology revenue guidance range of $1,120,000,000 to $1,220,000,000 reflects expectations of continued double digit growth for this therapeutic area.

Speaker 2

I'd like to draw your attention to several items on Slide 21. With regard to operating expenses, our SG and A guidance range is $1,170,000,000 to $1,230,000,000 The expected increase in SG and A in 2024 over 2023 will largely be a result of continued investments and our key growth drivers, including ZIWAVE IH initiatives, commercial support for Epidiolex in the U. S. Where we know the market is promotionally sensitive, geographic expansion of Epidiolex outside the U. S.

Speaker 2

And educational efforts for Rylase in AYA. Our R and D guidance range of $800,000,000 to $850,000,000 represents an increase of 5% at the midpoint compared to 2023, driven by planned continued investment in our robust zanidatumab development program. Both SG and A and R and D guidance at the midpoint represent the same percentages of total revenue compared to 2023. On the bottom line, we expect adjusted net income in 2024 to be in line with 2023 with a guidance range of 1.275 dollars to $1,350,000,000 This reflects anticipated investments in our commercial growth drivers and pipeline enabled by top line growth and disciplined and strategic capital allocation. I'll conclude our prepared remarks on Slide 23.

Speaker 2

In 2023, we delivered on our neuroscience, oncology and total revenue guidance. On the commercial side, our 2023 performance was driven by combined double digit growth of key products, XY Wave, Epidiolex and Rylase. On a combined basis, we expect these to grow by double digits again in 2024. This is a very exciting time for Jazz on the R and D front as we continue to advance our pipeline and invest in long term growth with multiple catalysts expected in the near term. As always, we remain focused on operational excellence and strategic capital allocation with corporate development remaining an opportunity for additional growth and diversification.

Speaker 2

In summary, we are poised to deliver top line growth and multiple pipeline catalysts in 2024. And longer term, with our expanding product portfolio, R and D progress and focus on operational excellence, we believe we are well positioned to achieve vision 2025 and deliver further diversification, sustainable growth and enhanced value to patients and shareholders. That concludes our prepared remarks. I would now like to turn the call over to the operator to open the line for Q and A.

Operator

Thank you. We'll take our first question from Jessica Fye with JPMorgan. Your line is open.

Speaker 1

Hey there. Good afternoon. Thanks for taking my question. We're seeing worries about Zywave's position in narcolepsy despite what looks like sleep neuro guidance clearly ahead of consensus. Can you talk about what you're seeing competitively in narcolepsy right now and maybe set expectations for what you think the outlook is for Zaiwave in that setting?

Speaker 1

Thank you.

Speaker 4

Yes. Hi, Jess. Thanks for the question. Renee, maybe I'll turn that one over to you.

Speaker 1

Sure. Yes, happy to comment. Thanks, Jess. So at a high level, as we look at Zywave for 2024, as we noted on the call, we do expect it to be an important growth driver, 1 of 3 as we look at where we expect growth on the top line across the year. We do see Zywave continuing to resonate as a differentiated therapy as the only low sodium oxybate, the number one treatment in narcolepsy and then of course the only drug approved for IH.

Speaker 1

What we're seeing in terms of the market is we are seeing the majority of new toxivate patients starting on Zywave. We do believe it will remain the oxivate of choice. And that said, as we're looking at Q4, as we've said, we do expect some patients to try Lumrize, given there are now many more patients on Zywave than Zyrem naturally, we would expect some impact there. So as we look at exiting the Q4, we had more than 9,500 narcolepsy patients ending the year. Keep in mind also that our patient number is a net number.

Speaker 1

So it reflects the adds from the quarter less any discontinuations that we had. Also in the Q4, we did see an increase in our non revenue bottles as we continue to refine our patient support services program. We are seeing an increase in programs that essentially seek to take advantage of our affordability programs. This increase was seasonal and we don't expect it to continue given how we're refining those programs. And then finally, keep in mind, within the Q4, as we continue to add new patients in both IH and narcolepsy, those patients need to titrate, so the revenue is lower upon starting, meaning that a patient that is starting therapy may not be as valuable upon starting therapy as a patient that's discontinuing.

Speaker 1

And then I'll just say that as we look forward, we do believe that every high sodium patient is a potential Zywave patient. In particular, as we see decreasing commercial coverage for Xyrem, we expect those patients to ship therapy either to authorize generics, which of course we receive a significant royalty on or to fixed dose high sodium branded therapy or importantly to ZY Wave, which will be an additional driver of growth in 2024 for narcolepsy with probably more of our growth coming from idiopathic hypersomnia.

Operator

We will take our next question from Marc Goodman with Leerink Partners. Your line is open.

Speaker 5

Yes. Can you give us a little color just on the oncology portfolio? I mean you have products Defitilio, Vyxeos, Zebzelka, Arwinaze, I'm sorry, Rylai, I still say that Bruce, I apologize. Any color you can give us just on the quarters? I mean, Defitelio and Vyxeos obviously much higher than expected.

Speaker 5

The other two products flattish quarter to quarter. So anything you can provide would be helpful. Thanks.

Speaker 4

Yes. Mark, you're not the only one that occasionally refers to a prior product name. I'll say for some of our products, we do see significant quarter to quarter variability, particularly in the sort of very rare diseases. This has been true of Defitelio for years. So I wouldn't read too much in on the Defitelio, Vyxeos side.

Speaker 4

We've been more focused on the growth in Zepsilka, but particularly on our strong performance with Rylase. And maybe I'll turn it over to Renee to comment a little bit on Rylase.

Speaker 1

Yes. Thanks, Bruce, and thanks for the question, Mark. I would say certainly echoing the variability with respect to Rylase in particular, we did see some seasonality at the end of the Q4 going into the holidays. This is a relatively small market in terms of the rare population here with respect to the use that we see in Rylase. Importantly, we do see Rylase as a growth driver in 2024.

Speaker 1

Just a reminder, due to supply constraints with Erwinaze, we were never really able to fully understand the market potential for that product, but we're continuing to see strong demand overall in the Q4. And we also began a rolling launch in Europe late in the year. That is not an area as we think about Europe that we expect to see a strong contributor to growth in 2024, but we're pleased we were able to get that underway. And then with respect to Zepselka, we've established this as the number one treatment for second line small cell lung cancer and we do see future growth opportunity in first line as we look at reading out that study either late this year or early the next year. We continue to hear positive feedback from HCPs on the clinical benefit, the ease of use, as I mentioned, and seeing additional use there.

Speaker 1

But we do, as Bruce said, have some variability quarter to quarter in that area as well.

Operator

And we will take our next question from Jason Gerberry with Bank of America. Your line is open.

Speaker 6

Hi, good evening. Thanks for taking my question. My question just, how do you foresee with Zanni the frontline GEA differentiating in the PD L1 negative subpopulation if you aren't stratifying patients on the basis of PD L1 status. So is the thought here that as long as that subpopulation doesn't produce a discordant result versus the all comer group, but that should facilitate a broader label than Merck secured with this KEYNOTE-eight eleven regimen. Just kind of wondering how, you can kind of paint that picture?

Speaker 6

Thanks.

Speaker 4

Thanks, Jason, for the question. Rob, you want to weigh in on that?

Speaker 3

Yes. The PD L1 biomarker wouldn't have any predictive value for dana'ditumab or any other HER2 therapies. So we think we can clearly define a benefit in the PD L1 positive or negative subgroups. Of course, we have 2 experimental arms, one where ZANI is combined with standard of care chemo, and we also have an arm where we add PD-one antagonist to that tislelizumab from Beijing. And so we have an opportunity to address both the PD L1 negative group where the standard of care continues to be Herceptin chemo and the PD L1 positive group where PD-1s are shown have been shown to benefit patients.

Speaker 3

And we think in that segment, we have the superior anti HER2 drug. We don't think that there'll be a differential based on which PD-one is used.

Operator

And we will take our next question from Amy Fadia with Needham and Company. Your line is open.

Speaker 7

Hi, good afternoon. Thanks for taking my question. Going back to the oxybate market, can you talk about the market dynamics here, particularly with the entry of LumRise? How has that impacted the total number of patients on oxybate? Do you believe that they are expanding the market or predominantly taking share?

Speaker 7

And how do you envision that evolving in 2024 in your guidance? And maybe just related to that in IH, can you elaborate on where the increased sales force will focus on to drive additional prescribing debt? Thanks.

Speaker 4

Thanks, Ami for those questions. Renee, I'll turn that one over to you.

Speaker 1

Sure. Yes. And thanks. Thank you, Ami. With respect to what we're seeing in narcolepsy, as I'd mentioned, new to oxybate patients today we see the vast majority of those starting on Ziwave.

Speaker 1

Now based on as we look at 2024, for example, we expect to see a continued decline of XiRAM. We've said we expect AG royalties to exceed $200,000,000 and we expect to see Xiwave as an important growth driver. But that growth will likely be greater in IH versus narcolepsy as I'd mentioned before, but the narcolepsy business is very important to us. As we think about what's happening in terms of narcolepsy, given that there are fewer patients that are on Xyrem today versus what are on Ziwave, it would be natural to expect some impact to Ziwave from patients starting on branded fixed dose high sodium Lumarize. We do continue though to see as we look forward this opportunity for some growth within narcolepsy related to some market expansion.

Speaker 1

I think there's very little of that that we're seeing right now. And just given if you're looking at a market opportunity, it would be much easier to go after patients that are already experienced on oxybate. Now with respect to IH, as we look at what's happening with that market, we continue to see an opportunity to continue to educate on the entire condition of IH and the benefit of restorative sleep in terms of the improvement on that overall condition. We are looking at opportunities where we have both experienced oxybate prescribers, but those who are not currently doing a lot of prescribing for IH, as well as broader opportunities to focus on prescribers that are less familiar with oxybate in general, but have a number of patients within their practice on IH.

Speaker 8

And we will take

Operator

our next question from Ash Verma with UBS. Your line is open.

Speaker 9

Hi, thanks for taking my question. So I wanted to just like get your latest thoughts on what you're thinking about bridging to 2025 vision of €5,000,000,000 in sales? Do you think you need business development to get there? And is it possible that you could reconsider the target metrics for 2025 at some point? And then second question, so for Zebzelka on competitive front, there is a drug from Amgen, tarlitumab, or just if you can comment on how do you think the small cell lung cancer space might evolve?

Speaker 4

Thanks. Yes, Ash, thanks for the questions. On the Vision 2025, target for revenue specifically, we had identified that as we came into 2022 as coming about $2,000,000,000 from oxybate. And I'll remind you that we had excellent progress with Zywave in particular in 2023 and we continue to expect additional growth in 2024. Last year, we had over $1,900,000,000 as we move toward the $2,000,000,000 target.

Speaker 4

Epidiolex, we said would be a blockbuster product north of $1,000,000,000 in revenue. We're currently annualizing based on the last quarter at over $900,000,000 and still showing nice growth both in the U. S. And outside the U. S.

Speaker 4

With Epidiolex. So we believe we're solidly on track for that. And we also said our oncology business would contribute north of $1,000,000,000 in 2025. We have Dialect and oncology together contributing 2,500,000,000 dollars and we're very pleased obviously to see our oncology business grow to more than $1,000,000,000 in 2023 and we've again projected nice growth of that business as you can see from our guidance for 2024. So for the organic piece, dollars 4,500,000,000 we feel like we are on track for a vision 2025.

Speaker 4

We of course did include a placeholder of $500,000,000 in 2025 revenues that could come from corporate development transactions done after we announced division 2025. Of course, that could include some revenue contribution from Zanidatumab, where we said we'll finish our rolling BLA submission in the first half of this year, and we're projecting that launch come in 2025 or sooner. We're not suggesting that that would make up all of that $500,000,000 in 2025, but we are in strong financial position with our cash and our cash flow to be active on the corporate development side and we continue to review targets that would make interesting additions to our business. I'll point out we're not going to do a deal just to do a deal. We're going to do a deal if it's a good use of our capital.

Speaker 4

It furthers our strategy, adds an additional growth driver and provides sustainability over not just 2025, but as we look through the period 2025 to 2,030. So long answer, Ash, to a short question, but we're making excellent progress toward vision 2025. And on the Zepsilica side, maybe Rob, I'll turn

Speaker 2

that one over to you.

Speaker 3

Happy to, Bruce. As you know, tarlodumab is a very different mechanism of action than Xybcelka. The data that will support that have supported a BLA are in the 3rd line versus Ypsilka in the 2nd line. And the safety profile for tarlonimab is really quite different with a high risk of CRS and serious CRS even in including neurological effects. And that safety profile may well be a significant challenge, especially for community practitioners where many small cell lung cancer patients are treated.

Speaker 3

In contrast, FERC has a very favorable safety profile, can be easily given as an infusion once every 3 weeks. And that really makes it an ideal candidate for add on therapy in the frontline setting. And as you know, in partner with Genentech, we are running a frontline trial in small cell lung cancer. We expect top line PFS results as early as the end of this year, and that will allow greater proportion of patients to receive therapy for a longer time.

Speaker 1

And just to build on that further. So as we look at that opportunity in first line, we also given the tolerability profile, the patient experience, the clinical activity. These patients that are coming in with second line small cell lung cancer generally have quite a poor health prognosis. So they've already relapsed at this point. And so having a drug that's very easy to use is quite important in the treatment decision.

Operator

And we will take our next question from Joseph Tommi with TD Cowen. Your line is open.

Speaker 4

Hi there. Good evening.

Speaker 10

Congrats on the progress and thank you for taking my question. Maybe just one on zanadimab. How should we think about continued investment in the program overall? I know you outlined the breast cancer opportunity in other HER2 expressing cancers. I guess what sort of the decision point to make that additional investment start additional studies either in breast cancer or some of these other cancers?

Speaker 10

Is it the first kind of approval in BTC? Is it if it works in GEA? Or are you looking more at the landscape overall in competition? How should we think about the appetite to expand that? Thank you.

Speaker 4

Yes. I'll start and then Renee or Rob, if you want to add anything in, you certainly can. While we don't give R and D guidance by program, you saw our R and D guidance for the full year represents about the same percentage of total revenues as we reported for 2023. With zanidatumab having contributed a lot to the growth in R and D 2023 over 2022, we have a little bit more of an apples to apples comparison between 2023 and 2024. I will say our guidance does assume activity in breast as well as BTC and GEA and will certainly at our R and D Day in March be explaining a little bit more about our specific plans.

Speaker 4

But, Rob, let me know if you want to say more now.

Speaker 3

Yes. Only that, of course, we're already working in areas outside of BTC and GEA. We've published data in the metastatic breast cancer setting both HER2 positive and the combined HER2 ER positive patients early in metastatic setting. So we already have data. And as Bruce mentioned, we are planning for additional work in breast cancer even now.

Operator

And we will take our next question from Gregory Renzo with RBC Capital Markets. Your line is open.

Speaker 11

Hey, good afternoon, good evening, Capers and team. Congrats on the progress and

Speaker 4

thanks

Speaker 11

for taking my question. Maybe Bruce, just adding on to some of the color that you provided around Vision 25 and that $500,000,000 potentially through corporate development. Just curious if you could comment a bit on where you see valuations for some of the areas in which you're looking externally, certainly 2023, as you've noted, maybe put Jazz based on where the markets were in a position of strength. I'm just curious how you see 2024 to date for competition, for attractiveness of assets that are in Jazz's power alley? Thanks so much.

Speaker 4

Greg, thanks for the question. We have quite a bit of experience on the corp dev side having done a number of these transactions over the years and feel like there is a great set of opportunities out there across neuroscience and oncology as well as some rare disease spaces that would build on capabilities we already have in house based on a lot of our activities over recent years. Being active in all of those spaces, looking at on market and near market products, including some in late stage development, I think gives us the ability to find things at valuations that work for us. There can be pockets of areas where it seems like everyone's looking at the same time valuations maybe a little higher or in a good turn. If that's true, that's why we look at other areas as well.

Speaker 4

So with our team, with our strong financial position, we're confident we'll continue to find opportunities to put capital to good work to drive that growth and sustainable growth over a longer period of time.

Speaker 8

And we will take

Operator

our next question from Annabel Samimy with Stifel. Your line is open.

Speaker 8

Hi. Thanks for taking my question. On XAN, I know that you're still in the rolling BLA process, but can you talk about your launch plans there? How you might be preparing for it in terms of sales? What type of investment you need to make in the launch, the infrastructure to appropriately target GI cancers versus lung cancers?

Speaker 8

And could that potentially impact, say, Zepselka? And then I guess sort of related on the operating margin, Vision 2025, I guess, was supposed to be 5 points over where the guidance was set back in 2022. I think you're still at 43% and that would have been 48%. So are you backing off of that operating margin guidance given the number of investments you have to make here? Or just if you can give a little color there, that would be great.

Speaker 8

Thanks.

Speaker 4

Yes. Annabel, maybe I'll take the second part of your question first and then we'll come back to zanidatumumab commercial launch thinking. When we set that target, it was coming off 43% margin back in 2021. I'll point out we essentially achieved that increase in margin as we moved through 2022. That's given us great flexibility to make the kinds of investments we wanted to make in the R and D portfolio and behind our key growth drivers on the commercial side.

Speaker 4

So we're glad to be making those investments today. We obviously haven't given guidance for 2025 specifically yet. I will point out, as we've pointed out before, that whether or not we do a corporate development transaction and spread our expenses over a greater revenue base does impact our margins. So we built that into our thinking as well. But for now, we think the investments we're making are investments that will lead to high return for our shareholders.

Speaker 4

Renee, you want to talk about zanidatamab?

Speaker 1

Sure. Yeah. Thanks for the question. So with respect to how we're thinking about BTC, we believe we have the ability to really effectively cover our BTC launch, which could happen as early as later this year. We'll be ready certainly, but we're looking at more than likely 2025.

Speaker 1

So the way we're thinking about the launch is we should be able to leverage our current field force that is out in the field right now with Sapsilka with a relatively small augment to that field force. The key is to enter the market with BTC to help HCPs get important experience with SaniDatumap. We do expect to have our GEA data as early as the end of this year. That's what we're targeting. And so by being in a position where we have our HCPs getting experience with XANI, it's a more seamless transition when you're thinking about GEA.

Speaker 1

Also if we're looking at an SBLA process for GEA, that's of course a bit faster as well. So we think it's a relatively small expansion to the footprint in the U. S. And we're also looking at Xanny as a global brand, an important global brand for us. So after the U.

Speaker 1

S. We're also looking at Europe as well as Japan. And while the BTC opportunity holistically from an epidemiology perspective is smaller, it's a high unmet need in terms of the severity of the cancer. And so we're looking at a build strategy start with BTC where we have around 12,000 patients worldwide build into GEA with 63,000 And when I say worldwide, I mean the U. S, Europe and Japanese markets.

Speaker 1

And then as we expand into breast, we're looking at a much larger population of more than 150,000 patients. So that's how we're looking at the broader opportunity.

Operator

And we will take our next question from David Amsellem with Piper Sandler. Your line is open.

Speaker 4

Hey, thanks. Can you talk a little more about Epidiolex and what drove the performance? Is are you seeing double digit volume growth both U. S. And ex U.

Speaker 4

S. And was there any stocking benefit that we should be aware of? Thank you. Thanks for the question, David. Renee, maybe I'll turn that one over to you.

Speaker 1

Sure. Yes, happy to comment. So as we look at the DIALEX, as we've said in the past, we tend to see a more gradual buildup over the second half of the year and then that works off over the first half of the year. We saw very small amount of that in the Q4 in terms of build up. But we are seeing continuing demand growth and we're seeing that across both the U.

Speaker 1

S. As well as in Europe. We've said in the past what continues to resonate with physicians, providers, patients is really the understanding of some of the beyond seizure benefits as well as the synergistic effect we're seeing with clobazam. We see continued opportunity in the adult segment. That's an area we're starting to focus a bit more on and that we expect to be a driver of growth in 2024.

Speaker 1

And then more broadly, as we look at how Epidiolex is viewed in the market as the number one branded treatment, it continues to be seen as a very well characterized and tolerated drug, which means that lends itself well to polypharmacy. That's the norm in this area. And the data that we continue to generate both, as I just described in terms of with clobazam and the data beyond seizures and just further understanding of these effects that you're seeing is creating greater demand from our physicians stating they intend to use it earlier in their process of this poly pharmacy with patients. We are seeing growth outside the U. S.

Speaker 1

As well as I'd mentioned. So we're continuing to both launch in new geographies and then add indications within existing geographies. And so that growth is proceeding nicely as well.

Operator

And we will take our next question from Joon Lee with Truist Securities. Your line is open.

Speaker 12

Thanks for the update and for taking our questions. When you do report top line data from sumacaltenamide in essential tremor, will you have a go no decision gono go decision when you report to top line? Or is that something that you still have to consult with the FDA in an end of Phase 2 meeting before being able to comment on a go, no go decision? And is the advancement into Parkinson's disease dependent on the outcome of ET or are they independent events? And just quickly, anything you can share on the latest on the Oraxol program?

Speaker 12

Thank you.

Speaker 4

So the first part of the question was around essential tremor. And I would say, in general, our practice has been to share top line data on a timely basis. Whether we comment precisely at that time on next steps remains to be seen and remains to be remains dependent on the data. But in general, our view is we know what we need to move this program forward. So I'm not sure that barring a surprise in the data that would involve a different regulatory

Speaker 2

interaction. Rob, anything else you want to

Speaker 4

add on HC or on Orexin?

Speaker 3

I would just say that with regard to ET, I agree with you that we'll see the data and we're not expecting to have to talk to FDA before providing some guidance on that. It certainly is positioned as a pivotal trial. We're very excited about it given the high unmet need. There hasn't been an approved drug in 50 years and what's available there is pretty poor. We think we have a differentiated mechanism of action and a best in class calcium channel modulator.

Speaker 3

Certainly, this trial was built to be part of a pivotal program. So I think it will be quite informative when we do see the data. I don't think Parkinson's disease tremor is a direct read through, but certainly strong data in essential tremor would give us more confidence in this target overall. And then finally, on the question of Orexin, no updates there. We're on pause while we're examining the safety findings that we previously characterized.

Operator

And we will take our next question from Gary Nachman with Raymond James. Your line is open.

Speaker 4

Hi, good afternoon. So on Sani, just what's the timeline for expanding further into breast cancer? Will you be doing that in parallel with and GEA? And then regarding increasing the size of the GEA trial, just describe what you hope to see from that interim OS data? And next year, is it possible that GEA could contribute to the sales of XANNI and not just BTC?

Speaker 4

Thank you. Rob, I'm going to turn this one over to you.

Speaker 3

Yes. So similar to the answer I gave previously, we have been working in breast cancer already, both in the metastatic setting for HER2 positive cancer and then we published recently on HER2 positive ER positive breast cancer at San Antonio last year. We published on early stage disease. So we have been working in breast cancer and publishing on those data. And we are progressing further development plans in those areas.

Speaker 3

It's not dependent on any other readout. With regard to the changes to the GEA study, again, we made those changes to ensure better power for the overall final overall survival endpoint. We plan to read out the progression free survival based on the original sample size, so it tends to have no impact on the overall timeline. And we know from health authority interactions that in this setting PFS is adequate to support approval. It's usual and typical to do an interim analysis, albeit early on OS at the time that you're looking at PFS.

Speaker 3

And generally, health authorities just want to be sure that something funky is not happening that you're not seeing somehow a detriment in the OS. But there's not an expectation that OS on that first interim would be well powered. Then of course, we have the 2nd interim analysis, which is occurring around the time that it would have on the original trial, which is why we believe we sort of have our cake and eat it too with this change. And then on the MatureOS data, we'd have more power.

Speaker 1

And then with respect to Yes.

Speaker 3

I mean, in terms of sorry, I didn't get to the didn't address the question on revenue in 2025. There is a scenario where we are given what we've shared around BTC that we are on the market for BTC. And as we read out the data for GEA, we certainly have a faster path as a supplemental in the U. S. To get an update to the label, but we certainly will also publish and seek compendia listing even while we are progressing the supplemental BLA.

Operator

We will take our next question from Akash Tewari with Jefferies. Your line is open.

Speaker 13

Hi, this is Ivy on for Akash. Thanks for taking our question. Just a quick one on Xyney and GAA. So given the mechanism similarity between Herceptin, Perjeta combo and Xyney, Why do you think their Phase 3 GA trial, Jacob, failed? It doesn't seem to be like HER2 expression related, given the treatment arm enrolled roughly similar HER2-three population compared to the comparator arm, which is Herceptin plus chemo.

Speaker 13

So is there anything you are doing differently in your trial? Thanks.

Speaker 4

Rob, do you want to take that?

Speaker 3

Yes. I have it too, Bruce. So first of all, while the epitopes on Zanadatimab do correspond to the same epitopes that Herceptin and Perjeta independently bind, The reasons onadatumab is differentiated is that when they occur, when they're positioned on the same antibody, what you get is binding of the 2 Fab fragments of the antibody on different receptors. And it causes receptor clustering, which enhances interference signaling, whether that be through HER2 or interference of dimerization with HER3 and therefore interference of signaling with HER3, internalization, and marking the cells for immune destruction. A lot of this experimental data was published in Nature Communications and includes some really nice data showing this clustering effect that occurs

Speaker 10

with the

Speaker 3

bipyratopic antibody and showing that it induces complement dependent cytotoxicity, which is unique amongst any HER2 antibodies. And also some experimental data comparing head to head to just combining those 2 antibodies separately. So we think we actually have a differentiated drug that will be more effective in giving the combination. And our clinical data, by the way, support that. So we have activity in patients who have progressed on the combination of Herceptin and Perjeta with breast cancer.

Speaker 3

So I think our preclinical data show the differentiated mechanism and the clinical data are showing better results, whether it be in breast cancer or also in BTC, where we seem to have better results than when you give Herceptin Perjeta to BTC patients.

Operator

And we will take our next question from Charles Duncan with Cantor Fitzgerald. Your line is open.

Speaker 13

Hi. This is Assia on for Charles. We have a question on Epidiolex. So given the Phase 3 readout in the second half of this year, can you talk a little bit about the addressable market and opportunity in Japan compared to the market compared to the opportunity in the U. S?

Speaker 13

And also, you did mention additional market launches this year. So I was wondering if you can provide a bit more color on this?

Speaker 1

Thank you. Yes. Renee, let

Speaker 4

me turn that one over to you.

Speaker 1

Sure. Yes, I'm happy to jump in there. So for Japan, we're excited to be able to have made the progress that we have in that geography. There's about 20,000 patients across 3 different indications that we think provide quite an important opportunity. And Japan obviously is the 2nd largest pharmaceutical market in the world.

Speaker 1

We have now the opportunity not only with Epidiolex but also Zandidetimab to be able to have meaningful opportunities in that market. So we do expect the top line results in the second half of this year and we're pleased also with the progress we've made to be able to see changes to the Cannabis Control Act underway, which will enable that eventual launch. And then in terms of outside the U. S, as we think about the progress that we're making there. We're already approved in more than 35 different countries.

Speaker 1

We do have some additional launches and reimbursements anticipated through the end of 2024. And I would think of that as gradual updates as we go. We are already approved and reimbursed in the 5 main large markets in Europe. So what we've been doing over the course of 2023 2024 is really focused on ensuring we have the full indication set available in each of the countries. We're continuing to be able to execute partnership agreements to ensure that either if we're not going direct, we're making the product available through our partners and we'll expect that to continue over the course of 2024.

Speaker 1

And given we're now in a place where we're annualizing at more than 900,000,000 dollars we see the product as being very much on track for blockbuster status.

Operator

And we will take our next question from Jeff Hung with Morgan Stanley. Your line is open.

Speaker 6

Hi. This is Michael Riad on for Jeff Hung. Thank you for taking our question. On the high sodium authorized generics, what evidence generation is needed to support the long term health messaging and drive patients like towards the switch to low sodium? Or do you

Speaker 4

think that the majority of

Speaker 6

the narcolepsy and IH community are more or less aligned with the benefits given the need for lifelong treatment? Thank you.

Speaker 4

Yes. I would say the evidence surrounding the impact of SODIA on cardiovascular health is pretty incontrovertible. Certainly underlied the original orphan drug exclusivity decision by FDA determining that Zywave was clinically superior to Xyrem on the basis of that lower sodium. The same thing could be said for Lumeriz, which has the same sodium level as Xyrem. It doesn't mean there aren't opportunities to bring out more data as we have already, including with our presentation at the neurology meeting last year that within a period of 180 days of starting sodium oxybate therapy, we saw patients have a significantly increased either diagnosis of hypertension or beginning antihypertensive med.

Speaker 4

So even in a short period of time, you see that impact on people, even if they aren't already diagnosed as being hypertensive patients, which is again why that original determination was that, Zywave will be a safer product in all narcolepsy patients who are known to be at high cardiovascular risk to begin with.

Operator

And we will take our next question from Joel Beatty with Baird. Your line is open.

Speaker 4

Hi, thanks for taking the questions. For zenidetimab, how much of the $2,000,000,000 in peak sales potential projection comes from breast cancer? And are you able to give a sense of when we might see data in that setting from the iSPY-two and MD Anderson collaboration trials? I'll take the first part of that and then Rob hand the data part of it over to you. We have not provided a breakdown of the opportunity set for zanidamab, which we believe is extensive.

Speaker 4

And certainly in our slides, you can see that while we have made the most commentary thus far on BTC and GEA and breast cancer, it certainly has potential beyond those indications as well, which is why we say north of $2,000,000,000 we haven't fully quantified how big the product could be as we determine where else to take it. We've got our near term priorities worked out and looking forward to sharing a little more information at our R and D Day. But on timing of data, Rob, maybe I'll turn that one over to you.

Speaker 3

Yes. For the MD Anderson neoadjuvant study, some data were already published. You may be aware of that, December at San Antonio. That trial is ongoing and I would expect some updates. They haven't indicated exactly when the updates will be published.

Speaker 3

On iSPY, which is a little bit late,

Speaker 4

has started a

Speaker 3

little bit after that trial, really depends on the enrollment rate and the results and when that might graduate from that phase. And so we don't have any specifics at this point. But we are pleased that the trials are ongoing and we're excited to see how that may inform next steps in that early stage space where we think XANNI is particularly well positioned to provide a better tolerated option for women with curative breast cancer.

Operator

And ladies and gentlemen, we have no further questions at this time. I will now turn the call back to Mr. Bruce Kozab for closing remarks.

Speaker 4

Thank you, operator. I'd like to close today's call by recognizing our Jazz colleagues for their efforts and thank our partners and shareholders for their continued confidence and support. Thank you all for joining us today.

Operator

And ladies and gentlemen, this concludes today's call and we thank you for your participation. You may now

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Earnings Conference Call
Jazz Pharmaceuticals Q4 2023
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