Q4 2023 Jazz Pharmaceuticals plc Earnings Call

February 28, 2024

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 Q4 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 speaker's remarks, there will be a question and answer session. If you would like to ask a question during that time, simply press the star key followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one a second time. Thank you. And I will now turn the conference over to Andrea Flynn, Head of Investor Relations. Ms. Flynn, you may begin.

Operator: Good afternoon, ladies and gentlemen. My name is Abby and I'll be your conference operator today. At this time, I would like to welcome everyone to the Jazz Pharmaceuticals Fourth 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 speaker's remakrs, there will be a question and answer session. If you'd like to ask a question during that time, simply press the star key followed by the number 1 on your telephone keypad. If you would like to withdrawl your question, press *1 a second time. Thank you. And I will now turn the conference over to Andrea Flynn, Head of Investor Relations. Ms. Flynn, you may begin.

Abby: At this time I would like to welcome everyone to the jazz Pharmaceuticals fourth quarter 2023 earnings Conference call.

Abby: Today's conference is being recorded in all lines have been placed on mute to prevent any background noise.

Abby: After the Speakers' remarks, there will be a question and answer session. If you would like to ask a question during that time simply press. The star key followed by the number one on your telephone keypad.

Abby: If you would like to withdraw your question Press Star one a second time.

Abby: Thank you and I will now turn the conference over to Andrea Flynn head of Investor Relations Ms. Lynn you may begin.

Andrea Flynn: Thank you, operator, and good afternoon, everyone.

Andrea Flynn: Thank you, operator, and good afternoon, everyone. Today, Jazz Pharmaceuticals reported its fourth quarter and fully year 2023 financial results. The slide presentation accompanying this webcast is available on the Investors section of our website. Investors may also refer to the press release we issued earlier today, which is also posted to our website. On the call today are Bruce Cozadd, Chairman and Chief Executive Officer; Renee Gala, President and Chief Operating Officer; and Rob Iannone, 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.

Bruce Cozadd: Today, Jazz Pharmaceuticals reported its Q4 and full year 2023 financial results. The slide presentation accompanying this webcast is available on the investors section of our website. Investors may also refer to the press release we issued earlier today, which is also posted to our website. On the call today are Bruce Cozadd, Chairman and Chief Executive Officer; Renée Galá, President and Chief Operating Officer; and Rob Iannone, 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.

Andrea Flynn: Today, Jazz Pharmaceuticals reported its Q4 and full year 2023 financial results. The slide presentation accompanying this webcast is available on the investors section of our website. Investors may also refer to the press release we issued earlier today, which is also posted to our website. On the call today are Bruce Cozadd, Chairman and Chief Executive Officer; Renée Galá, President and Chief Operating Officer; and Rob Iannone, 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.

Andrea N. Flynn: On the call today are Bruce <unk>, Chairman and Chief Executive Officer, Renee Gala, President and Chief operating Officer, and Rob You know executive Vice President and global head of R&D.

Andrea N. Flynn: On slide two I'd like to remind you that today's webcast includes forward looking statements such as those related to our future financial and operating result growth potential and anticipate a 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.

Andrea Flynn: 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.

Andrea N. Flynn: Forward looking statements.

Bruce Cozadd: 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 file links, 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. 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. 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.

Andrea Flynn: 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 file links, 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. 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.

Andrea Flynn: 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. We undertake no duty or obligation to update our forward-looking statements. As read on slide 3, we'll 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.

Andrea N. Flynn: We undertake no duty or obligation to update our forward looking statement.

Andrea N. Flynn: As noted on slide three 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.

Bruce Cozadd: 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.

Bruce C. Cozadd: Thanks, Andrea. Good afternoon, everyone. Thank you for joining us today to discuss our fourth quarter and full year 2023 results, and our excitement about 2024. I'll start on slide 5. 2023 was a highly productive year for Jazz. Thanks to the passion and innovation of our talented employees around the world, we helped more patients generate more than $3.8 billion 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 Philip Johnson is joining Jazz as our Chief Financial Officer effective March 1st. Phil comes to Jazz from Eli Lilly, where over the course of almost three 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.

Bruce C. Cozadd: Thanks, Andrea. Good afternoon, everyone. Thank you for joining us today to discuss our fourth quarter and full year 2023 results, and our excitement about 2024.

Bruce Cozadd: I'll start on slide 5. 2023 was a highly productive year for Jazz. Thanks to the passion and innovation of our talented employees around the world, we helped more patients, generated more than $3.8 billion 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 1 March. Phil comes to Jazz from Eli Lilly, where over the course of almost three decades, he led several finance functions and was most recently group vice president of finance and treasurer.

Bruce: I'll start on slide five.

Bruce C. Cozadd: I'll start on slide 5. 2023 was a highly productive year for Jazz. Thanks to the passion and innovation of our talented employees around the world, we helped more patients generate more than $3.8 billion 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 Philip Johnson is joining Jazz as our Chief Financial Officer effective March 1st. Phil comes to Jazz from Eli Lilly, where over the course of almost three 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.

Bruce: 2023 was a highly productive year for Jos thanks to the passion and innovation of our talented employees around the world. We helped more patients generated more than $3 $8 billion in revenues and advanced multiple pipeline programs.

Bruce: We believe these accomplishments position us well for success in 2024, as we focus on commercial execution and accelerating topline growth delivering on key pipeline catalysts and remaining active in assessing corporate development opportunities to drive growth and value creation.

Bruce C. Cozadd: Before we move on, I want to highlight our announcement from last week that Philip Johnson is joining Jazz as our Chief Financial Officer effective March 1st. Phil comes to Jazz from Eli Lilly, where over the course of almost three 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 Change: Before we move on I want to highlight our announcement from last week.

Speaker Change: Phil Johnson is joining jazz as our Chief Financial Officer effective March one.

Speaker Change: Bill comes to jobs from Eli Lilly, where over the course of almost three decades. He led several finance functions and was most recently group Vice President of Finance and Treasurer.

Bruce Cozadd: As we move into 2024, we are excited to add Phil's industry experience, leadership, and strategic approach to our executive team. Turning to slide six, our performance in 2023 is reflective of the strong execution that has transformed our business over the past several years. Highlighting a few commercial accomplishments in 2023, combined revenue from our key growth drivers, Xywav, Epidiolex, and Rylaze, increased 27% year over year. We drove more than $1.9 billion 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. Epidiolex is now annualizing at more than $900 million and on track to deliver on its blockbuster potential.

Speaker Change: As we move into 2024, we are excited to add fills industry experienced leadership and strategic approach to our executive team.

Bruce C. Cozadd: 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, XYWAV, EPIDIOLEX, and RYLAZE increased 27% year-over-year. We drove more than $1.9 billion 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. EPIDIOLEX is now annualizing at more than $900 million and on track to deliver on its blockbuster potential. Our oncology therapeutic area surpassed $1 billion in revenue for the year, with RYLAZE leading the way with 40% year-over-year. Moving to our R&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've used any data map as our most derisk asset with more than a $2 billion peak potential. On the operational front, our discipline capital allocation provides the financial strength to invest in our continued growth and diversification while generating healthy operating cash flow and margins. We have a strong track record of successful corporate development and remain focused on evaluating additional transactions.

Speaker Change: Highlighting a few commercial accomplishments in 2023 combined revenue from our key growth drivers sideways dialects in railways increased 27% year over year.

Speaker Change: We drove more than $1.9 billion in revenue from our sleep therapeutic area reinforcing our confidence in its durability.

<unk> continues to grow reflecting strong underlying demand and the execution by our commercial team.

<unk> is now annualizing at more than $900 million.

Speaker Change: And on track to deliver on its blockbuster potential.

Bruce Cozadd: Our oncology therapeutic area surpassed $1 billion in revenue for the year, with Rylaze leading the way with 40% year-over-year growth. Moving to our R&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 Zanidatamab as our most de-risked asset with more than a $2 billion 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. 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.

Speaker Change: Our oncology therapeutic area surpassed $1 billion in revenue for the year with Riley is leading the way with 40% year over year growth.

Speaker Change: Moving to our R&D and pipeline efforts, we have multiple near term late stage catalysts targeting significant market opportunities.

Speaker Change: Given the strength of clinical data to date across multiple indications. We've used any data map as are most derisked asset with more than a $2 billion peak potential.

Speaker Change: 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 Change: We have a strong track record of successful corporate development and remain focused on evaluating additional transactions.

Bruce C. Cozadd: 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&D have expanded our capabilities and the breadth and depth of our pipeline. And on operational excellence, discipline 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. I'll now turn the call over to Renee to review our commercial performance, after which Rob will share an update on our R&D progress. I'll provide a financial overview, and then we'll open the call to Q&A. Renee?

Bruce Cozadd: 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&D have expanded our capabilities and the breadth and depth of our pipeline. 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. I'll now turn the call over to Renée to review our commercial performance, after which Rob will share an update on our R&D progress. I'll provide a financial overview, and then we'll open the call to Q&A. Renée? Thanks, Bruce. We had a strong Q4, generating quarterly revenue of more than $1 billion for the first time.

Speaker Change: On the commercial side, we've executed successful launches with leading therapies in narcolepsy in epilepsy, and a growing oncology portfolio.

Speaker Change: Our investments in R&D have expanded our capabilities and the breadth and depth of our pipeline and.

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

Renée Galá: Thanks, Bruce. We had a strong Q4, generating quarterly revenue of more than $1 billion for the first time.

Renee Gala: Thanks, Bruce. We had a strong fourth quarter, generating quarterly revenue of more than a $1 billion for the first time. This capped off a successful 2023, in which we achieved year-over-year double-digit growth across each of our key products, XYWAV, EPIDIOLEX, and RYLAZE. I'll start on slide 9 with our sleep therapeutic area. Total revenue from sleep, which includes XYWAV and XYREM sales, plus royalties from high-sodium oxybate authorized generics, or AGs, was $483 million in the fourth quarter of 2023, and exceeded $1.9 billion for the full year. We believe we are well positioned to achieve our Vision 2025 goal of $2 billion in sleep revenue. XYWAV revenue was $337 million for the fourth quarter of 2023, and approximately $1.3 billion 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 oxybate in 2023. We remain confident in the durability of our sleep therapeutic area, and XYWAV in particular as the only low-sodium oxybate and the only therapy approved to treat idiopathic hypersomnia, or IH, we expect XYWAV to remain the oxybate choice, including the number-one treatment for narcolepsy.

Bruce Cozadd: This capped off a successful 2023 in which we achieved year-over-year double-digit growth across each of our key products, Xywav, Epidiolex, and Rylaze. I'll start on slide 9 with our sleep therapeutic area. Total revenue from sleep, which includes Xywav and Xyrem net sales, plus royalties from high-sodium oxybate authorized generics, or AGs, was $483 million in the fourth quarter of 2023 and exceeded $1.9 billion for the full year. We believe we are well positioned to achieve our vision 2025 goal of $2 billion in sleep revenue. Xywav revenue was $337 million for the fourth quarter of 2023 and approximately $1.3 billion for the full year 2023, which represented year-over-year annual growth of 33%.

Renée Galá: This capped off a successful 2023 in which we achieved year-over-year double-digit growth across each of our key products, Xywav, Epidiolex, and Rylaze. I'll start on slide 9 with our sleep therapeutic area. Total revenue from sleep, which includes Xywav and Xyrem net sales, plus royalties from high-sodium oxybate authorized generics, or AGs, was $483 million in the fourth quarter of 2023 and exceeded $1.9 billion for the full year. We believe we are well positioned to achieve our vision 2025 goal of $2 billion in sleep revenue. Xywav revenue was $337 million for the fourth quarter of 2023 and approximately $1.3 billion for the full year 2023, which represented year-over-year annual growth of 33%.

Renee: This capped off a successful 2023 in which we achieved year over year double digit growth across each of our key products XI wave at the dialects and Riley I'll start on slide nine with our sleep therapeutic area.

Renee Gala: I'll start on slide 9 with our sleep therapeutic area. Total revenue from sleep, which includes XYWAV and XYREM sales, plus royalties from high-sodium oxybate authorized generics, or AGs, was $483 million in the fourth quarter of 2023, and exceeded $1.9 billion for the full year. We believe we are well positioned to achieve our Vision 2025 goal of $2 billion in sleep revenue. XYWAV revenue was $337 million for the fourth quarter of 2023, and approximately $1.3 billion 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 oxybate in 2023. We remain confident in the durability of our sleep therapeutic area, and XYWAV in particular as the only low-sodium oxybate and the only therapy approved to treat idiopathic hypersomnia, or IH, we expect XYWAV to remain the oxybate choice, including the number-one treatment for narcolepsy.

Renee: Total revenue from fleet, which includes Xyrem Xyrem net sales plus royalties from high sodium oxidate authorized generics or AG with $483 million in the fourth quarter of 2023 and exceeded $1 $9 billion for the full year. We believe we are well positioned.

Session to achieve our vision 2025 goal of $2 billion and sweep revenue.

Renee: <unk> revenue was $337 million for the fourth quarter of 2023, and approximately $1 $3 billion for the full year 2023, which represented year over year annual growth of 33%.

Bruce Cozadd: 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 Xywav in particular. As the only low-sodium oxybate and the only therapy approved to treat idiopathic hypersomnia, or IH, we expect Xywav to remain the oxybate of choice, including the number one treatment for narcolepsy. Exiting 2023, there were approximately 9,525 narcolepsy patients taking Xywav. 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 healthcare providers will continue to prioritize long-term health when evaluating oxybate therapy.

Renée Galá: 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 Xywav in particular. As the only low-sodium oxybate and the only therapy approved to treat idiopathic hypersomnia, or IH, we expect Xywav to remain the oxybate of choice, including the number one treatment for narcolepsy. Exiting 2023, there were approximately 9,525 narcolepsy patients taking Xywav. 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 healthcare providers will continue to prioritize long-term health when evaluating oxybate therapy.

Renee: We have increasing visibility into oxidate market dynamics since the entry of branded and AG high sodium ox abates in 2023.

Renee: We remain confident in the durability of our sleep therapeutic area and sideways in particular.

Renee: The only low sodium ox abate and the only therapy approved to treat idiopathic hypersomnia or IH, we expect <unk> to remain the oxidative choice, including the number one treatment for narcolepsy exiting 2023, there were approximately 9525.

The only low sodium ox abate and the only therapy approved to treat idiopathic hypersomnia or IH, we expect <unk> to remain the oxidative choice, including the number one treatment for narcolepsy

Renee Gala: Exiting 2023, there were approximately 9,525 narcolepsy patients taking XYWAV. 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 healthcare 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 XYWAV. Exiting 2023, there were approximately 2,775 active IH patients on XYWAV. Given our confidence that the IH indication represents a durable growth opportunity for XYWAV, we are continuing to invest in further building this market. We have expanded our salesforce, adding field personnel who are focused on IH with the primary directive to increase the depth and breadth of IH prescribers.

Renee: C patients taking highway.

Renee: Our focus is on educating patients and prescribers around the lifelong burden of high sodium intake for narcolepsy patients.

Renee: 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 oxalate therapy.

Bruce Cozadd: 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 Xywav. Exiting 2023, there were approximately 2,775 active IH patients on Xywav. Given our confidence that the IH indication represents a durable growth opportunity for Xywav, 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 of approximately $241 million in Q4, representing a 16% increase compared to the same quarter in 2022.

Renée Galá: 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 Xywav. Exiting 2023, there were approximately 2,775 active IH patients on Xywav. Given our confidence that the IH indication represents a durable growth opportunity for Xywav, 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 of approximately $241 million in Q4, representing a 16% increase compared to the same quarter in 2022.

Renee: Looking at I H annual revenue from this indication doubled from 2022 to 2023, and we continue to view IH as a source of sustained growth for sideways.

Renee Gala: Exiting 2023, there were approximately 2775 active IH patients on <unk>.

Renee: Given our confidence that the IH indication represents a durable growth opportunity for <unk>, we are continuing to invest in further building. This market. We have expanded our sales force, adding field personnel, who are focused on I H with the primary directive to increase the depth and breadth of IH prescribe.

Renee Gala: Turning to slide 10, we drove another quarter of EPIDIOLEX growth with net product sales of approximately $241 million in the fourth quarter, representing a 16% increase compared to the same quarter in 2022. For the full year 2023, EPIDIOLEX revenue was $845.5 million, 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 million in revenue. 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.

Renee: Turning to slide 10, we drove another quarter of that the dialects growth with net product sales of approximately $241 million in the fourth quarter, representing a 16% increase compared to the same quarter in 2022.

Bruce Cozadd: For the full year 2023, Epidiolex revenue was $845.5 million, 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 million in revenue. Key drivers of this demand growth in the US 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.

Renée Galá: For the full year 2023, Epidiolex revenue was $845.5 million, 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 million in revenue. Key drivers of this demand growth in the US 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.

Renee: For the full year 2023 at the dialects revenue was $845 $5 million up 15% year over year, driven by underlying demand and geographic expansion. We remain confident in the long term growth prospects and blockbuster potential about the dialects, which has now annualized.

Renee: Rising up more than $900 million in revenue.

Renee: Key drivers of this demand growth in the U S include positive responses to data on the benefits without the dialects 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.

Renee Gala: 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 RYLAZE in 2023, which contributed to our total oncology business exceeding a $1 billion in annual revenue for the first time. RYLAZE delivered net product sales of approximately $102 million for the fourth quarter of 2023 and approximately $394 million for the full year representing 26% and 40% year-over-year increases in those periods, respectively. A number of factors are contributing to continued strong demand for RYLAZE. RYLAZE has been almost universally adopted in pediatric asparaginase-based oncology protocols in the U.S., and we continue to see strong adoption of the new Monday, Wednesday, Friday dosing regimen. We are also seeing increased usage of RYLAZE 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.

Renee Gala: Moving to oncology, slide 11 highlights the strong performance of RYLAZE in 2023, which contributed to our total oncology business exceeding a $1 billion in annual revenue for the first time. RYLAZE delivered net product sales of approximately $102 million for the fourth quarter of 2023 and approximately $394 million for the full year representing 26% and 40% year-over-year increases in those periods, respectively. A number of factors are contributing to continued strong demand for RYLAZE. RYLAZE has been almost universally adopted in pediatric asparaginase-based oncology protocols in the U.S., and we continue to see strong adoption of the new Monday, Wednesday, Friday dosing regimen. We are also seeing increased usage of RYLAZE 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 RYLAZE in the treatment of adolescents and young adults, or the AYA market.

Bruce Cozadd: Moving to oncology, slide 11 highlights the strong performance of Rylaze in 2023, which contributed to our total oncology business exceeding $1 billion in annual revenue for the first time. Rylaze delivered net product sales of approximately $102 million for Q4 2023 and approximately $394 million for the full year, representing 26% and 40% year-over-year increases in those periods, respectively. A number of factors are contributing to continued strong demand for Rylaze. Rylaze has been almost universally adopted in pediatric asparaginase-based oncology protocols in the US, and we continue to see strong adoption of the new Monday, Wednesday, Friday dosing regimen.

Renée Galá: Moving to oncology, slide 11 highlights the strong performance of Rylaze in 2023, which contributed to our total oncology business exceeding $1 billion in annual revenue for the first time. Rylaze delivered net product sales of approximately $102 million for Q4 2023 and approximately $394 million for the full year, representing 26% and 40% year-over-year increases in those periods, respectively. A number of factors are contributing to continued strong demand for Rylaze. Rylaze has been almost universally adopted in pediatric asparaginase-based oncology protocols in the US, and we continue to see strong adoption of the new Monday, Wednesday, Friday dosing regimen.

Renee: Moving to oncology slide 11 highlights the strong performance of release in 2023, which contributed to our total oncology business exceeding $1 billion in annual revenue for the first time.

Renee: Riley delivered net product sales of approximately $102 million for the fourth quarter 2023, and approximately $394 million for the full year, representing 26% and 40% year over year increases in those periods respectively.

Renee: A number of factors are contributing to continued strong demand for Riley Riley has been almost universally adopted in pediatric asparaginase based oncology protocols in the U S and we continue to see strong adoption of the new Monday Wednesday Friday dosing regimen. We are also seeing increased usage of Riley.

Bruce Cozadd: We are also seeing increased usage of Rylaze 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 Rylaze in the treatment of adolescents and young adults, or the AYA market. Turning to slide 12 in Zepzelca, net product sales for Q4 increased 3% year-over-year to $74 million. For the full year 2023, net product sales were $289.5 million, up 7% year-over-year.

Renée Galá: We are also seeing increased usage of Rylaze 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 Rylaze in the treatment of adolescents and young adults, or the AYA market. Turning to slide 12 in Zepzelca, net product sales for Q4 increased 3% year-over-year to $74 million. For the full year 2023, net product sales were $289.5 million, up 7% year-over-year.

Renee: And a L. L patients due to some of the benefits of its short acting profile relative to current first line of spirit <unk> therapies, including switches from these first line therapies due to tolerability concerns and side effects.

Renee Gala: In addition, we have an opportunity for continued growth with increasing use of RYLAZE in the treatment of adolescents and young adults, or the AYA market. Turning to slide 12 in ZEPZELCA, Net product sales for the fourth quarter increased 3% year-over-year to $74 million. For the full year 2023, net product sales were $289.5 million, up 7% year-over-year. We have established ZEPZELCA 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. Since its launch, ZEPZELCA has generated almost $900 million in revenue, and is proving to be a highly accretive and well-executed corporate development transaction. In addition to the second-line setting, there remains an unmet need for patients in earlier lines of therapy.

Renee Gala: In addition, we have an opportunity for continued growth with increasing use of RYLAZE in the treatment of adolescents and young adults, or the AYA market.

Turning to slide 12, and <unk> net product sales for the fourth quarter increased 3% year over year to $74 million.

Renee Gala: Turning to slide 12 in ZEPZELCA, Net product sales for the fourth quarter increased 3% year-over-year to $74 million. For the full year 2023, net product sales were $289.5 million, up 7% year-over-year. We have established ZEPZELCA 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. Since its launch, ZEPZELCA has generated almost $900 million in revenue, and is proving to be a highly accretive and well-executed corporate development transaction. In addition to the second-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.

Renee: For the full year 2023, net product sales were $289 $5 million up 7% year over year, we have established <unk> as the number one treatment for second line small cell lung cancer patients and we continue to hear positive feedback from health care providers on its clinical benefit.

Bruce Cozadd: We have established Zepzelca 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, ease of use, and administration for patients and their healthcare practices. Since its launch, Zepzelca has generated almost $900 million in revenue and is proving to be a highly accretive and well-executed corporate development transaction. In addition to the second-line setting, there remains an unmet need for patients in earlier lines of therapy. The ongoing phase 3 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? Thanks, Renée.

Renée Galá: We have established Zepzelca 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, ease of use, and administration for patients and their healthcare practices. Since its launch, Zepzelca has generated almost $900 million in revenue and is proving to be a highly accretive and well-executed corporate development transaction. In addition to the second-line setting, there remains an unmet need for patients in earlier lines of therapy. The ongoing phase 3 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?

Renee: And ease of use and administration for patients and their health care practices.

Renee: Since its launch ZIP silica has generated almost $900 million in revenue and it's proving to be a highly accretive and well executed corporate development transactions.

Renee: In addition to the second 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.

In addition to the second line setting there remains an unmet need for patients in earlier lines of therapy.

Renee Gala: 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.

Renee Gala: With that, I'll turn it over to Rob for an update on our pipeline and upcoming milestones. Rob.

Renee: Bob for an update on our pipeline and upcoming milestones Rob.

Rob Iannone: Thanks, Renée.

Rob Iannone: Thanks, Renee. 2024 represents an exciting time for us on the R&D front. And we anticipate multiple and 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 zanidatamab, we anticipate completing our rolling BLA submission for accelerated approval of zanidatamab in second line biliary tract cancer, or BTC, in the first half of this year. 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 III first line gastroesophageal adenocarcinoma, or GEA trial. If positive, we expect this trial would support a registration. I'll speak more to our zanidatamab development plan in just a moment.

Bruce Cozadd: 2024 represents an exciting time for us on the R&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 Zanidatamab, we anticipate completing our rolling BLA submission for accelerated approval of Zanidatamab in second-line biliary tract cancer, or BTC, in the first half of this year. 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 Zanidatamab development plan in just a moment.

Rob Iannone: 2024 represents an exciting time for us on the R&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 Zanidatamab, we anticipate completing our rolling BLA submission for accelerated approval of Zanidatamab in second-line biliary tract cancer, or BTC, in the first half of this year. 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 Zanidatamab development plan in just a moment.

Rob: 2024 represents an exciting time for us on the R&D front, and we anticipate multiple meaningful catalysts across oncology and neuroscience.

Rob: On slide 14.

Rob: We've provided an overview of the key clinical programs and our diversified pipeline.

Bob: I'll highlight several milestones we expect to reach in the near term.

Bob: Starting with oncology incentive data man.

Bob: We anticipate completing our rolling BLA submission for accelerated approval of standard data Mab in second line biliary tract cancer, where BTC in the first half of this year.

And I'm excited to report that we recently initiated our first line BTC trial.

Bob: Additionally, we are targeting late this year to report topline data from the ongoing phase III first line gastroesophageal adenocarcinoma trial.

Bob: Positive we expect this trial would support a registration.

Bob: I'll speak more to our <unk> data Mab development plan in just a moment.

Bruce Cozadd: We're also pleased with the progress of the Zepzelca first-line trial, which completed enrollment in January of this year. Top-line progression-free survival data for Zepzelca 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 Zepzelca. Turning to neuroscience, we expect top-line data from our phase 3 trial of Epidiolex in Japan in the second half of 2024. We also have ongoing trials for Suvecaltamide, or JZP385, in both essential tremor and Parkinson's disease tremor, with top-line data from the ET trial expected late in the first half of 2024. If trial findings are positive, we believe this trial could serve as part of a pivotal regulatory package.

Rob Iannone: We're also pleased with the progress of the Zepzelca first-line trial, which completed enrollment in January of this year. Top-line progression-free survival data for Zepzelca 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 Zepzelca. Turning to neuroscience, we expect top-line data from our phase 3 trial of Epidiolex in Japan in the second half of 2024. We also have ongoing trials for Suvecaltamide, or JZP385, in both essential tremor and Parkinson's disease tremor, with top-line data from the ET trial expected late in the first half of 2024. If trial findings are positive, we believe this trial could serve as part of a pivotal regulatory package.

Rob Iannone: We're also pleased with the progress of the ZEPZELCA first line trial, which completed enrollment in January of this year. Top line progression-free survival data for ZEPZELCA in combination with TECENTRIQ and 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 ZEPZELCA. Turning to neuroscience, we expect top line data from our Phase three III trial of EPIDIOLEX in Japan in the second half of 2024. We also have ongoing trials for SUVECALTAMIDE or JZP385 to both essential tremor and Parkinson's disease tremor with top line data from the ET trial expected late in the first half of 2024. If trial findings are positive, we believe this trial could serve as part of a pivotal regulatory package.

Bob: Top line progression free survival data for <unk> in combination with to centric in first line extensive stage small cell lung cancer is expected at the end of 2020 for early 2025.

Bob: If approved this indication would enable more patients with small cell lung cancer to potentially benefit from longer duration of therapy with <unk>.

Bob: Turning to neuroscience, we expect topline data from our phase III trials Epidiorite in Japan in the second half of 2024.

Bob: We also have ongoing trials for <unk> for <unk> hundred five in both essential tremor in Parkinson's disease tremor with top line data from the <unk> trial expected late in the first half of 2024.

Bob: Trial findings are positive we believe this trial could serve as part of a pivotal regulatory package.

Bruce Cozadd: Slide 15 provides more detail on our development plan for Zanidatamab. We have meaningfully progressed Zanidatamab development across indications since bringing it to Jazz last year, and based on the totality of the data, we're highly confident in this molecule as a differentiated therapy for HER2-expressing cancers. I'll note that we are hosting an R&D day on 19 March that will focus exclusively on Zanidatamab, including perspectives from GEA and breast cancer KOLs. Zanidatamab 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 Zanidatamab 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 Zanidatamab.

Rob Iannone: Slide 15 provides more detail on our development plan for Zanidatamab. We have meaningfully progressed Zanidatamab development across indications since bringing it to Jazz last year, and based on the totality of the data, we're highly confident in this molecule as a differentiated therapy for HER2-expressing cancers. I'll note that we are hosting an R&D day on 19 March that will focus exclusively on Zanidatamab, including perspectives from GEA and breast cancer KOLs. Zanidatamab 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 Zanidatamab to improve care for early and late-stage breast cancer patients.

Rob Iannone: Slide 15 provides more detail on our development plan for zanidatamab. We have meaningfully progressed zanidatamab 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&D day on March 19th that will focus exclusively on zanidatamab, including perspectives from GEA and breast cancer KOLs. Zanidatamab 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 zanidatamab to improve care for early and late-stage breast cancer patients.

Bob: We have meaningfully progressed standard data mab development across indications since bringing it to jazz last year.

Bob: And based on the totality of the data we're highly confident in this molecule as a differentiated therapy for her to expressing cancers.

Bob: I'll note that we are hosting an R&D day on March 19.

Bob: We'll focus exclusively on Saturday to Mab include.

Bob: Including perspectives from Gea and breast cancer Kols.

Bob: Yeah.

Bob: Now the data map has shown compelling activity across a broad range of her two positive tumors and our development plan represents a robust investigation of this molecule in multiple tumor types as outlined on this slide.

Bob: In addition to our BTC and <unk> programs, we see meaningful opportunity presented data map to improve care for early and late stage breast cancer patients.

Rob Iannone: Slide 16 highlights one of the most critical factors contributing to our enthusiasm around Zanidatamab.

Rob Iannone: Slide 16 highlights one of the most critical factors contributing to our enthusiasm around zanidatamab. Specifically, the data generated to date has demonstrated zanidatamab 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 zanidatamab starts with BTC, an area of high unmet patient needs where there are currently no approved HER2 therapies. We believe coming to market in BTC will enable a fast-to-market strategy where we can leverage supplemental BLA findings and other indications. GEA is the next potential indication to follow BTC, and we believe a 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. Now I will turn the call over to Bruce for a financial update. Bruce?

Bruce Cozadd: Specifically, the data generated to date has demonstrated Zanidatamab 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 Zanidatamab starts with BTC, an area of high unmet patient need where there are currently no approved HER2 therapies. We believe coming to market in BTC will enable a fast-to-market strategy where we can leverage supplemental BLA findings and other indications. GEA is the next potential indication to follow BTC, and we believe a 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.

Rob Iannone: Specifically, the data generated to date has demonstrated Zanidatamab 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 Zanidatamab starts with BTC, an area of high unmet patient need where there are currently no approved HER2 therapies. We believe coming to market in BTC will enable a fast-to-market strategy where we can leverage supplemental BLA findings and other indications. GEA is the next potential indication to follow BTC, and we believe a 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.

Specifically the data generated to date has demonstrated that a data map activity as monotherapy in <unk>.

Bob: Combination with other agents in patients previously treated with other her two agents.

Bob: And results in durable responses with encouraging progression free survival and overall survival data.

Bob: Our development strategy presented data map starts with BTC and area of high unmet patient need.

Bob: Where there are currently no approved her two therapies.

Bob: We believe coming to market in BTC will enable a faster market strategy, where we can leverage supplemental BLA filings and other indications.

Bob: <unk> is the next potential indication to follow PTC and we believe prior approval in BTC may accelerate adoption into GE treatment guidelines and protocols.

Bob: 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.

Bruce Cozadd: 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. Now I will turn the call over to Bruce for a financial update. Bruce? 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-K. In Q4 2023, we achieved more than $1 billion in total revenues, and for full year 2023, we recorded more than $3.8 billion in total revenues, representing 5% growth over full year 2022.

Rob Iannone: 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. Now I will turn the call over to Bruce for a financial update. Bruce?

Bob: 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 her two positive cancers.

Bob: Now I will turn the call over to Bruce for a financial update Bruce.

Bruce Cozadd: 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-K. In Q4 2023, we achieved more than $1 billion in total revenues, and for full year 2023, we recorded more than $3.8 billion in total revenues, representing 5% growth over full year 2022.

Bruce C. Cozadd: 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-K. In the fourth quarter of 2023, we achieved more than $1 billion in total revenues. And for full year 2023, we recorded more than $3.8 billion in total revenues, representing 5% growth over full year 2022. 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 three key growth drivers.

Bruce: In the fourth quarter of 2023, we achieved more than $1 billion in total revenues and for full year 2023, we reported more than $3 $8 billion in total revenues, representing 5% growth over full year 2022.

Bruce Cozadd: 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 three key growth drivers. Turning to slide 19, our full year 2023 non-GAAP adjusted net income was approximately $1.3 billion, 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 $1.1 billion of cash from operations for the full year 2023 and ended the year with $1.6 billion in cash on hand.

Bruce: We were pleased to deliver growth despite headwinds from the introduction of both branded and AG high sodium oxalate competition with our full year results driven by continued growth in both neuroscience and oncology, including double digit growth from each of our three key growth drivers.

Bruce C. Cozadd: Turning to slide 19, our full year 2023 non-GAAP adjusted net income was approximately $1.3 billion 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 $1.1 billion of cash from operations for the full year 2023 and ended the year with $1.6 billion 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&D programs, as well as corporate development opportunities. We are pleased to share our full year financial guidance for 2024, beginning on slide 20.

And we reported non-GAAP adjusted EPS of $18 29.

Bruce: We continue to generate significant cash from our business demonstrating the strength and diversity of our global portfolio.

Bruce: We recorded approximately $1 $1 billion of cash from operations for the full year 2023 and ended the year with $1 $6 billion in cash on hand.

Bruce Cozadd: Our strong overall financial position and operating cash flows mean we have significant flexibility to invest in priority commercial and R&D programs, as well as corporate development opportunities. We are pleased to share our full year financial guidance for 2024, beginning on slide 20. Our 2024 total revenue guidance range of $4 to 4.2 billion represents 7% year-over-year top-line growth at the midpoint. We expect double-digit percentage revenue growth of Xywav, Epidiolex, and Rylaze combined to drive total revenue growth this year. Our 2024 neuroscience revenue guidance of $2.8 to 2.95 billion reflects the expected growth of Xywav 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 million in 2024.

Bruce: Our strong overall financial position and operating cash flows.

Bruce: We have significant flexibility to invest in priority commercial and R&D programs as well as corporate development opportunities.

Bruce C. Cozadd: We are pleased to share our full year financial guidance for 2024, beginning on slide 20. Our 2024 total revenue guidance range of $4 billion to $4.2 billion represents 7% year-over-year top line growth at the midpoint. We expect double digit percentage revenue growth of XYWAV, EPIDIOLEX and RYLAZE combined to drive total revenue growth this year. Our 2024 neuroscience revenue guidance of $2.8 billion to $2.95 billion reflects the expected growth of XYWAV 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 million in 2024. Our 2024 oncology revenue guidance range of $1.12 billion to $1.22 billion reflects expectations of continued double-digit growth for this therapeutic area. I'd like to draw your attention to several items on slide 21.

Bruce: We are pleased to share our full year financial guidance for 2024, beginning on slide 20.

Bruce C. Cozadd: Our 2024 total revenue guidance range of $4 billion to $4.2 billion represents 7% year-over-year top line growth at the midpoint. We expect double digit percentage revenue growth of XYWAV, EPIDIOLEX and RYLAZE combined to drive total revenue growth this year. Our 2024 neuroscience revenue guidance of $2.8 billion to $2.95 billion reflects the expected growth of XYWAV 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 million in 2024. Our 2024 oncology revenue guidance range of $1.12 billion to $1.22 billion reflects expectations of continued double-digit growth for this therapeutic area. I'd like to draw your attention to several items on slide 21.

Bruce: Represents 7% year over year topline growth at the midpoint.

Bruce: We expect double digit percentage revenue growth of <unk>, <unk> and <unk> combined to drive total revenue growth this year.

Bruce: Our 2020 for neuroscience revenue guidance of $2 eight to $2 95 billion.

Bruce: Reflects the expected growth of sideways, NIH and <unk> offset by the expected decline in Xyrem.

Bruce: Note. This guidance is inclusive of AG royalties, which we expect to exceed $200 million in 2024.

Bruce Cozadd: Our 2024 oncology revenue guidance range of $1.12 to 1.22 billion reflects expectations of continued double-digit growth for this therapeutic area. I'd like to draw your attention to several items on slide 21. With regard to operating expenses, our SG&A guidance range is $1.17 to 1.23 billion. The expected increase in SG&A in 2024 over 2023 will largely be a result of continued investments in our key growth drivers, including Xywav IH initiatives, commercial support for Epidiolex in the US, where we know the market is promotionally sensitive, geographic expansion of Epidiolex outside the US, and educational efforts for Rylaze in AYA.

Bruce: Our 2020 for oncology revenue guidance range of $1, one two to $1 billion to $2 billion.

Bruce: It reflects expectations of continued double digit growth for this therapeutic area.

Bruce C. Cozadd: I'd like to draw your attention to several items on slide 21. With regard to operating expenses, our SG&A guidance range is $1.17 billion to $1.23 billion. The expected increase in SG&A in 2024 over 2023 will largely be a result of continued investments and our key growth drivers, including XYWAV 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., and educational efforts for RYLAZE in AYA. Our R&D guidance range of $800 million to $850 million represents an increase of 5% at the midpoint compared to 2023, driven by planned continued investment in our robust zanidatamab development program. Both SG&A and R&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 billion to $1.35 billion. This reflects anticipated investments in our commercial growth drivers and pipeline enabled by top line growth and disciplined and strategic capital allocation.

Bruce: I'd like to draw your attention to several items on slide 21.

Bruce C. Cozadd: With regard to operating expenses, our SG&A guidance range is $1.17 billion to $1.23 billion. The expected increase in SG&A in 2024 over 2023 will largely be a result of continued investments and our key growth drivers, including XYWAV 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., and educational efforts for RYLAZE in AYA. Our R&D guidance range of $800 million to $850 million represents an increase of 5% at the midpoint compared to 2023, driven by planned continued investment in our robust zanidatamab development program. Both SG&A and R&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 billion to $1.35 billion. This reflects anticipated investments in our commercial growth drivers and pipeline enabled by top line growth and disciplined and strategic capital allocation.

Bruce: The expected increase in SG&A in 2024 over 2023 will largely be a result of continued investments in our key growth drivers, including XI wave IH initiatives commercial support for <unk> in the U S, where we know the market is promotional sensitive gene.

Bruce: Geographic expansion of epic dialects outside the U S and educational efforts for railways in Hawaii.

Bruce Cozadd: Our R&D guidance range of $800 to $850 million represents an increase of 5% at the midpoint compared to 2023, driven by planned continued investment in our robust Zanidatamab development program. Both SG&A and R&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 to $1.35 billion. 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. In 2023, we delivered on our neuroscience, oncology, and total revenue guidance.

Bruce: Our R&D guidance range of $800 million to $850 million represents an increase of 5% at the midpoint compared to 2023 driven by planned continued investment in our robust is there any data map development program.

Bruce: Both SG&A and R&D guidance at the midpoint represent the same percentages of total revenue compared to 2023.

Bruce: On the bottom line, we expect adjusted net income in 2024 to be in line with FY2023 with a guidance range of $1 $2 75 to 135 billion. This reflects anticipated investments in our commercial growth drivers and pipeline enabled by top line growth and disciplined.

Strategic capital allocation.

Bruce C. Cozadd: I'll conclude our prepared remarks on slide 23. In 2023, we deliver 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 XI wave Epidiorite and reilly's on a combined basis, we expect these to grow by <unk>. Double digits again in 2024. This is a very exciting time for <unk> on the R&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. In summary, we are poised to deliver top line growth in multiple pipeline catalysts in 2024 and longer term with our expanding product portfolio R&D progress and focus on operational excellence. We believe we are well positioned to achieve vision 2025 and deliver further diversification.

Bruce C. Cozadd: I'll conclude our prepared remarks on slide 23. In 2023, we deliver 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, XYWAV, EPIDIOLEX, and RYLAZE. 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&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 Change: In 2023, we deliver 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 XI wave Epidiorite and reilly's on a combined basis, we expect these to grow by <unk>.

Bruce Cozadd: On the commercial side, our 2023 performance was driven by combined double-digit growth of key products Xywav, Epidiolex, and Rylaze. 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&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. In summary, we are poised to deliver top-line growth and multiple pipeline catalysts in 2024. Longer term, with our expanding product portfolio, R&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.

Speaker Change: Double digits again in 2024.

Speaker Change: This is a very exciting time for <unk> on the R&D front as we continue to advance our pipeline and invest in long term growth with multiple catalysts expected in the near term.

Speaker Change: As always we remain focused on operational excellence and strategic capital allocation with corporate development remaining an opportunity for additional growth and diversification.

Speaker Change: In summary, we are poised to deliver top line growth in multiple pipeline catalysts in 2024 and longer term with our expanding product portfolio R&D progress and focus on operational excellence. We believe we are well positioned to achieve vision 2025 and deliver further diversification.

Bruce C. Cozadd: 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&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&A.

Bruce Cozadd: Longer term, with our expanding product portfolio, R&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.

Speaker Change: <unk> 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&A.

Bruce Cozadd: That concludes our prepared remarks. I would now like to turn the call over to the operator to open the line for Q&A. And thank you. At this time, I would like to remind everyone, in order to ask a question, press star and then the number one on your telephone keypad. To be able to take as many questions as possible, we ask that you please limit yourself to one question. We will pause for just a moment to compile the Q&A roster. We will take our first question from Jessica Fye with J.P. Morgan. Your line is open. Hey there. Good afternoon. Thanks for taking my question. We're hearing worries about Xywav's position in narcolepsy, despite what looks like sleep neuro guidance clearly ahead of consensus.

Bruce Cozadd: That concludes our prepared remarks. I would now like to turn the call over to the operator to open the line for Q&A.

Operator: And thank you. At this time, I would like to remind everyone, in order to ask a question, press star and then the number one on your telephone keypad. To be able to take as many questions as possible, we ask that you please limit yourself to one question. We will pause for just a moment to compile the Q&A roster. We will take our first question from Jessica Fye with J.P. Morgan. Your line is open.

Operator: Thank you. At this time, I would like to remind everyone: In order to ask a question press star and then the number one on your telephone keypad. To be able to take as many questions as possible, we ask that you please limit yourself to one question. We'll pause for just a moment to compile the Q&A roster. And we will take our first question from Jessica Fye with JP Morgan. Your line is open.

At this time I would like to remind everyone in order to ask a question Press Star and then the number one on your telephone keypad.

Speaker Change: To be able to take as many questions as possible. We ask that you. Please limit yourself to one question.

Speaker Change: We'll pause for just a moment to compile the Q&A roster.

Speaker Change: Yeah.

And we will take our first question from Jessica Fye with J P. Morgan Your line is open.

Jessica Fye: Hey there. Good afternoon. Thanks for taking my question. We're hearing worries about Xywav's position in narcolepsy, despite what looks like sleep neuro guidance clearly ahead of consensus.

Jessica Fye: Hey there. Good afternoon. Thanks for taking my question. We're seeing worries about XYWAV’s position in narcolepsy, despite what looks like sleep neuro guidance, slightly 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 XYWAV in that setting? Thank you.

Jessica Fye: Were staring worries about XI waves physician in narcolepsy, despite what looks like sleep neuro guidance slightly ahead of consensus can you talk about what youre seeing competitively in narcolepsy right now and maybe set expectations for what you think the outlook is for <unk> in that setting. Thank you.

Bruce Cozadd: 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 Xywav in that setting? Thank you. Yeah. Hi, Jess. Thanks for the question. Renée, maybe I'll turn that one over to you. Sure. Yeah. Happy to comment. Thanks, Jess. So at a high level, as we look at Xywav for 2024, as we noted on the call, we do expect it to be an important growth driver, one of three, as we look at where we expect growth on the top line across the year. We do see Xywav 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.

Jessica Fye: 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 Xywav in that setting? Thank you.

Bruce C. Cozadd: Yes, hi, Jess. Thanks for the question. Renee, maybe I'll turn that one over to you.

Bruce Cozadd: Yeah. Hi, Jess. Thanks for the question. Renée, maybe I'll turn that one over to you.

Speaker Change: Yes, Hi, Jeff. Thanks for the question Rene maybe I'll turn that one over to you.

Renée Galá: Sure. Yeah. Happy to comment. Thanks, Jess. So at a high level, as we look at Xywav for 2024, as we noted on the call, we do expect it to be an important growth driver, one of three, as we look at where we expect growth on the top line across the year. We do see Xywav 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.

Renee Gala: Sure, yes, happy to comment. Thanks, Jess. So at a high level, as we look at XYWAV for 2024, as we noted on the call, we do expect it to be an important growth driver, one of three, as we look at where we expect growth on the top line across the year. We do see XYWAV continuing to resonate as a differentiated therapy, as the only low. sodium oxybate, the number one treatment of narcolepsy, and then, of course, the only drug approved for IH. What we're seeing in terms of the market is we are seeing the majority of new to oxybate patients starting on XYWAV. We do believe it will remain the oxybate of choice. And that said, as we're looking at Q4, as we've said, we do expect some patients to try LUMRYZ given there are now many more patients on XYWAV than XYREM, naturally, we would expect some impact there. So, as we look at exiting the fourth quarter, we had more than 9, 500 narcolepsy patients ending the year. Keep in mind also that our patient number is a net number, so it reflects the adds from the quarter less in a discontinuation that we had. Also, in the fourth quarter, 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 with seasonal, and we don't expect it to continue given how we're refining those programs.

Rene: At a high level as we look at <unk> for 2024, as we noted on the call. We do expect it to be an important growth driver.

Rene: One of three and we look at where we expect growth on the top line across the year.

Rene: We do see <unk>, continuing to resonate as a differentiated therapy as the only low 30 amongst debate the number one treatment of narcolepsy and then of course, the only drug approved for <unk>.

Rene: I H, what we're seeing in terms of the market as we are seeing the majority of new to oxo patient starting on highways. We do believe it will remain the oxidative choice.

Bruce Cozadd: What we're seeing in terms of the market is we are seeing the majority of new-to-oxybate patients starting on Xywav. We do believe it will remain the oxybate choice. And that said, as we're looking at Q4, as we've said, we do expect some patients to try Lumryz. Given there are now many more patients on Xywav than Xyrem, naturally, we would expect some impact there. So as we look at exiting the fourth quarter, we had more than 9,500 narcolepsy patients ending the year. Keep in mind also that our patient number is a net number, so it reflects the adds from the quarter, less any discontinuations that we had. Also, in the fourth quarter, we did see an increase in our non-revenue bottles as we continue to refine our patient support services program.

Renée Galá: What we're seeing in terms of the market is we are seeing the majority of new-to-oxybate patients starting on Xywav. We do believe it will remain the oxybate choice. And that said, as we're looking at Q4, as we've said, we do expect some patients to try Lumryz. Given there are now many more patients on Xywav than Xyrem, naturally, we would expect some impact there. So as we look at exiting the fourth quarter, we had more than 9,500 narcolepsy patients ending the year. Keep in mind also that our patient number is a net number, so it reflects the adds from the quarter, less any discontinuations that we had. Also, in the fourth quarter, we did see an increase in our non-revenue bottles as we continue to refine our patient support services program.

Rene: That said as we're looking at Q4 as we've said we do expect some patients to try loomer is.

Rene: Given there are now many more patients on <unk> than Xyrem naturally we would expect some impact there. So as we look at exiting the fourth quarter, we had more than 9500 narcolepsy patients ending the year keep in mind also that our patient number is a net number so it reflects they add.

Rene: Adds from the every quarter from the quarter less any discontinuation that we had also in the fourth quarter. We did see an increase in our non revenue bottles as we continue to refine our patient support services program.

Bruce Cozadd: 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. And then I'll just say that as we look forward, we do believe that every high-sodium patient is a potential Xywav patient.

Renée Galá: 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. And then I'll just say that as we look forward, we do believe that every high-sodium patient is a potential Xywav patient.

Rene: We are seeing an increase in programs that essentially seek to take advantage of our affordability programs to increase the seasonal and we don't expect that to continue given how were refining those programs.

Renee Gala: And then finally, keep in mind within the fourth quarter, 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. And then I'll just say that as we look forward, we do believe that every high sodium patient is a potential XYWAV patient. In particular, as we see decreasing commercial coverage for XYREM, we expect those patients to shift therapy, either to authorize generics, which of course we receive a significant royalty on, or to fix that high sodium branded therapy, or importantly to XYWAV, which will be an additional driver of growth in 2024 for narcolepsy, with probably more of our growth coming from an idiopathic hypersomnia.

Rene: Starting therapy as a patient that's discontinuing and then I'll just say that as we look forward. We do believe that every high sodium patient as a potential <unk> patient in particular as we see decreasing commercial coverage for Xyrem, we expect those patients to shift therapy, either to authorized generics which of course, we are.

Bruce Cozadd: In particular, as we see decreasing commercial coverage for Xyrem, we expect those patients to shift therapy, either to authorized generics, which, of course, we receive a significant royalty on, or to fixed-dose high-sodium branded therapy, or importantly, to Xywav, which will be an additional driver of growth in 2024 for narcolepsy, with probably more of our growth coming from idiopathic hypersomnia. We will take our next question from Marc Goodman with Leerink Partners. Your line is open. Yeah. Can you give us a little color just on the oncology portfolio? I mean, you have products Defitelio, Vyxeos, Zepzelca, or Rylaze. I'm sorry, Rylaze. I still say that, Bruce. I apologize. Any color you can give us just on the quarters? I mean, Defitelio and Vyxeos is obviously much higher than expected. The other two products flattish quarter-over-quarter. So anything you can provide would be helpful.

Renée Galá: In particular, as we see decreasing commercial coverage for Xyrem, we expect those patients to shift therapy, either to authorized generics, which, of course, we receive a significant royalty on, or to fixed-dose high-sodium branded therapy, or importantly, to Xywav, which will be an additional driver of growth in 2024 for narcolepsy, with probably more of our growth coming from idiopathic hypersomnia.

We see the significant royalty on or to fixed dose high high sodium branded therapy, or importantly to XI 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.

Operator: And we will take our next question from Marc Goodman with Leerink Partners. Your line is open.

Marc Goodman: Yeah. Can you give us a little color just on the oncology portfolio? I mean, you have products Defitelio, Vyxeos, Zepzelca, or Rylaze. I'm sorry, Rylaze. I still say that, Bruce. I apologize. Any color you can give us just on the quarters? I mean, Defitelio and Vyxeos is obviously much higher than expected. The other two products flattish quarter-over-quarter. So anything you can provide would be helpful.

Marc Goodman: Yes, can you give us a little color just on the oncology portfolio? I mean, you have products, DEFITELIO, VYXEOS, ZEPZELCA, ERWINAZE--I'm sorry, RYLAZE, 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. The other two products flattish quarter-to-quarter, so anything you can provide would be helpful. Thanks.

Marc Harold Goodman: Any color you can give us just on the quarter. So many <unk> and fixed he is obviously much higher than expected.

Marc Harold Goodman: The two products flattish quarter to quarter. So anything you can provide would be helpful. Thanks.

Bruce Cozadd: Thanks. Yeah. Marc, 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 into the Defitelio, Vyxeos side. We've been more focused on the growth in Zepzelca, but particularly on our strong performance with Rylaze. And maybe I'll turn it over to Renée to comment a little bit on Rylaze. Yeah. Thanks, Bruce. And thanks for the question, Marc. I would say certainly echoing the variability with respect to Rylaze in particular, we did see some seasonality at the end of Q4 going into the holidays.

Bruce C. Cozadd: Yes, Marc, you're not the only one that occasionally refers to a prior product name. You know, 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. We've been more focused on the growth in ZEPZELCA, but particularly on our strong performance with RYLAZE, and maybe I'll turn it over to Renee to comment a little bit on RYLAZE.

Speaker Change: I'll say for some of our products, we do see significant quarter to quarter variability, particularly in the sort of <unk>.

Speaker Change: Rare diseases. This has been true of <unk> for years, So I wouldn't read too much in on the desktop side.

Speaker Change: We've been more focused on the growth in silica, but particularly on our strong performance with Riley. So maybe I'll turn it over to Renee to comment a little bit on Riley's.

Renée Galá: Yeah. Thanks, Bruce. And thanks for the question, Marc. I would say certainly echoing the variability with respect to Rylaze in particular, we did see some seasonality at the end of Q4 going into the holidays.

Renee Gala: Yes, thanks, Bruce, and thanks for the question, Marc. I would say certainly echoing the variability with respect to RYLAZE in particular, we did see some seasonality at the end of the fourth quarter 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 RYLAZE. Importantly, we do see RYLAZE as a growth driver in 2024. 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 fourth quarter, and we also began a rolling launch in Europe late in the year.

Renee: The variability with respect to <unk> in particular, we did see some seasonality at the end of the fourth quarter going into the holidays.

Bruce Cozadd: This is a relatively small market in terms of the rare population here with respect to the use that we see in Rylaze. Importantly, we do see Rylaze as a growth driver in 2024. 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 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 Zepzelca, 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.

Renée Galá: This is a relatively small market in terms of the rare population here with respect to the use that we see in Rylaze. Importantly, we do see Rylaze as a growth driver in 2024. 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 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 Zepzelca, 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.

Renee: This is a relatively small market in terms of the rare population here with respect to that and they use that we see and Reilly's importantly, we do see Riley as a growth driver in 2024.

Renee: Just a reminder, due to supply constraints with <unk>. If we were never really able to fully understand the market potential for that product, but we're continuing to see.

Renee: Strong demand overall in the fourth quarter and we also began a rolling launch in Europe late in the year.

Renee Gala: 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 ZEPZELCA, 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 but we do as Bruce said have some variability quarter- to-quarter in that area as well.

Renee: A strong contributor to growth in 2024, but we're pleased we were able to get that underway and then with respect to <unk>. We've established us 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.

Bruce Cozadd: 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'd mentioned, and seeing additional use there. But we do, as Bruce said, have some variability quarter to quarter in that area as well. We will take our next question from Jason Gerberry with Bank of America. Your line is open. Hey. Good evening. Thanks for taking my question. My question just how you foresee with Zanidatamab the front-line 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, that that should facilitate a broader label than Merck secured with its Keynote-811 regimen?

Renée Galá: 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'd mentioned, and seeing additional use there. But we do, as Bruce said, have some variability quarter to quarter in that area as well.

Renee: That study either late this year or early the next year, we continue to hear positive feedback.

Renee: From Hcp's on the clinical benefit the ease of use as I had mentioned.

Renee: Seeing additional use there, but we do as Bruce said had some bulk some variability quarter to quarter in that area as well.

Operator: We will take our next question from Jason Gerberry with Bank of America. Your line is open.

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

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

Jason Gerberry: Hey. Good evening. Thanks for taking my question. My question just how you foresee with Zanidatamab the front-line 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, that that should facilitate a broader label than Merck secured with its Keynote-811 regimen?

Jason Garberry: Hi, good evening. Thanks for taking my question. My question just how you foresee with zani the frontline GEA differentiating in the PD-1 negative subpopulation if you aren't stratifying patients on the basis of PD-1 status. So, is the thought here that as long as that subpopulation doesn't produce a discordant result versus the all comer group that that should facilitate a broader label than Merck secured with this KEYNOTE-811 regimen. Just kind of wondering how you can kind of paint that picture. Thanks.

Jason: My question just.

Jason: How do you foresee with Fannie the frontline gea differentiating in the PD Lone negative subpopulation, if you arent stratify patients on the basis of PD Lone status. So is the thought here that.

Jason: As long as that subpopulation does it produce at this Gordon result versus the all comer group, but that should facilitate a broader label than in Merck secured with keynote <unk> 811 regimen, just kind of wondering how.

Bruce Cozadd: Just kind of wondering how you can kind of paint that picture. Thanks. Thanks, Jason, for the question. Rob, you want to weigh in on that? Yeah. The PD-L1 biomarker wouldn't have any predictive value for Zanidatamab 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 two experimental arms. One where Zanidatamab is combined with standard of care chemo, and we also have an arm where we add PD-1 antagonists to that, Tislelizumab, from BeiGene. 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 have been shown to benefit patients. And we think in that segment, we have the superior anti-HER2 drug.

Jason Gerberry: Just kind of wondering how you can kind of paint that picture. Thanks.

Speaker Change: You can kind of paint that picture. Thanks.

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

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

Rob Iannone: Yeah. The PD-L1 biomarker wouldn't have any predictive value for Zanidatamab 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 two experimental arms. One where Zanidatamab is combined with standard of care chemo, and we also have an arm where we add PD-1 antagonists to that, Tislelizumab, from BeiGene. 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 have been shown to benefit patients. And we think in that segment, we have the superior anti-HER2 drug.

Rob Iannone: Yes, the PD-1 biomarker wouldn't have any predictive value for zanidatamab or any other HER2 therapies. But we think we can clearly define a benefit in the PD-1 positive or negative subgroups. Of course, we have two experimental arms. Part one where zani is combined with standard of care chemo. And we also have an arm where we add PD-1 antagonists to that atezolizumab from BeiGene. And so we have an opportunity to address both the PD-1 negative group where the standard of care continues to be Herceptin chemo and the PD-1 positive group where PD-1s have been shown to benefit patients. And we think in that segment, we have the superior HER2 drug. We don't think that there will be a differential based on which PD-1 is used.

Speaker Change: In the PD lone positive or negative subgroups of course, we have two experimental arms, one where zani is combined with standard of care chemo.

Speaker Change: And we also have an arm, where we add PD, one antagonist to that because Elisa mab probation and so we have an opportunity to address both.

Speaker Change: PD Lone negative group, where the standard of care continues to be Herceptin chemo.

Speaker Change: In the PD Lone positive group, where.

Speaker Change: PD ones.

Speaker Change: Sure Ben.

Speaker Change: <unk> to benefit patients and we think in that.

Speaker Change: Segment, we have the.

Speaker Change: Superior anti <unk>.

Speaker Change: Drug we don't think that there'll be a differential.

Bruce Cozadd: We don't think that there'll be a differential based on which PD-1 is used. And we will take our next question from Amy Fadia with Needham & Company. Your line is open. 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 Lumryz? How has that impacted the total number of patients on oxybate? Do you believe that they are expanding the market or predominantly taking share? 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 depth? Thanks. Thanks, Amy, for those questions. Renée, I'll turn that one over to you. Sure. Yeah. And thank you, Amy.

Rob Iannone: We don't think that there'll be a differential based on which PD-1 is used.

Speaker Change: Just on which PD one is used.

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

Operator: And we will take our next question from Ami Fadia with Needham & Company. Your line is open.

Amy Fadia: 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 Lumryz? How has that impacted the total number of patients on oxybate? Do you believe that they are expanding the market or predominantly taking share? 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 depth? Thanks.

Ami Fadia: 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 LUMRYZ? How has that impacted the total number of patients on oxybate? Do you believe that they are expanding the market or predominantly taking share? 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 salesforce will focus on to drive additional prescribing debt? Thanks.

Amy: Going back to the <unk> market can you talk about the market dynamics, particularly.

Amy: Clearly that the entry.

Amy: Right.

Amy: How has that impacted the total number of patients on ox abate.

Amy: Do you believe that they are expanding the market or predominantly taking share and how do you envision that evolving in 2024 in your guidance.

Amy: And maybe just related to that NIH can you elaborate on where the increased sales force focused on to drive additional prescribing depth. Thanks.

Bruce Cozadd: Thanks, Amy, for those questions. Renée, I'll turn that one over to you.

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

Renée Galá: Sure. Yeah. And thank you, Amy.

Renee Gala: Sure, yes, and 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 XYWAV. Now based on as we look at 2024 for example, we expect to see a continued decline of Xyrem. We said we expect AG royalties to exceed $200 million and we expect to see XYWAV as an important growth driver. But that growth will likely be greater in IH versus narcolepsy as I 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 XYWAV, it would be natural to expect some impact to XYWAV from patients starting on branded fixed-dose high sodium LUMRYZ.

Bruce Cozadd: 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 Xywav. Now, based on as we look at 2024, for example, we expect to see a continued decline of Xyrem. We've said we expect AG royalties to exceed $200 million, and we expect to see Xywav 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 Xywav, it would be natural to expect some impact to Xywav from patients starting on branded fixed-dose high-sodium Lumryz.

Renée Galá: 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 Xywav. Now, based on as we look at 2024, for example, we expect to see a continued decline of Xyrem. We've said we expect AG royalties to exceed $200 million, and we expect to see Xywav 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 Xywav, it would be natural to expect some impact to Xywav from patients starting on branded fixed-dose high-sodium Lumryz.

Speaker Change: Starting on XI wave now based on as we look at 2024. For example, we expect to see a continued decline as Iran. We've said, we expect <unk> royalties to exceed $200 million and we expect to cease highways as an important growth driver, but that grew.

Speaker Change: Both will likely be greater and IH versus narcolepsy as I've mentioned before but the narcolepsy business is very important to us.

Speaker Change: 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 XI waves.

Speaker Change: It would be natural to expect some impact to <unk> from patients starting on branded fixed status high sodium loom rise.

Bruce Cozadd: We do continue, though, to see, as we look forward, this opportunity for some growth within narcolepsy, related to some market expansion. I think there's very little of that that we're seeing right now. 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.

Renée Galá: We do continue, though, to see, as we look forward, this opportunity for some growth within narcolepsy, related to some market expansion. I think there's very little of that that we're seeing right now. 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.

Renee Gala: We do continue though, to see as we look forward this opportunity for some growth within narcolepsy related to some market expansion. I think there's very little of that that we're seeing right now and just given if you are looking at on 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 it 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 Change: 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 oxidate now with respect to I H as we look at whats happening with that market, we continue to see.

Speaker Change: <unk>.

Speaker Change: 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 oxidate prescribers, but those who are not currently do.

Bruce Cozadd: 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. And we will take our next question from Ash Verma with UBS. Your line is open. Hi. Thanks for taking my question. So I wanted to just get your latest thoughts on what you're thinking about bridging to 2025 vision of $5 billion 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 Zepzelca, on the competitive front, there is a drug from Amgen, Tarlatamab.

Renée Galá: 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 Change: <unk> a lot of prescribing for IH.

Speaker Change: As well as broader opportunities to focus on prescribers that are less familiar with oxidate in general that have a number of patients within their practice on IH.

Operator: And we will take our next question from Ash Verma with UBS. Your line is open.

Operator: And we will take our next question from Ashish Verma with UBS. Your line is open.

Ash Verma: Hi. Thanks for taking my question. So I wanted to just get your latest thoughts on what you're thinking about bridging to 2025 vision of $5 billion 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 Zepzelca, on the competitive front, there is a drug from Amgen, Tarlatamab.

Ashish Verma: 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 billion in sales. Do you think you need the 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 ZEPZELCA on competitive front, there is a drug from Amgen, tarlatamab, if you can comment on how do you think the small cell lung cancer space might evolve? Thanks.

Ashwani Verma: I wanted to just get your latest thoughts on what Youre thinking about bridging to 2025 vision of $5 billion in sales do you think you need a business development to get there.

Ashwani Verma: And is it possible that you could reconsider the target metrics for 2025 at some point.

Ashwani Verma: And then second question, so pointed out zilkha uncompetitive from a there was a drop from Amgen.

Ashwani Verma: That amount.

Ashwani Verma: So just if you can comment on how do you think the small cell lung cancer, whose base might be well.

Bruce Cozadd: Just if you can comment on how you think the small cell lung cancer space might evolve. Thanks. Yeah. 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 billion from oxybate. And I'll remind you that we had excellent progress with Xywav in particular in 2023, and we continue to expect additional growth in 2024. Last year, we had over $1.9 billion as we moved toward the $2 billion target. Epidiolex, we said, would be a blockbuster product north of $1 billion in revenue. We're currently annualizing based on the last quarter at over $900 million and still showing nice growth both in the US and outside the US with Epidiolex. So we believe we're solidly on track for that.

Ash Verma: Just if you can comment on how you think the small cell lung cancer space might evolve. Thanks.

Bruce Cozadd: Yeah. 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 billion from oxybate. And I'll remind you that we had excellent progress with Xywav in particular in 2023, and we continue to expect additional growth in 2024. Last year, we had over $1.9 billion as we moved toward the $2 billion target. Epidiolex, we said, would be a blockbuster product north of $1 billion in revenue. We're currently annualizing based on the last quarter at over $900 million and still showing nice growth both in the US and outside the US with Epidiolex. So we believe we're solidly on track for that.

Ashwani Verma: Thanks.

Bruce C. Cozadd: 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 billion from oxybate. And I'll remind you that we had excellent progress with XYWAV in particular in 2023, and we continue to expect additional growth in 2024. Last year, we had over $1.9 billion as we moved toward the $2 billion target. EPIDIOLEX, we said, would be a blockbuster product north of $1 billion in revenue. We're currently annualizing based on the last quarter at over $900 million and still showing this growth both in the U.S. and outside the U.S. with EPIDIOLEX.

Speaker Change: Good for revenues, specifically, we had identified that as we came into 2022 is coming about $2 billion from ox abate.

Speaker Change: And I'll remind you that we had excellent progress with sideways in particular in 2023, and we continue to expect additional growth in 2020 for.

Speaker Change: Last year, we had over $1 $9 billion as we move towards the $2 billion target.

Speaker Change: At the dialects, we said would be a blockbuster product north of $1 billion in revenue.

Speaker Change: We're currently annualized based on the last quarter at over $900 million and still showing nice growth both from the U S and outside the U S. With <unk>. So we believe we're solidly on track for that.

We're currently annualized based on the last quarter at over $900 million and still showing nice growth both from the U S and outside the U S. With <unk>.

Bruce C. Cozadd: So we believe we're solidly on track for that. And we also said our oncology business would contribute north of a $1 billion in 2025, Epidiolex and oncology together contributing $2.5 billion. And we're very pleased obviously to see our oncology business grow to more than a $1 billion 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, $4.5 billion, we feel that we are on track for Vision 2025. We of course did include a placeholder of $500 million in 2025 revenues that could come from corporate development transactions done after we announced Vision 2025. Of course, that could include some revenue contributions from zanidatamab where we said we'll finish our rolling ELA submission in the first half of this year. And we're projecting that launch come in 2025 or sooner.

Bruce Cozadd: And we also said our oncology business would contribute north of $1 billion in 2025. With Epidiolex and oncology together, contributing $2.5 billion. And we were very pleased, obviously, to see our oncology business grow to more than $1 billion 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, $4.5 billion, we feel like we are on track for Vision 2025. We, of course, did include a placeholder of $500 million in 2025 revenues that could come from corporate development transactions done after we announced Vision 2025.

Speaker Change: <unk> set our oncology business with contributing north of $1 billion in 2025 without the dialect in oncology together contributing $2 5 billion.

Speaker Change: We're very pleased obviously to see our oncology business grow to more than $1 billion in.

Speaker Change: In 2023, and we've again protected nice growth of that business as you can see from our guidance for 2020 before so.

Speaker Change: Piece for $5 billion, we feel we are on track for vision 2025. We of course did include a placeholder of $500 million in 2025 revenues that could come from corporate development transactions done after we announced vision 2025.

Bruce Cozadd: Of course, that could include some revenue contribution from Zanidatamab, where we said we'll finish our rolling BLA submission in the first half of this year, and we're projecting that launch could come in 2025 or sooner. We're not suggesting that that would make up all of that $500 million in 2025, but we are in a 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 for interesting additions to our business. I'll point out we're not going to do a deal just to do a deal.

Speaker Change: Of course that could include some revenue contribution from Jamie David map, where we said we will finish our rolling BLA submission in the first half of this year and we're projecting that launch in 'twenty five or sooner.

Bruce C. Cozadd: We're not suggesting that would make up all of that $500 million 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, it furthers our strategy as an additional growth driver and provides sustainability over not just 2025, but as we look through the period 2025 to 2030. So, long answer asked to a short question, but we're making excellent progress toward Vision 2025. And on the ZEPZELCA side, maybe Rob, I'll turn that one over to you.

Speaker Change: We are in strong financial position with our cash and our cash flow to be active on the corporate development side as we continue to review it.

Speaker Change: Targets that would make for 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 it furthers our.

Bruce Cozadd: We're going to do a deal if it's a good use of our capital, 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 2030. So long answer, Ash, to a short question, but we feel we're making excellent progress toward Vision 2025. On the Zepzelca side, maybe Rob, I'll turn that one over to you. Happy to, Bruce. As you know, Tarlatamab is a very different mechanism of action than Zepzelca. The data that will support that have supported a BLA are in the third line versus Zepzelca in the second line. The safety profile for Tarlatamab is really quite different with a high risk of CRS and serious CRS, even including neurological effects.

Speaker Change: Strategy as an additional growth driver and provides sustainability over not just 2025, but as we look through the period.

Speaker Change: 5% to 2030 so.

Speaker Change: Long answer ash too.

Speaker Change: Short question, but we are making excellent progress towards vision 2025.

Speaker Change: And on the <unk>.

Speaker Change: Syed maybe Rob I'll turn that one over to you.

Rob Iannone: Happy to, Bruce. As you know, Tarlatamab is a very different mechanism of action than Zepzelca. The data that will support that have supported a BLA are in the third line versus Zepzelca in the second line. The safety profile for Tarlatamab is really quite different with a high risk of CRS and serious CRS, even including neurological effects.

Rob Iannone: Happy to, Bruce. As tarlatamab is a very different mechanism of action than ZEPZELCA. The data that will support, that have supported a BLA are in the third line versus ZEPZELCA in the second line. And the safety profile for tarlatamab 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. In contrast, ZEPZELCA has a very favorable safety profile, can be easily given as an infusion once every three weeks. And that really makes it an ideal candidate for add-on therapy in the frontline setting. And as 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 a greater proportion of patients to receive therapy for a longer time.

Rob: As you know <unk> is a very different mechanism of action than <unk> itself.

Rob: The data that will support that have supported them.

Speaker Change: In the third line.

Rob: Versus absorption in the second line.

Speaker Change: And the safety profile for <unk> was really quite different.

Rob: High risk of Crs and theories Crs, even in including neurological.

Speaker Change: FX.

Speaker Change: In.

Bruce Cozadd: That safety profile may well be a significant challenge, especially for community practitioners where many small-cell lung cancer patients are treated. In contrast, Zepzelca has a very favorable safety profile. Can be easily given as an infusion once every three weeks. That really makes it an ideal candidate for add-on therapy in the front-line setting. As you know, in partnership with Genentech, we are running a front-line trial in small-cell lung cancer. We expect top-line PFS results as early as the end of this year. That will allow a greater proportion of patients to receive therapy for a longer time. Yeah.

Rob Iannone: That safety profile may well be a significant challenge, especially for community practitioners where many small-cell lung cancer patients are treated. In contrast, Zepzelca has a very favorable safety profile. Can be easily given as an infusion once every three weeks. That really makes it an ideal candidate for add-on therapy in the front-line setting. As you know, in partnership with Genentech, we are running a front-line trial in small-cell lung cancer. We expect top-line PFS results as early as the end of this year. That will allow a greater proportion of patients to receive therapy for a longer time. Yeah.

Speaker Change: That safety profile may well be a significant challenge, especially for community practitioners, where many small cell lung cancer patients are treated.

Speaker Change: In contrast themselves because a very favorable.

Speaker Change: Safety profile can be easily given it's an infusion once every three weeks and that really makes it an ideal candidate for add on therapy in the frontline setting and as you know and partner with Genentech.

Speaker Change: We're running a frontline trial in small cell lung cancer, we expect topline PFS results as early as the end of this year.

Speaker Change: And that will allow greater proportion of patients to receive therapy for for a longer time.

Renee Gala: And to build on that further, so as we look at that opportunity in first line, we also appreciate, as Rob had mentioned, the ease of use for ZEPZELCA currently in second line, just 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.

Bruce Cozadd: And just to build on that further, so as we look at that opportunity in first line, we also appreciate, as Rob had mentioned, the ease of use for Zepzelca currently in second line, just 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. And we will take our next question from Joseph Thome with TD Cowen. Your line is open. Hi there. Good evening. Congrats on the progress, and thank you for taking my question. Maybe just one on Zanidatamab. How should we think about continued investment in the program overall? I know you outlined the breast cancer opportunity and other HER2-expressing cancers.

Renée Galá: And just to build on that further, so as we look at that opportunity in first line, we also appreciate, as Rob had mentioned, the ease of use for Zepzelca currently in second line, just 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.

Speaker Change: Yes.

Speaker Change: To build on that further so as we as we look at that opportunity in first line. We also would appreciate as Rob had mentioned the ease of use first that <unk>. Currently in second line just given the tolerability profile of the patient experience. The clinical activity. These patients that are coming in with <unk>.

Speaker Change: Second line small cell lung cancer generally have quite a poor health prognosis.

Speaker Change: 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 Thome with TD Cowen. Your line is open.

Operator: And we will take our next question from Joseph Thome with TB Cowen. Your line is open.

Joseph John: And we will take our next question from Joseph Tell me with TD Cowen Your line is open.

Joseph Thome: Hi there. Good evening. Congrats on the progress, and thank you for taking my question. Maybe just one on Zanidatamab. How should we think about continued investment in the program overall? I know you outlined the breast cancer opportunity and other HER2-expressing cancers.

Joseph Thome: Hi there. Good evening. Congrats on the progress, and thank you for taking my question. Maybe just one on zanidatamab. How should we think about continued investment in the program overall, and you outlined the breast cancer opportunity and other HER2 expressing cancers. I guess, what's sort of the decision point to make that additional investment to start additional studies, either in breast cancer or some of these other cancers? 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.

Joseph: In the program overall, I know you outlined the breast cancer opportunity and other her two expressing cancers.

Bruce Cozadd: I guess what's sort of the decision point to make that additional investment to start additional studies either in breast cancer or some of these other cancers? Is it the first kind of approval in BTC? If it works in GEA, or are you looking more at the landscape overall and competition? How should we think about the appetite to expand that? Thank you. Yeah. I'll start. And then, Renée or Rob, if you want to add anything in, you certainly can. While we don't give R&D guidance by program, you saw our R&D guidance for the full year represents about the same percentage of total revenues as we reported for 2023. With Zanidatamab having contributed a lot to the growth in R&D 2023 over 2022, we have a little bit more of an apples-to-apples comparison between 2023 and 2024.

Joseph Thome: I guess what's sort of the decision point to make that additional investment to start additional studies either in breast cancer or some of these other cancers? Is it the first kind of approval in BTC? If it works in GEA, or are you looking more at the landscape overall and competition? How should we think about the appetite to expand that? Thank you.

Speaker Change: What's sort of the decision point to make that additional investment to start additional studies either in breast cancer or some of these other cancers is it the first kind of approval and in BTC as it if it works and Gea, where are you looking more at the landscape overall on competition, how should we think about the appetite to expand that thank you.

Bruce C. Cozadd: 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&D guidance by program, you saw our R&D guidance for the full year represents about the same percentage of total revenues as we reported for 2023. With zanidatamab having contributed a lot to the growth in R&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 we'll certainly, at our R&D day in March be explaining a little bit more about our specific plans. But Rob, let me know if you want to say more now.

Bruce Cozadd: Yeah. I'll start. And then, Renée or Rob, if you want to add anything in, you certainly can. While we don't give R&D guidance by program, you saw our R&D guidance for the full year represents about the same percentage of total revenues as we reported for 2023. With Zanidatamab having contributed a lot to the growth in R&D 2023 over 2022, we have a little bit more of an apples-to-apples comparison between 2023 and 2024.

Speaker Change: Yeah, I'll start and then Renee Rob do you want to add anything in you certainly can.

Speaker Change: We don't give R&D guidance by program you saw our R&D guidance for the full year represents about the same percentage of total revenues as we reported for 2023.

Speaker Change: With zany data map, having contributed a lot to the growth in R&D.

Speaker Change: 23 over 2022.

Renee Gala: We have a little bit more of an apples to apples comparison between 2023 and 2024 I will say our guidance does assume act.

Bruce Cozadd: I will say our guidance does assume activity in breast as well as BTC and GEA. And we'll certainly, at our R&D day in March, be explaining a little bit more about our specific plans. But Rob, let me know if you want to say more now. Yeah. 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 settings. So we already have data. And as Bruce mentioned, we are planning for additional work in breast cancer even now. And we will take our next question from Gregory Renza with RBC Capital Markets. Your line is open. Hey. Good afternoon. Good evening, Bruce and team. Congrats on the progress, and thanks for taking my question.

Speaker Change: Activity in breast as well as.

Speaker Change: BTC and gea.

Speaker Change: And we will certainly at our R&D day in March be.

Speaker Change: Explaining a little bit more about our specific plans, but Rob let me know if you want to say more now.

Rob Iannone: Yeah. 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 settings. So we already have data. And as Bruce mentioned, we are planning for additional work in breast cancer even now.

Rob Iannone: Yes, only that we know, 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.

Rob: <unk> positive patients.

Rob: Early in metastatic setting so we already have data and as Bruce mentioned.

Rob: We are planning for additional work in breast cancer, even now.

Bruce Cozadd: And we will take our next question from Gregory Renza with RBC Capital Markets. Your line is open.

Operator: And we will take our next question from Gregory Renza from RBC Capital Markets. Your line is open.

Gregory Renza: Hey. Good afternoon. Good evening, Bruce and team. Congrats on the progress, and thanks for taking my question.

Gregory Renza: Hey, good afternoon, good evening, Bruce and team. And congrats on the progress and thanks for taking my question. Maybe, Bruce, just adding on to some of the color that you've provided around Vision ‘25 and that $500 million 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 just 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.

Bruce Cozadd: Maybe, Bruce, just adding on to some of the color that you've provided around Vision 25 and that $500 million 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 just 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 alleys. Thanks so much. Yeah. Greg, thanks for the question.

Gregory Renza: Maybe, Bruce, just adding on to some of the color that you've provided around Vision 25 and that $500 million 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 just 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 alleys. Thanks so much.

Gregory: Maybe Bruce just just adding on to some of the color that you've provided around vision 25 in that in that $500 million.

Gregory: Potentially through corporate development, just curious if you could comment a bit on where you see valuations for some of the areas in which Youre looking externally certainly 2023 as you noted maybe put 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.

Gregory: For attractiveness of.

Gregory: Assets that are in <unk>.

Speaker Change: <unk> power alleys. Thanks, so much.

Bruce Cozadd: Yeah. Greg, thanks for the question.

Bruce C. Cozadd: 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's 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 may be a little high to earn a good return. If that's true, that's why we look at other areas, as well, so with our team, with our strong financial position, we're confident we'll continue to find opportunities to put capital to work to drive that growth and sustainable growth over a longer period of time.

Bruce Cozadd: We have quite a bit of experience on the corporate dev side, having done a number of these transactions over the years, and feel like there's 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, add valuations that work for us. There can be pockets of areas where it seems like everyone's looking at the same time, and valuations may be a little high to earn a good return. If that's true, that's why we look at other areas as well.

Greg: We have quite a bit of experience some corp, Dev side, having done a number of these transactions over the years and feel like there is a great set of opportunities up there okay.

Speaker Change: Cross neuroscience and oncology as well as some rare disease spaces that would build on capabilities.

Speaker Change: We already have in house based on a lot of our activities over recent years.

Speaker Change: Being active in.

Speaker Change: All of those spaces looking at on market and near market.

Speaker Change: Products, including some in late stage development I think gives us.

Speaker Change: The ability to find things at valuations that worked for us.

Speaker Change: It can be pockets of.

Speaker Change: Of of areas, where it seems like everyone's looking at the same time evaluations.

Speaker Change: Maybe a little high to earn a good return if that's true.

Speaker Change: That's why we look at other areas as well so with our team with our strong financial position. We're confident we will continue to find opportunities to put capital to work to drive that growth and sustainable growth over a longer period of time.

Bruce Cozadd: 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. And we will take our next question from Annabel Samimy with Stifel. Your line is open. Hi. Thanks for taking my question. On Zanidatamab, 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, and could that potentially impact, say, Zepzelca? And then, I guess, sort of related, on the operating margin, Vision 2025, I guess, was supposed to be five points over where the guidance was set back in 2022.

Operator: And we will take our next question from Annabel Samimy with Stifel. Your line is open.

Speaker Change: And we will take our next question from Annabel <unk> with Stifel. Your line is open.

Annabel Samimy: Hi. Thanks for taking my question. On Zanidatamab, 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, and could that potentially impact, say, Zepzelca? And then, I guess, sort of related, on the operating margin, Vision 2025, I guess, was supposed to be five points over where the guidance was set back in 2022.

Annabel Samimy: Hi, thanks for taking my question. On zani, 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, which are type of investment you need to make in the launch of the infrastructure to appropriately target GEA cancers versus lung cancers, and could that potentially impact, say, ZEPZELCA? And then, I guess, sort of related, on the operating margin, Vision 2025, I guess, was supposed to be five 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 that you have to make here? Or just if you can give a little color there, that would be great. Thanks.

Annabel: Sandy I know that you're still in the rolling BLA process, but can you talk about your launch plans there or how you might be preparing for it in terms of sales what type of investment you need to make in the launch the infrastructure.

Annabel: To appropriately target Gi cancers versus lung cancers, and could that potentially impact say soccer.

Annabel: Then I guess sort of related.

Annabel: On the operating margin vision 2025, I guess it was supposed to be.

Annabel: Five points.

Annabel: Over where the guidance was set back in 2020, two I think you're still at 43 and that would've been 48. So.

Bruce Cozadd: 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. Thanks. Yeah. Annabel, maybe I'll take the second part of your question first, and then we'll come back to Zanidatamab commercial launch thinking. When we set that target, it was coming off of 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&D portfolio and behind our key growth drivers on the commercial side. So we're glad to be making those investments today.

Annabel Samimy: 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. Thanks.

Speaker Change: Are you backing off of that operating margin guidance given the number of investments that you have to make her or just if you can give a little color there that would be great. Thanks.

Bruce Cozadd: Yeah. Annabel, maybe I'll take the second part of your question first, and then we'll come back to Zanidatamab commercial launch thinking. When we set that target, it was coming off of 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&D portfolio and behind our key growth drivers on the commercial side. So we're glad to be making those investments today.

Bruce C. Cozadd: Yes. Annabel, maybe I'll take the second part of your question first, and then we'll come back to zanidatamab commercial launch thinking. When we set that target, it was coming off of 43% margin back in 2021. I'll point out we essentially achieve 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&D portfolio and behind our key growth drivers on the commercial side. 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. Renee, you want to talk about zanidatamab?

Speaker Change: Commercial launch thinking.

Speaker Change: When we set that target it was coming off of 43%.

Speaker Change: Margin back in 2021, I'll point out we essentially achieved.

Speaker Change: Achieve that increase in margin as we move through 2022, that's given us great flexibility to make the kinds of investments.

Speaker Change: I wanted to make in the R&D portfolio and behind our key growth drivers on the commercial side. So we're we're glad to be making those investments today, we obviously havent given guidance for 2025, specifically, yet I will point out as we've pointed out before that.

Bruce Cozadd: 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. Renée, you want to talk about zanidatamab? 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 Change: Whether or not we do a corporate development transaction and spread our expenses over a greater revenue base does impact our margins. So.

Speaker Change: We built that into our thinking as well, but for now we think the investments, we're making our investments that will lead to high return for our shareholders.

Speaker Change: Renee you want to talk about.

Renée Galá: 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.

Renee: Any data map.

Renee Gala: 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. It could happen as early as later this year, we'll be ready certainly, but but we're looking at more than likely 2025. So the way, we're thinking about the launches that we should be able to leverage our current. Field force that is out in the field right now with <unk> silica. With a relatively small augment to that field force. The key is to enter the market with BTC to help hcp's get important experience with Fannie data map. 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 HCP is getting experience with Danny it's a more seamless transition when you're thinking about gea also if we're looking at an S. BLA.

Renee Gala: Sure, yes, 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. 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 ZEPZELCA 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 zanidatamab. 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 zani, it's a more seamless transition when you're thinking about GEA.

Renee: It could happen as early as later this year, we'll be ready certainly, but but we're looking at more than likely 2025.

Bruce Cozadd: 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 Zepzelca 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 Zanidatamab. 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 Zanidatamab, it's a more seamless transition when you're thinking about GEA. 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 US. And we're also looking at Zanidatamab as a global brand, an important global brand for us.

Renée Galá: 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 Zepzelca 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 Zanidatamab. 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 Zanidatamab, it's a more seamless transition when you're thinking about GEA. 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 US.

Renee: So the way, we're thinking about the launches that we should be able to leverage our current.

Renee: Field force that is out in the field right now with <unk> silica.

Renee: With a relatively small augment to that field force. The key is to enter the market with BTC to help hcp's get important experience with Fannie data map.

Renee: 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 HCP is getting experience with Danny it's a more seamless transition when you're thinking about gea also if we're looking at an S. BLA.

Renee Gala: 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 zani as a global brand, an important global brand for us. So, after the U.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 need the U.S., Europe, and Japanese markets. And then as we expand into breasts, 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.

Renee: A process for GE, a that's of course, a bit faster as well.

Renee: So we think it's a relatively small expansion to the footprint in the U S. And we're also looking at Danny as a global brand an important global brand for us. So after the U S. We're also looking at Europe, as well as Japan, and while the BTC opportunity Holistically from an epidemiology.

Renée Galá: And we're also looking at Zanidatamab as a global brand, an important global brand for us.

Bruce Cozadd: So after the US, 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 US, Europe, and Japanese markets. 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. And we will take our next question from David Amsellem with Piper Sandler. Your line is open. Hey. Thanks. Can you talk a little more about Epidiolex and what drove the performance? Are you seeing double-digit volume growth, both US and ex-US?

Renée Galá: So after the US, 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 US, Europe, and Japanese markets. 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.

Renee: Perspective is smaller it's a high unmet need in terms of.

Renee: The severity of the cancer and so you know we're looking at a build strategy start with BTC, where we have around 12000 patients worldwide building to gea with 63000, and when I say worldwide I need the U S Europe and Japanese markets and then as we expand into breast we're looking at a much.

Renee: A larger population of more than 150000 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.

Renee: And we will take our next question from David and some of them with Piper Sandler Your line is open.

David Amsellem: Hey. Thanks. Can you talk a little more about Epidiolex and what drove the performance? Are you seeing double-digit volume growth, both US and ex-US?

David Amsellem: Hey, thanks. Can you talk a little more about EPIDIOLEX and what drove the performance? Are you seeing double digit volume growth, both U.S. and ex-U.S.? And was there any stocking benefit that we should be aware of? Thank you.

David: Hey, Thanks can you talk a little more about <unk>.

David: What drove the performance.

David: Is are you seeing double digit volume growth, both U S and ex U S and was there any stocking benefit that we should be aware of thank you.

Bruce Cozadd: Was there any stocking benefit that we should be aware of? Thank you. Thanks for the question, David. Renée, maybe I'll turn that one over to you. Sure. Yeah. Happy to comment. So as we look at Epidiolex, 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 a very small amount of that in Q4 in terms of buildup. But we are seeing continuing demand growth, and we're seeing that across both the US 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.

David Amsellem: Was there any stocking benefit that we should be aware of? Thank you.

Bruce Cozadd: Thanks for the question, David. Renée, maybe I'll turn that one over to you.

Bruce C. Cozadd: Thanks for the question, David. Renee, maybe I'll turn that one over to you.

Renée Galá: Sure. Yeah. Happy to comment. So as we look at Epidiolex, 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 a very small amount of that in Q4 in terms of buildup. But we are seeing continuing demand growth, and we're seeing that across both the US 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.

Renee Gala: Sure. Yes, happy to comment. So, as we look at EPIDIOLEX, 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 a very small amount of that in the fourth quarter in terms of buildup. But we are seeing continuing demand growth. And we're seeing that across both the U.S. as well as in Europe. We've said in the past what continues to resonate with physicians, providers, patient 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. 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.

Rene: So as we look at at the dialects as we've said in the past.

Rene: We tend to see a more gradual build up over the second half of the year and then that works off over the first half of the here because it's a very small amount of that in the fourth quarter in terms of build up.

Rene: But we are seeing continuing.

Rene: Demand growth and we're seeing that across both the U S as well as in Europe.

Rene: 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 were seeing with clubs and we see continued opportunity in the adult segment, that's an area.

Bruce Cozadd: 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. Then more broadly, as we look at how Epidiolex is viewed in the markets 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 polypharmacy with patients. We are seeing growth outside the US as well, as I'd mentioned.

Renée Galá: 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. Then more broadly, as we look at how Epidiolex is viewed in the markets 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 polypharmacy with patients. We are seeing growth outside the US as well, as I'd mentioned.

Piper Sandler: We're starting to focus a bit more on <unk>.

Piper Sandler: And that we expect to be a driver of growth in 2024.

Piper Sandler: And then more broadly as we look at how at the dialects as 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.

And then more broadly as we look at how at the dialects as 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

Renee Gala: 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 polypharmacy with patients. We are seeing growth outside the U.S. as well as I 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.

Piper Sandler: Generate both you know as I just described in terms of with club exam and the data beyond seizures and just further understanding of.

Piper Sandler: All of these effects that you're seeing is creating greater demand.

Piper Sandler: From our physician, stating they intend to use it earlier in their process.

Piper Sandler: Of this polypharmacy with patients we are seeing growth outside the U S. As well as I had 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.

Bruce Cozadd: 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. And we will take our next question from Joon Lee with Truist Securities. Your line is open. Great. Thanks for the update and for taking our questions. When you do report top-line data from Suvecaltamide and Essential Tremor, will you have a go-no-go decision when you report the 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 ORXN program. Thank you. Hey. So the first part of the question was around Essential Tremor.

Bruce Cozadd: 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.

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

Joon Lee: Great. Thanks for the update and for taking our questions. When you do report top-line data from Suvecaltamide and Essential Tremor, will you have a go-no-go decision when you report the 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 ORXN program. Thank you.

June Lee: Thanks for the update and for taking our questions. When you do report top line data from Suvecaltamide essential tremor, well, you have a go-no-go decision when you report a top line, or is that something that you still have to consult with the FDA in an end of Phase II 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 orexin program. Thank you.

Unknown Attendee: When you do report topline data from silver Kalsomine in essential tremor.

Unknown Attendee: Have a go no go.

Unknown Attendee: Go No go decision when you report the top line or is that something that you still have to consult with the FDA and the phase two meeting before being able to comment on a go no go no go decision and is the advancement into pockets at this disease dependent upon the outcome of it.

Unknown Attendee: Or are they independent events and just quickly anything you can share on the latest on your exit program. Thank you.

Bruce Cozadd: Hey. So the first part of the question was around Essential Tremor.

Bruce C. Cozadd: Okay, 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, it 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 interaction. Rob, anything else you want to add on ET or on orexin?

Bruce Cozadd: 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 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 interaction. Rob, anything else you want to add on ET or on ORXN? 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.

Unknown Attendee: Just share top line data on a timely basis, whether it'd be.

Unknown Attendee: Comment precisely the amount of time on next steps remains to be seen and remains to be.

Unknown Attendee: Depending on the data.

Unknown Attendee: In general our view is we know we need.

Unknown Attendee: To move this program forward, so I'm not sure.

Unknown Attendee: Barring a surprise in the data that would involve a different regulatory inner.

Unknown Attendee: Interaction, Rob anything else, you want to add on HC or an erection.

Rob Iannone: 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.

Rob Iannone: 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 action and a best in class calcium channel modulator. Certainly this trial was built to be part of a pivotal program, so I think it'll 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 and essential tremor would give us more confidence in this target overall. And then finally on the question of orexin, there are no updates there. We're on pause while we're examining the safety findings that we previously characterized.

Rob: With regard to ETE I agree with you that.

Rob: We will see the data and we're not expecting to have to talk to FDA before.

Rob: Driving some guidance on that it certainly is positioned as a pivotal trial, we're very excited about it given the high.

Rob: Unmet need there's there hasn't been an approved drug in 50 years and what's available Theres pretty poor. We think we have a differentiated mechanism of action and a best in class.

Bruce Cozadd: 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. Certainly, this trial was built to be part of a pivotal program, so I think it'll 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 ORXN, no updates there. We're on pause while we're examining the safety findings that we previously characterized. And we will take our next question from Gary Nachman with Raymond James. Your line is open. Hi. Good afternoon. So on Zanidatamab, what's the timeline for expanding further into breast cancer? Will you be doing that in parallel with BTC and GEA?

Rob Iannone: 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. Certainly, this trial was built to be part of a pivotal program, so I think it'll 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 ORXN, no updates there. We're on pause while we're examining the safety findings that we previously characterized.

Rob: Calcium channel modulator certainly this trial was built to be part of the pivotal program. So I think it will be quite informative when we do.

Rob: See the data.

Rob: I don't think PV Parkinson's disease tremor is a direct read through but certainly strong data in essential tremor would give us more confidence in this target.

Rob: Overall, and then finally on the on the question of Orexin No updates there we're on pause while we were examining the safety findings that we.

Rob: Previously characterized.

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

Gary Nachman: Hi. Good afternoon. So on Zanidatamab, what's the timeline for expanding further into breast cancer? Will you be doing that in parallel with BTC and GEA?

Gary Nachman: Hi, good afternoon. So on zani, just what's the timeline for expanding further into breast cancer? Will you be doing that in parallel with BTC 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 zani and not just BTC? Thank you.

Gary Jay Nachman: So on Sandy just what's the timeline for expanding further into breast cancer will you be doing that in parallel with BTC and gea and then regarding increasing the size of the Gea trial, just describe what you hope to see from that interim OS data.

Bruce Cozadd: 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 Zanidatamab and not just BTC? Thank you. Hey. Rob, I'm going to turn this one over to you. Yeah. 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. It's not dependent on any other readout.

Gary Nachman: 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 Zanidatamab and not just BTC? Thank you.

Speaker Change: And next year is it possible that gea could contribute to the sales as any.

Speaker Change: And not just BTC. Thank you.

Bruce Cozadd: Hey. Rob, I'm going to turn this one over to you.

Bruce C. Cozadd: Rob, I'm going to turn this one over to you.

Rob Iannone: Yeah. 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. It's not dependent on any other readout.

Rob Iannone: 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. 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 that it has no impact on the overall timeline.

Rob: And publishing on those data and we are progressing further development plans in those areas, it's not dependent on any other.

Speaker Change: Retail.

Bruce Cozadd: With regard to the changes to the GEA study, again, we made those changes to ensure better power for the final overall survival endpoint. We plan to read out the progression-free survival based on the original sample size so 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. 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.

Rob Iannone: With regard to the changes to the GEA study, again, we made those changes to ensure better power for the final overall survival endpoint. We plan to read out the progression-free survival based on the original sample size so 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. 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.

Speaker Change: With regard.

Speaker Change: Two the changes to the Gea study.

Speaker Change: Again, we made those changes.

Speaker Change: Ensure better power for the overall final overall survival.

Speaker Change: Endpoint.

Speaker Change: Plan to read out the progression free survival based on the original sample size.

Speaker Change: No impact on the overall timeline and we know from health authority interactions in this setting PFS is adequate.

No impact on the overall timeline

Rob Iannone: 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. 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 second 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, if this change. And then on the mature OS data, we'd have more power.

Speaker Change: To support approval, it's usually typical to do an interim analysis.

Speaker Change: Early.

Speaker Change: At the time that you are looking at PFS and generally health authorities just wanted to be sure that.

Speaker Change: Something funky is not happening that youre not seeing somehow a detriment in the OS, but there's not an expectation that OS on that first interim would.

Speaker Change: We'd be well powered and then of course, we have the.

Bruce Cozadd: Then, of course, we have the second 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 mature OS data, we'd have more power. And then with respect to. Yeah. I mean, in terms of, sorry, I didn't address the question on revenue in 2025. There's 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 US 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.

Rob Iannone: Then, of course, we have the second 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 mature OS data, we'd have more power. And then with respect to. Yeah. I mean, in terms of, sorry, I didn't address the question on revenue in 2025. There's 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 US 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.

Speaker Change: Second 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.

Speaker Change: On the mature OS data, we'd have more power.

Renee Gala: And then, with respect to -

Rob Iannone: I mean, in terms of -- sorry, I didn't get to the -- didn't address the question on revenue in 2025. There's 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.

Glenn: In a scenario, where we are given what we've shared around BTC that we are on the market.

Speaker Change: For BTC.

Speaker Change: And.

Speaker Change: As we read out the data for <unk>, we certainly have a faster path as a supplemental and the U S to get an update to the label, but we certainly will also publish.

Speaker Change: And seek.

Speaker Change: Companion listing.

Speaker Change: While we are progressing.

Speaker Change: The supplemental BLA.

Operator: And we will take our next question from Akash Tiwari with Jefferies. Your line is open.

Bruce Cozadd: We will take our next question from Akash Tewari with Jefferies. Your line is open. Hi. This is Eriane for Akash. Thanks for taking our question. Just a quick one on Zana in GEA. So given the mechanism similarity between Herceptin, Perjeta, combo, and Zana, why do you think their phase 3 GEA trial, JACOB, failed? It doesn't seem to be HER2 expression related given the treatment arm enrolled roughly similar HER2-3 population compared to the comparator arm, which is Herceptin plus chemo. So is there anything you are doing differently in your trial? Thanks. Rob, do you want to take that? Yeah. Yeah. Happy to, Bruce.

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

Speaker Change: And we will take our next question from <unk> <unk> with Jefferies. Your line is open.

Ariane van de Blaak: Hi. This is Eriane for Akash. Thanks for taking our question. Just a quick one on Zana in GEA. So given the mechanism similarity between Herceptin, Perjeta, combo, and Zana, why do you think their phase 3 GEA trial, JACOB, failed? It doesn't seem to be HER2 expression related given the treatment arm enrolled roughly similar HER2-3 population compared to the comparator arm, which is Herceptin plus chemo. So is there anything you are doing differently in your trial? Thanks.

Akash Tiwari: Hi, this is [inaudible] on for Akash. Thanks for taking our question. Just a quick one on zani in GEA. So, given the mechanism similarity between Herceptin Pergola combo and zani, why do you think their Phase III GEA trial, JACOB, failed? It doesn't seem to be like HER2 expression related, given the treatment arm enrolled roughly similar HER3 population compared to the comparator arm, which is Herceptin plus chemo. So, is there anything you are doing differently in your trial? Thanks.

Speaker Change: Treatment arm and road, roughly similar or two or three population compared to the comparator arm wishes Herceptin plus chemo. So is there anything youre doing interested only in red trial. Thanks.

Bruce Cozadd: Rob, do you want to take that?

Bruce C. Cozadd: Rob, you want to take that?

Rob Iannone: Yeah. Yeah. Happy to, Bruce.

Rob Iannone: Yes, happy to, Bruce. So first of all, while the epitopes on zanidatamab do correspond to the same epitopes that Herceptin and pergola independently bind. The reason zanidatamab is differentiated is that when they occur, when they're positioned on the same antibody, what you get is binding of the two FAB fragments of the antibody on different receptors. And it causes receptor clustering, which enhances interference of 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 with the bipartopic antibody and showing that it induces complement dependent incited toxicity, which is unique amongst any HER2 antibodies, and also some experimental data comparing head-to-head to just combining those two antibodies separately.

Bruce Cozadd: So first of all, while the epitopes on zanidatamab do correspond to the same epitopes that Herceptin and Perjeta independently bind, the reason zanidatamab is differentiated is that when they're positioned on the same antibody, what you get is binding of the two Fab fragments of the antibody on different receptors. And it causes receptor clustering, which enhances interference of 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 with the biparatopic 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 two antibodies separately.

Rob Iannone: So first of all, while the epitopes on zanidatamab do correspond to the same epitopes that Herceptin and Perjeta independently bind, the reason zanidatamab is differentiated is that when they're positioned on the same antibody, what you get is binding of the two Fab fragments of the antibody on different receptors. And it causes receptor clustering, which enhances interference of 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.

Rob: Consented data map do correspond to the same epitopes that herceptin and progenitor independently bind the reasons out of data Mab is differentiated.

Rob: When they occur when they are positioned on the same antibody. What you get is binding of the two F&B fragments of the antibody on different receptors and it causes receptor clustering, which enhances interference of signaling.

Rob: Whether that be through her two or interference with dimerization with her three and therefore, our interference is signaling with her three internalization.

Rob: And marking the cells for immune destruction.

Rob Iannone: A lot of this experimental data was published in Nature Communications and includes some really nice data showing this clustering effect that occurs with the biparatopic 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 two antibodies separately.

Rob: A lot of this experimental data was published in nature Communications and include some really nice data showing this clustering effect that occurs with the <unk> topic.

Rob: Antibody.

Rob: And showing that it induces complement dependent cytotoxicity, which is unique amongst any her two antibodies and also some experimental data comparing head to head to just combining those two antibodies separately.

Bruce Cozadd: So we think we actually have a differentiated drug that will be more effective than 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. 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. And we will take our next question from Charles Duncan with Cantor Fitzgerald. Your line is open. Hi. This is Asiya on for Charles. We have a question on Epidiolex.

Rob Iannone: So we think we actually have a differentiated drug that will be more effective than 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. 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.

Rob Iannone: So, we think we actually have a differentiated drug that will be more effective than 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 Pergola with breast cancer. 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, Pergola to BTC patients.

Rob: 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 <unk> with breast cancer. So I think our preclinical data show the differentiated mechanism and the clinical data.

Rob: Showing better results, whether it be in breast cancer or also in BTC, where we seem to have better results and when you give personnel to project out to PBC patients.

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

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

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

Asiya Reznikova: Hi. This is Asiya on for Charles. We have a question on Epidiolex.

Charles Duncan: Your line is open. Hi, this is Acia, on for Charles. We have a question on EPIDIOLEX. So given the Phase III 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 opportunity in the U.S? And also you did mention additional market launches this year so I was wondering if you can provide a bit more color on this? Thank you.

Bruce Cozadd: 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 opportunity in the US? And also, you did mention additional market launches this year, so I was wondering if you can provide a bit more color on this. Thank you. Yeah. Renée, let me turn that one over to you. Sure. Yeah. 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 three different indications that we think provide quite an important opportunity. And Japan, obviously, is the second-largest pharmaceutical market in the world. We have now the opportunity not only with Epidiolex but also Zanidatamab to be able to have meaningful opportunities in that market.

Asiya Reznikova: 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 opportunity in the US? And also, you did mention additional market launches this year, so I was wondering if you can provide a bit more color on this. Thank you.

Charles Duncan: Given the phase two read out 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. And also you did mention additional market launches. This year. So I was wondering if you can provide a bit more color on this thank you.

Bruce Cozadd: Yeah. Renée, let me turn that one over to you.

Bruce C. Cozadd: Yes, Renee, let me turn that one over to you.

Renée Galá: Sure. Yeah. 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 three different indications that we think provide quite an important opportunity.

Renee Gala: 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 three different indications that we think provide quite an important opportunity in Japan, obviously is the second largest pharmaceutical market in the world. We have now the opportunity, not only with EPIDIOLEX, but also zanidatamab 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.

Renee: That we think provide quite a bit.

Renee: An important opportunity in Japan, obviously is the second largest pharmaceutical market in the world. We have now the opportunity not only with at the dialects, but also is there any data on that to be able to have meaningful opportunities in that market.

Renée Galá: And Japan, obviously, is the second-largest pharmaceutical market in the world. We have now the opportunity not only with Epidiolex but also Zanidatamab to be able to have meaningful opportunities in that market.

Bruce Cozadd: 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 US, as we think about the progress that we're making there, we're already approved in more than 35 different countries. 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 five main large markets in Europe. So what we've been doing over the course of 2023 and 2024 is really focused on ensuring we have the full indication set available in each of the countries.

Renée Galá: 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 US, as we think about the progress that we're making there, we're already approved in more than 35 different countries. 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 five main large markets in Europe. So what we've been doing over the course of 2023 and 2024 is really focused on ensuring we have the full indication set available in each of the countries.

Renee: So we do expect the topline results in the second half of this year and we're pleased also with the progress we've made and to be able to see changes to the cannibal sorry.

Renee: Sorry, cannabis control act underway, which will enable that eventual launch.

Renee Gala: 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. 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 five main large markets in Europe. So, what we've been doing over the course of ‘23 and ‘24 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. And given we're now in a place where we're annualizing at more than $900 million, we see the product as being very much on track for blockbuster status.

Renee: 35 different countries, we do have some additional launches and reimbursement anticipated through the end of 2024 and I would think of that as you know graduate.

Renee: Gradual updates as we go we are already approved and reimbursed in the five main large markets in Europe. So what we've been doing over the course of 'twenty three and 24 is really focus on ensuring we have the full indication set available in each of the countries where.

Bruce Cozadd: 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. Given we're now in a place where we're annualizing at more than $900 million, we see the product as being very much on track for blockbuster status. We will take our next question from Jeff Hung with Morgan Stanley. Your line is open. 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 towards the switch to low sodium? Or do you think that the majority of the narcolepsy and IH community are more or less aligned with the benefits given the need for lifelong treatment?

Renée Galá: 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. Given we're now in a place where we're annualizing at more than $900 million, we see the product as being very much on track for blockbuster status.

Renee: Continuing to.

Renee: Be able to execute partnership agreements to ensure that either if we're not going direct were making the product available to our partners and we'll expect that to continue over the course of 'twenty 'twenty four and given we're now in a place where we're annualizing at more than $900 million, we see the.

Renee: <unk> is being very much on track for blockbuster status.

Renee: Yeah.

Operator: We will take our next question from Jeff Hung with Morgan Stanley. Your line is open.

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

Michael Riad: 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 towards the switch to low sodium? Or do you think that the majority of the narcolepsy and IH community are more or less aligned with the benefits given the need for lifelong treatment?

Jeff Hung: 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 towards the switch to low sodium? Or do you think that the majority of the narcolepsy and IH community are more or less aligned with the benefits, given the need for lifelong treatment? Thank you.

Michael Rehaut: On the high sodium authorized generic what evidence generation is needed to support the long term health messaging and drive patient like towards the switch to low sodium or do you think that the majority of the narcolepsy NIH community are more or less aligned with the benefits given the need for a lifelong treatment. Thank you.

Bruce Cozadd: Thank you. Yeah. I would say the evidence surrounding the impact of sodium on cardiovascular health is pretty incontrovertible and certainly underlay the original orphan drug exclusivity decision by FDA determining that Xywav was clinically superior to Xyrem on the basis of that lower sodium. The same thing could be said for Lumryz, 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 high-sodium oxybate therapy, we saw patients have a significantly increased either diagnosis of hypertension, or beginning antihypertensive meds.

Michael Riad: Thank you.

Bruce Cozadd: Yeah. I would say the evidence surrounding the impact of sodium on cardiovascular health is pretty incontrovertible and certainly underlay the original orphan drug exclusivity decision by FDA determining that Xywav was clinically superior to Xyrem on the basis of that lower sodium. The same thing could be said for Lumryz, 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 high-sodium oxybate therapy, we saw patients have a significantly increased either diagnosis of hypertension, or beginning antihypertensive meds.

Bruce C. Cozadd: Yes, I would say the evidence surrounding the impact of sodium on cardiovascular health is pretty incontrovertible. I certainly underlined the original Orphan Drug Exclusivity Decision by FDA determining that XYWAV was clinically superior to XYREM on the basis of that lower sodium and the same thing could be said for LUMRYZ which has the same sodium level as XYREM. That 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 high sodium oxybate therapy, we saw patients have a significantly increased either diagnosis of hypertension or getting antihypertensive med. So, even in a short period of time, you see that impact on people, even if they aren't already diagnosed as being hypertension patients, which is again why that original determination was that XYWAV would be a safer product in all narcolepsy patients, who are known to be at high cardiovascular risk to begin with.

Renee: Certainly.

Renee: The original orphan drug exclusivity decision by FDA.

Renee: Determining that sideways was clinically superior to xyrem on the basis of that lower sodium.

Renee: The same thing could be said for loom rise, which has the same sodium level of xyrem doesn't mean, there aren't opportunities bring out more data as we have already.

Renee: Including with our presentation at the neurology meeting last year.

Renee: That within a period of 180 days of skirting.

Renee: Sodium <unk> therapy, we saw patients.

Renee: Significantly increased.

Renee:

Renee: Either diagnosis of hypertension or beginning anti hypertensive.

Bruce Cozadd: 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 Xywav would be a safer product in all narcolepsy patients who are known to be at high cardiovascular risk to begin with. We will take our next question from Joel Beatty with Baird. Your line is open. Hi. Thanks for taking the question. For Zanidatamab, how much of the $2 billion 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 I-SPY 2 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.

Renee: So even in a short period of time, you see that impact on people, even if they aren't.

Renee: Already diagnosed as being hypertensive patients, which is again why it had original determination was that.

Renee: Wave 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.

Operator: We will take our next question from Joel Beatty with Baird. Your line is open.

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

Joel Beatty: Hi. Thanks for taking the question. For Zanidatamab, how much of the $2 billion 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 I-SPY 2 and MD Anderson collaboration trials?

Joel Beatty: Hi, thanks for taking the question. For zanidatamab, how much of the $2 billion 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 I-SPY2 and MD Anderson collaboration trials?

Joel Beatty: Are you able to give a sense of when we might see data in that setting from the I spy, two and MD Anderson collaboration trials.

Bruce Cozadd: I'll take the first part of that, and then, Rob, hand the data part of it over to you.

Bruce C. Cozadd: I'll take the first part of that and Rob and the data part of it over to you we have not provided a breakdown. The opportunity set for us. <unk>, which we believe is extensive and certainly in our slides you can see that while we have made the most commentary thus far on DTC and gea and breast cancer. It's certainly has potential beyond those. Indications as well, which is why we say north of $2 billion, 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. Work out and looking forward to sharing a little more information. At our R&D day, but on timing of data, Rob maybe I'll turn that one over to you. Yes for the MD Anderson Neo Adjuvant study some data already published you may be aware of that December at the San Antonio. While is ongoing and I would expect some updates happen they haven't indicated exactly when the updates that we published. And I spy, which is a little bit. Ladies I started a little bit after that trial really depends on the.

Bruce C. Cozadd: I'll take the first part of that and Rob, hand the data part of it over to you. We have not provided a breakdown of the opportunity set for zanidatamab which we believe is extensive 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 billion, 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 work out and looking forward to sharing a little more information at our R&D day. But on timing of data, Rob, maybe I'll turn that one over to you.

Bruce Cozadd: We have not provided a breakdown of the opportunity set for zanidatamab, which we believe is extensive. 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're saying north of $2 billion. 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&D day. On timing of data, Rob, maybe I'll turn that one over to you. Yeah. 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.

Speaker Change: The opportunity set for us.

Rob: <unk>, which we believe is extensive and certainly in our slides you can see that while we have made the most commentary thus far on DTC and gea and breast cancer. It's certainly has potential beyond those.

Rob: Indications as well, which is why we say north of $2 billion, 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.

Rob: Work out and looking forward to sharing a little more information.

Rob: At our R&D day, but on timing of data, Rob maybe I'll turn that one over to you.

Rob Iannone: Yeah. 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.

Rob: Yes for the MD Anderson Neo Adjuvant study some data already published you may be aware of that December at the San Antonio.

Rob Iannone: 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. On I-SPY, which is a little bit late, it started a 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 zani is particularly well positioned to provide a better tolerated option for women with curative breast cancer.

Rob: While is ongoing and I would expect some updates happen they haven't indicated exactly when the updates that we published.

Bruce Cozadd: They haven't indicated exactly when the updates will be published. On I-SPY 2, which is a little bit late, it has started a little bit after that trial. It really depends on the enrollment rate, 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 Zana is particularly well-positioned to provide a better-tolerated option for women with curative breast cancer. And ladies and gentlemen, we have no further questions at this time. I will now turn the call back to Mr. Bruce Cozadd for closing remarks. Thank you, operator.

Rob Iannone: They haven't indicated exactly when the updates will be published. On I-SPY 2, which is a little bit late, it has started a little bit after that trial. It really depends on the enrollment rate, 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 Zana is particularly well-positioned to provide a better-tolerated option for women with curative breast cancer.

Speaker Change: And I spy, which is a little bit.

Speaker Change: Ladies I started a little bit after that trial really depends on the.

Speaker Change: The enrollment rate and the results when that might graduate from that phase and so we don't have any specifics at this point, but we are pleased.

Rob: Trials are ongoing and we're excited to see how that may inform.

Rob: Next steps in that early stage.

Rob: So we think as Andy is particularly well positioned to provide.

Rob: Better tolerated option for women with curative.

Rob: 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 Cozadd for closing remarks.

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

Bruce Cozadd: Thank you, operator.

Bruce C. Cozadd: 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.

Bruce Cozadd: 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. Ladies and gentlemen, this concludes today's call, and we thank you for your participation. You may now disconnect.

Bruce: 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.

Speaker Change: You all for joining us today.

Operator: Ladies and gentlemen, this concludes today's call, and we thank you for your participation. You may now disconnect.

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

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

Speaker Change: [music].

Speaker Change: Yes.

Speaker Change: [music].

Rob: Sure.

Rob: [music].

Q4 2023 Jazz Pharmaceuticals plc Earnings Call

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