Q3 2023 Jazz Pharmaceuticals PLC Earnings Call

Speaker 1: Good afternoon, my name is Christa, and I'll be your conference operator today. At this time, I would like to welcome everyone to the Jazz Pharmaceuticals 3rd quarter, 2023 earnings call. All lions 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 star followed by the number one on your telephone keypad. And if you would like to withdraw your question, again, press star one.

Good afternoon, My name is Krista and I'll be your conference operator today at this time I would like to welcome everyone to the jazz Pharmaceuticals third quarter 2023 earnings call. All lines have been placed on mute to prevent any background noise. 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 star followed by the number one on your telephone keypad and if you would like to withdraw your question again press Star one.

Speaker 1: Thank you. I would now like to turn the conference over to Andrea Flynn, Vice President, head of the minister relations. You may begin.

Thank you I would now like to turn the conference over to Andrea Flynn Vice President head of the DAU Relations you may begin.

Speaker 2: Thank you, Operator, and good afternoon, everyone. Today, Judge Pharmaceuticals reported its third quarter of 2023 financial results. The slide presentation accompanying this webcast is available on the Investor's 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, our Bruce Khozad, chairman and chief executive officer, Renee Gala, president and chief operating officer, and Rob Yunoan, executive vice president, global head of R&D.

Thank you operator, and good afternoon, everyone today Jazz Pharmaceuticals reported its third quarter 2023 financial results. The slide presentation accompanying this webcast is available on the investors section of our web site 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 <unk>, Chairman and Chief Executive Officer, Renee Gala, President and Chief operating Officer, and Rob You know executive Vice President Global head of R&D.

Speaker 2: Kim Stablech, Executive Vice President and General Manager, United States, will join the team for Q&A.

Jim <unk> Executive Vice President and General manager, United States will join the team for Q&A.

Speaker 2: On slide two, I'd like to remind you that today's webcast includes so-called 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 risk limits or entities that could cause actual events, performance and results to different materially from those contained in these so-called looking statements.

On slide two I'd like to remind you that today's webcast include forward looking statements such as those related to our future financial and operating results 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 forward looking statements.

Speaker 2: We encourage you to review the statements contained in today's press release, in our slide deck, and in our latest SCC disclosure documents, 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 encourage you to review the statements contained in today's press release in our slide deck and in our latest SEC disclosure documents, 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.

Speaker 2: We undertake no due to your obligation to update our forward looking statement.

Speaker 2: Turning to slide three on this webcast, we'll discuss non-GAAP financial measures. 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.

Turning to slide three on this webcast, we'll discuss non-GAAP financial measures descriptions of these non-GAAP financial measures and reconciliations of GAAP to non-GAAP financial measures are included in today's press release and the slide presentation available on the investors section of our website.

I'll now turn the call over to Bruce.

Speaker 3: Thanks Andrea. Good afternoon everyone and thank you for joining us today. I'll start on slide 5 in the 3rd quarter of 2023. We delivered strong commercial results, advanced multiple late stage programs within our pipeline. And maintain our focus on driving operational excellence.

Thanks, Andrea good afternoon, everyone and thank you for joining us today I'll start on slide five in the third quarter of 2023, we delivered strong commercial results.

Amps multiple late stage programs within our pipeline and maintain our focus on driving operational excellence our results for the quarter exemplify. The successful execution that has led to an exciting transformation and diversification of our business across our commercial portfolio and R&D pipeline and we remain well.

Speaker 3: Our results for the quarter exemplify the successful execution that has led to an exciting transformation and diversification of our business across our commercial portfolio and R&D pipeline, and we remain well positioned to achieve Vision 2025.

Positioned to achieve vision 2025.

Speaker 3: As we highlighted in today's press release, we've updated our 2023 guidance, raising our full year total revenue and oncology revenue guidance at the mid-

As we highlighted in today's press release, we've updated our 2023 guidance raising our full year total revenue and oncology revenue guidance at the midpoint.

Speaker 3: And as our pipeline continues to advance, we are increasing our R&D guidance, primarily driven by investments in Zany Data Map development across multiple her two expressing camps.

Our pipeline continues to advance we are increasing our R&D guidance, primarily driven by investments in Sandy data map development across multiple her two expressing cancers that we believe will allow us to deliver an important new therapeutic option with the potential to raise the standard of care for patients and create long term value.

Speaker 3: that we believe will allow us to deliver an important new therapeutic option with the potential to raise the standard of care for patients and create long-term value for jobs.

For jazz.

Speaker 3: It's important to note that our disciplined approach to capital allocation has allowed us to invest in R&D as well as key commercial friends.

It is important to note that our disciplined approach to capital allocation has allowed us to invest in R&D as well as key commercial franchises, while remaining on track to deliver on our full year GAAP net income and non-GAAP adjusted net income guidance.

With regard to our commercial business, we are seeing strong momentum across all three key growth drivers sideways at the dialogues and railways.

Speaker 3: With regard to our commercial business, we are seeing strong momentum across all three key growth drivers, Zywave, Epidilex, and Rylade.

Speaker 3: Combined, revenue from these products grew 24% in the third quarter compared to the same period last year.

Combined revenue from these products grew 24% in the third quarter compared to the same period last year.

Speaker 3: We remain confident in the durability of our oxalate franchise and the growth of Zae wave in both narcolepsy and adiopathic hypersomnia or IH. Even as high sodium branded and authorized neuro competition has entered the narcolepsy mark.

We remain confident in the durability of our Oxidate franchise and the growth of XI wave in both narcolepsy and idiopathic hypersomnia, where IH, even as high sodium branded and authorized generic competition has entered the narcolepsy market.

Speaker 3: SiWave is annualizing at $1.3 billion in revenue, remains the oxidative choice, and is the only approved treatment for IA.

So I wave is annualizing at $1 $3 billion in revenue remains the oximeter choice and is the only approved treatment for IH underlying demand continues to drive up the dialects growth we remain confident in its potential to reach blockbuster status and contribute more than $1 billion in revenue to our vision 2020.

Speaker 3: Underlying demand continues to drive up a dialect's growth. We remain confident in its potential to reach blockbuster status and contribute more than a billion dollars in revenue to our Vision 2025 revenue target. Outside the U.S., we expect additional launches and indication expanses through 2024.

<unk> revenue targets outside the U S. We expect additional launches and indication expansion through 2024.

Speaker 3: In oncology, Ryleys has continued to grow in the US, supported by strong demand from pediatric patients, and our increasing emphasis on the adolescent and young adult marks.

In oncology <unk> continued to grow in the U S supported by strong demand for pediatric patients and our increasing emphasis on the adolescent and young adult market in.

Speaker 3: In addition, we recently received marketing authorization for the product in Europe under the trade name and Riley.

In addition, we recently received marketing authorization for the product in Europe under the trade name and release.

Speaker 3: The performance of these products together with Zepp Delca revenues is fueling the ongoing diversification of our commercial business.

The performance of these products together was up soccer revenues is fueling the ongoing diversification of our commercial business.

Speaker 3: More than half of net product revenue this quarter came from FDILX and or oncology products combined.

More than half of net product revenue this quarter came from a map of dialects and our oncology products combined.

Speaker 3: and Xi Wave represented more than two thirds of our oxabay.

XI wave represented more than two thirds of <unk> revenue.

Speaker 3: This marks a significant shift from just a few years ago when Zayrem represented three quarters of total rip.

This marks a significant shift from just a few years ago. When ziram represented three quarters of total revenue.

This diversified revenue stream is a direct result of our outstanding commercial execution, along with successful corporate development and internal R&D efforts moving to our pipeline. We now expect up to five late stage Readouts through the end of 2020 for Rob will cover our R&D progress in more detail later in the call.

Speaker 3: This diversified revenue stream is a direct result of our outstanding commercial execution along with successful corporate development and internal R&DF.

Speaker 3: Moving to our pipeline, we now expect up to five late-stage readouts through the end of 2024. Rob will cover our R&D progress in more detail later in the call. But I want to highlight that we've used any data map as the most de-risk and highest priority program in our...

But I want to highlight that we view as any data map is the most de risked and highest priority program in our pipeline.

Speaker 3: We plan to initiate a Rolling Biologics License Application or BLA submission this year for Accelerated Approval of his anti-data map for second line treatment of Biliary Track Cancer or BTC.

We plan to initiate a rolling biologics license application or BLA submission this year for accelerated approval or as Andy data Mab for second line treatment of biliary tract cancers or BTC.

Speaker 3: This is an important step in delivering Xanny DataMap to patients with BTC and other HER2-expressing cancers with limited treatment options.

This is an important step in delivering zany data map to patients with BTC and other her two expressing cancers with limited treatment options.

Speaker 3: given the strength of clinical data today and its promise in multiple indications. We believe Zannie has the potential to deliver more than $2 billion in peak revenue.

Given the strength of clinical data to date and its promise in multiple indications. We believe as Andy has the potential to deliver more than $2 billion in peak revenues.

Speaker 3: On the operational front, our commercial execution, along with attention to operational excellence, has put us in strong place.

On the operational front, our commercial execution, along with attention to operational excellence has put us in strong financial position.

We continue to generate significant cash flow from operations, which combined with our strong balance sheet gives us the capacity to invest in the products pipeline programs and corporate development opportunities with the highest potential to deliver sustainable growth and enhance value.

Speaker 3: We continue to generate significant cash flow from operations, which combined with our strong balance sheet gives us the capacity to invest in the products, pipeline programs and corporate development opportunities with the highest potential to deliver sustainable growth and enhanced value.

Speaker 3: Turning to slide six, we are very pleased with our progress in the third quarter and believe it has advanced us toward achieving all three components of Vision 2025 as we continue our transformation into a high growth global biopharma leader.

Turning to slide six we are very pleased with our progress in the third quarter and believe it has advanced us toward achieving all three components of vision 2025, as we continue our transformation into a high growth global Biopharma leader.

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 will provide a financial overview and then we'll open the call to Q&A.

Speaker 3: 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?

Hey.

Thanks, Bruce it's been an exciting few weeks says I'd assume my new role and while I'm working across the different part of the organization My focus remains sustained.

Speaker 2: Thanks, Bruce. It's been an exciting few weeks as I've assumed my new role. And while I'm working across a different part of the organization, my focus remains the same.

Driving that continued growth and transformation of our business starting on slide eight our confidence in the durability of our Oxidate franchise has only increased as we gain more visibility into how market dynamics are evolving with the availability of branded and AG high sodium oxalate.

Speaker 2: driving the continued growth and transformation of our business. Starting on slide eight, our confidence in the durability of our Oxabate franchise has only increased as we gain more visibility into how market dynamics are evolving with the availability of branded and AG high-sodium Oxabate.

Total Oxidate revenue, which includes XI wavelength xyrem revenues together with royalties from Xyrem authorized generics is annualizing at $1.9 billion and we are well positioned to achieve our stated goal of $2 billion in Oxidate revenues as part of vision 2025.

Speaker 4: Total Oxebit Revenue, which includes Zywave and Zyram revenues together with royalties from Zyram authorized generics, is annualizing at $1.9 billion, and we are well positioned to achieve our stated goal of $2 billion in Oxebit Revenue as part of Vision 2025.

<unk> revenue was approximately $332 million for the third quarter of 2023, representing growth of 30% compared to the same period in 2022, driven by continued adoption in both narcolepsy and I H.

Speaker 4: Xywave revenue was approximately $332 million for the third quarter of 2023, representing growth of 30% compared to the same period in 2022, driven by continued adoption in both narcolepsy and IH.

Speaker 4: Exiting the third quarter, there were approximately 9,500 narcolepsy patients taking ZyWave. Our focus on educating patients and prescribers about the benefits of reducing sodium intake continues to drive growth. And we recently launched a new campaign to support these initiatives.

Exiting the third quarter, there were approximately 9500 narcolepsy patients, taking sideways or focus on educating patients and prescribers about the benefits of reducing sodium intake continues to drive growth and we recently launched a new campaign to support these.

It is importantly.

Speaker 4: Importantly, we are seeing adoption from both high-sodium oxibates and oxibate-naive patients.

Importantly, we are seeing adoption from both high sodium ox abates and oxo beat naive patients.

Speaker 4: In IH, we see continued growth of new prescribers, and exiting the third quarter, there were approximately 2,550 active IH patients on Zyways.

I H, we see continued growth of new prescribers and exiting the third quarter. There were approximately 2550 active IH patients on valuation.

Speaker 4: Zaiway is uniquely positioned to address the multiple symptoms of IH, including sleep inertia, excessive daytime sleepiness, and cognitive impairment, all of which had a significant impact on patients' quality of life and daily function.

<unk> is uniquely positioned to address the multiple symptoms of IH, including sweep inertia excessive daytime sleepiness and cognitive impairment all of which had a significant impact on patients quality of life and daily function.

Based on the opportunity to improve the lives of people living with I H and our confidence that the IH indication represents a durable growth driver for XI wave, we are increasing our investment to further build the market. This will include educational initiatives and expanding our field team to include.

Speaker 4: Based on the opportunity to improve the lives of people living with IH and our confidence that the IH indication represents a durable growth driver for ZyWave, we are increasing our investment to further build the market. This will include educational initiatives and expanding our field team to include members specifically focused on IH to increase the breadth of prescribers.

<unk> members, specifically focused on the IH to increase the breadth of prescribers.

Speaker 4: Slide nine highlights our latest educational campaign for narcolepsy treaters, Less is More, which reinforces the compelling low-sodium health benefits of Ziways.

Slide nine highlights our latest educational campaign for narcolepsy treaters less is more which reinforces the compelling low sodium health benefits of die wave.

Speaker 4: Narcolepsy is a debilitating chronic condition and we have focused our educational efforts around the lifelong burden of high sodium intake for narcolepsy patients who live with a two to three times higher risk than the general population of cardiovascular comorbidities such as stroke and heart failure.

Narcolepsy is a debilitating chronic condition and we have focused our educational efforts around the lifelong burden of high sodium intake for narcolepsy patients who live with a two to three times higher risk than the general population of cardiovascular comorbidities, such as stroke and heart failure.

Speaker 4: XiWave is the only approved low-sodium oxivate containing 92% less sodium than high-sodium oxivates, and importantly, is the only oxivate without a labeled warning about high-sodium intake.

Z wave is the only approved to low sodium oxidate containing 92% less sodium than high sodium oxalates and importantly is the only oxidate without a labeled warning about high sodium intake.

You've heard us use a number of comparisons for the sodium load of high sodium oxidate versus highways, including eating for large orders of fast food French fries or five large bags of potato chips every night before bad.

Speaker 4: You've heard us use a number of comparisons for the sodium load of high-sodium oxalate versus Zywave, including eating four large orders of fast-food French fries or five large bags of potato chips every night before bed, or that it would take 12 years of treatment with Zywave to equal the sodium intake of one year of high-sodium oxalate treatment.

Or that it would take 12 years of treatment with sideways to equal the sodium intake.

One year of high sodium ox abate treatment.

Regardless of the parallels we draw the bottom line is clear the sodium reduction offered by XI wave has significant potential health benefits, including lower blood pressure and improves cardiovascular health.

Speaker 4: Regardless of the parallels we draw, the bottom line is clear. The sodium reduction offered by ZiWave has significant potential health benefits, including lower blood pressure and improved cardiovascular health.

We recently presented data at the World sleep meeting that builds on our body of research demonstrating the clear relationship between sleep disorders and increased cardiovascular risk.

Speaker 4: We recently presented data at the World Sleep Meeting that built on our body of research demonstrating the clear relationship between sleep disorders and increased cardiovascular risk.

Speaker 4: as well as the meaningful improvements possible with treatment plans that consider a patient's holistic health, such as reducing sodium intake.

As well as the meaningful improvements possible with treatment plans that consider a patient's holistic health such as reducing sodium intake.

Speaker 4: And earlier this year, we shared data at the American Academy of Neurology meeting that showed narcolepsy patients treated with high sodium oxalate had a higher risk of new onset hypertension diagnosis or antihypertensive medication initiation within 180 days of starting therapy when compared to a matched control group of narcolepsy patients not being treated with high sodium oxalate.

And earlier this year, we shared data at the American Academy of Neurology meeting that showed narcolepsy patients treated with high sodium oxidate had a higher risk of new onset hypertension diagnosis or anti hypertensive medication initiation within 180 days of starting <unk>.

Europe's <unk> when compared to a matched control group of narcolepsy patients not being treated with high sodium oxalate.

Speaker 4: The risk of those taking high-sodium oxidate was approximately twice that of the control group.

The risk of those taking high sodium oxidate.

Was approximately twice that of the control group.

We believe that the majority of patients and health care providers will continue to prioritize long term health when evaluating oxidate therapy, and we are finding the direct competitive messaging in the less is more campaign to be effective.

Speaker 4: We believe that the majority of patients and healthcare providers will continue to prioritize long-term health when evaluating Oxybate therapy, and we are finding the direct competitive messaging in the less is more campaign to be effective.

Speaker 4: Additionally, since we know this disease and its treatment are complex, the campaign also highlights the advantages of individualized dosing regimens for ZY wave patients and the support services that Jazz makes available for HCPs and their office staff to have ZY wave prescriptions approved, reimbursed, and delivered to patients.

Additionally, since we know this disease and its treatment are complex. The campaign also highlights the advantages of individualized dosing regimens for sideways patience and the support services. The jazz makes available for H C piece and their office staff to have XI wave prescriptions approved reimbursed.

And delivered to patients.

Speaker 4: We also offer a range of patient services that include copay assistance and disease education.

We also offer a range of patient services that include co pay assistance and disease education.

Turning to slide 10, and at the dialects, we achieved another quarter of growth with net product sales, increasing 9% year over year to approximately $214 million driven by underlying demand in both our U S and European markets.

Speaker 4: Turning to slide 10 in Epidiolex, we achieved another quarter of growth with net product sales increasing 9% year over year to approximately $214 million driven by underlying demand in both our US and European markets.

Speaker 4: Key drivers of this demand growth include Epidiolex's strong product profile, including data around benefits beyond seizure control, increased penetration in the long-term care setting, and strong uptake in key European markets, all of which provide us with continued confidence in the blockbuster potential of the product.

Key drivers of this demand growth include at the dialects as strong product profile, including data around benefits beyond seizure control increased penetration in the long term care setting and strong uptake in key European markets, all of which provide us with continued confidence in them.

Blockbuster potential of the product.

Turning to slide 11, we are focused on multiple opportunities to drive out the dialects to blockbuster status, including continued data generation and we expect 2% several dataset at the upcoming American Epilepsy Society meeting in December.

Speaker 4: Turning to slide 11, we are focused on multiple opportunities to drive epidiolex to blockbuster status, including continued data generation. And we expect to present several data sets at the upcoming American Epilepsy Society meeting in December .

Speaker 4: Our educational efforts around caregiver-reported outcomes beyond seizure control from the BECOME survey have been especially impactful.

Our educational efforts around caregiver reported outcomes beyond seizure control from the become survey had been especially impactful further differentiating at the dialects from other anti seizure medicines.

Speaker 4: further differentiating epidemiologists from other anti-seizure medicines.

Speaker 4: To accompany this caregiver reported data on improvements in cognition, behavior, and other non seizure benefits and LGS and DS, we have initiated the post marketing epicom trial in TSC.

To accompany this caregiver reported data on improvements in cognition behavior and other non seizure benefits in lgs and D. S. We have initiated the post marketing epic Com trial in T. S C.

Speaker 4: Epicom was designed in collaboration with HCPs and patient advisory groups to evaluate the impact of Epidiolex on behavioral and cognitive functioning and outcomes using a range of validated scales.

<unk> was designed in collaboration with Hcp's and patient advisory groups to evaluate the impact of that the dialects on behavioral and cognitive functioning and outcomes using a range of validated scales.

Speaker 4: Our commercial team also has an enhanced focus on dosing optimization, further penetration in the adult setting, and continued growth outside the U.S.

Our commercial team also has an enhanced focus on dosing optimization further penetration in the adult setting and continued growth outside the U S.

Turning to slide 12, and our oncology franchise net product sales for <unk> were approximately $105 million for the third quarter, a 43% increase year over year.

Speaker 4: Turning to slide 12 and our oncology franchise, net product sales for Rylase were approximately $105 million for the third quarter, a 43% increase year over year.

Speaker 4: Demand for Riley's remains strong, and we see a number of factors that are driving what we believe is sustainable growth.

Demand for Riley remains strong and we see a number of factors that are driving what we believe is sustainable growth.

Speaker 4: First, healthcare providers have indicated that they are returning to best clinical practice and switching therapy at the first signs of hypersensitivity, which was often not possible under the supply limitations with Erwin A.

First health care providers have indicated that they are returning to best clinical practice and switching therapy at the first signs of hypersensitivity.

It was often not possible under the supply limitations with <unk>.

Speaker 4: Second, while Rylase has been almost universally adopted in pediatric oncology protocols, we are now also seeing increased pediatric usage in several other areas.

Second well release has been almost universally adopted in pediatric oncology protocols. We are now also seeing increased pediatric usage in several other areas. These areas include physicians switching patients from E. Coli based asparaginase due to other treatment related issues that arise.

Speaker 4: These areas include physicians switching patients from E. coli-based asparaginase due to other treatment-related issues that arise.

As well as some use of <unk> in first line treatment based on its advantages of having a short acting profile relative to current first line of spirit <unk> therapies.

Speaker 4: as well as some use of Rilase in first-line treatment based on its advantages of having a short-acting profile relative to current first-line asparaginase therapies.

Speaker 4: Third, we continue to see increased adoption of the Monday, Wednesday, Friday, 25, 25, 50 milligrams per meter squared dosing, which is more in line with preferred clinical practice and allows for a dosing schedule that ensures sustained asparaginase levels through the course of treatment, which is essential to improved outcomes for patients.

Third we continue to see increased adoption of the Monday Wednesday, Friday, 25, 25, 50 milligrams per meter squared dosing, which is more in line with preferred clinical practice and allows for a dosing schedule that ensure sustained asparaginase levels through the course of treatment.

Which is essential to improved outcomes for patients.

Speaker 4: Fourth, we are seeing increased use of Rylase in the treatment of adolescents and young adults or the AYA market, and we expect continued growth in this segment.

Fourth we are seeing increased use of <unk> in the treatment of adolescents and young adults or the a Y a market.

We expect continued growth in this segment our field teams have been expanding our educational efforts to a way a treaters this year with a focus on physicians, who have previously used asparaginase therapy.

Speaker 4: Our field teams have been expanding their educational efforts to AYA treaters this year with a focus on physicians who have previously used asparagus and astherapy.

Outside the U S. We recently received European Commission approval under the trade name in Rye lease and are planning to begin a rolling launch later this year.

Speaker 4: Outside the US, we recently received European Commission approval under the trade name in Ryleis, and are planning to begin a rolling launch later this year. With respect to the market opportunity, the commercial landscape in Europe has a number of differences compared to the US, including competition and market access dynamics.

With respect to the market opportunity the commercial landscape in Europe has a number of differences compared to the U S, including competition and market access dynamics.

Speaker 4: Turning to slide 13, Zetzelka remains the treatment of choice in second-line small cell lung cancer and has generated more than $800 million in revenue since launch, proving to be a highly creative and well-executed corporate development transaction for jazz.

Turning to slide 13 that Cellcom remains the treatment of choice in second line small cell lung cancer and has generated more than $800 million in revenue since launch proving to be a highly accretive and well executed corporate development transaction for jazz.

Speaker 4: Net product sales for the third quarter increased 11% year over year to $78 million driven by an increase in underlying demand.

Net product sales for the third quarter increased 11% year over year to $78 million driven by an increase in underlying demand.

Speaker 4: A portion of this demand relates to the continued shortage of platinum chemotherapy, which has led to oncologists choosing Zepselka for some patients they may have historically re-challenged with platinum therapy. Although this dynamic may be temporary in nature, it is currently resulting in greater use of Zepselka, particularly in the community setting where its clinical profile and ease of administration have been well received.

A portion of this demand relates to the continued shortage of platinum chemotherapy, which has led to oncologists choosing that cellcom for some patients. They may have historically re challenged with platinum therapy.

Although this dynamic may be temporary in nature. It is currently resulting in greater use of <unk>, particularly in the community setting where its clinical profile and ease of administration have been well received.

While we have achieved significant penetration in the second line setting there remains an important unmet need for patients diagnosed with small cell lung cancer.

Speaker 4: While we have achieved significant penetration in the second line setting, there remains an important unmet need for patients diagnosed with small cell lung cancer. We expect top-line PFS data from our pivotal phase three trial of Zepselka in combination with dysentric and first-line small cell lung cancer at the end of 2024 or early 2025.

We expect top line PFS data from our pivotal phase III trial of <unk> in combination with to centric in first line small cell lung cancer at the end of 'twenty 'twenty four or early 2025.

Speaker 4: A positive outcome in this trial would provide a further opportunity to both improve patient lives and outcomes, as well as drive future growth in our oncology franchise.

A positive outcome in this trial would provide a further opportunity to both improve patient lives and outcomes as well as drive future growth in our oncology franchise.

Speaker 5: With that, I'll turn it over to Rob for an update on our pipeline and upcoming milestones. Rob? Thank you, Renee. Slide 15 provides an overview of our robust, diversified pipeline that includes neuroscience and oncology programs across all phases of development.

With that I'll turn it over to Rob for an update on our pipeline and upcoming milestones Rob. Thank you Rene Slide 15 provides an overview of a robust diversified pipeline that includes neuroscience and oncology programs across all phases of development.

Consistent with our mission and strategy. These programs are focused on advancing the treatment of serious diseases.

Speaker 5: Consistent with our mission and strategy, these programs are focused on advancing the treatment of serious diseases for which there are limited or no options.

Which there are limited or no options.

Moving to slide 16.

Speaker 5: This is an exciting time for our organization as we approach multiple catalysts across the equally.

This is an exciting time for our organization as we approach multiple catalysts across the pipeline.

We now expect.

Speaker 5: We now expect a five late stage data readouts through 2024.

Five late stage data readouts through 2024.

Speaker 5: with all five addressing areas of significant unmet need.

With all five addressing areas of significant unmet need.

Starting with neuroscience.

Speaker 5: Recruitment in our Phase 3 trial of Epidialics in Japan is progressing well. And we now expect top-line data in the second half of 2024.

<unk> in our phase III trials Epidiorite in Japan is progressing well and we now expect top line data in the second half of 2024.

Speaker 5: We are pleased to announce that we have completed enrollment in our ongoing Phase 2 trial of JCP-150 and PTSD.

We are pleased to announce that we have completed enrollment in our ongoing phase II trial of <unk> in PTSD.

Speaker 5: Based on timing of the last patient last visit.

Based on timing of the last patient last visit.

We are updating the anticipated timing of our topline data readout to January 2024.

Speaker 5: We are updating the anticipated timing of our top line data readout to January 2024.

We also have ongoing trials for <unk>.

Speaker 5: We also have ongoing trials for Suva Caltamide, or JCP-385, and both essential tremor and Parkinson's disease tremor.

<unk> hundred 85 in both essential tremor in Parkinson's disease tremor.

Speaker 5: with top-line data from the ET trial expected in the first half of 2024.

With top line data from the <unk> trial expected in the first half of 2024.

Speaker 5: If results are positive, we believe this trial can serve as part of a pivotal path.

If results are positive we believe this trial could serve as part of a pivotal package.

Speaker 5: In addition, we anticipate initial proof of concept and healthy volunteers later this year for JZP441, our recs and two were after agonist. Moving to on college.

In addition, we anticipate initial proof of concept and healthy volunteers later this year for JP 441.

Orexin two receptor agonist.

Moving to oncology and has added data man.

We expect to report topline data from the ongoing phase III frontline gastroesophageal adenocarcinoma trial next year.

Speaker 5: We expect to report top line data from the ongoing phase three frontline Kestrosophageal adenocarcinoma trial next year.

Later in the call I'll provide an overview of our regulatory strategy presented data mab, including an update on PTC.

Speaker 5: Later in the call, I provide an overview of our regulatory strategy for ZANA DataMab, including an update on BTC. Okay.

Speaker 5: As Renee just mentioned, top line progression free survival data and sub-cellka in combination with dysentric as first line maintenance therapy for extensive stage small cell lung cancer is expected at the end of 2024 or early 2024.

As Rene just mentioned.

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

I will now discuss some of our key programs in detail starting on slide 17 with data management, our highest priority pipeline asset.

Speaker 5: I'll now discuss some of our key programs in detail. Starting on slide 17, it's the end of the data map. Our highest priority pipeline asks.

Speaker 5: Given its potential across multiple HER2 positive tumor types, we are expanding and accelerating our development plans for this exciting knowledge.

Given its potential across multiple her two positive tumor types, we are expanding and accelerating our development plans for this exciting molecule.

Speaker 5: Fenedatimab is a novel bispecific antibody that can simultaneously bind two non-overlapping epitopes of her too, known as bipedal.

<unk> is a novel bi specific antibody that can simultaneously buying two non overlapping epitopes of her too.

Noticed by power toxic findings.

Speaker 5: This unique design results in multiple mechanisms of action, including dual hard-to-signal block aim.

This unique design results in multiple mechanisms of action, including dual her to signal blockade.

Receptor clustering on the cancer cell surface, leading to internalization.

Speaker 5: Receptor clustering on the cancer cell surface, leading to internalization by a viaparotopic binding, and potent immune activation, including antibody dependent cellular cells.

<unk> power topic binding.

And potent immune activation.

<unk> antibody dependent cellular cytotoxicity.

Speaker 5: antibody-dependent cellular phageocytosis and complement dependent cytotoxicity. Leading to encouraging anti-tumor...

Body dependent cellular phagocytosis.

Complement dependent cytotoxicity.

Leading to encouraging anti tumor activity in patients.

Speaker 5: Additionally, Dynadatamab can prevent HER2 from combining with other HER2 proteins and with HERB receptor family members like HER3, which can further block growth sphignol. Dynadatamab has shown compelling activity across a broad range of HER2 expressing puma.

Additionally, standard data math can prevent her two from combining with other her two proteins and with her b receptor family members like her three which can further block <unk> signaling.

Some of the data Mab has shown compelling activity across a broad range of her two expressing tumors.

And we presented promising efficacy and early survival data at <unk> in BTC and ask OTI and Gea earlier this year.

Speaker 5: And we presented promising efficacy and early survival data at ASCO in BTC and ASCO GI and GIA earlier this year.

Speaker 5: Most recently, Beijing, which has development rights in some Asia-Pacific markets outside of Japan, reported results at this year's Asmo meeting from the Phase II trials and a data map in combination with chemotherapy and Tizalizumab Beijing's anti-VD1 antibody. In first line gastric and gastroosophageal junction can't.

Most recently Beijing, which has development rights in some Asia Pacific markets outside of Japan.

Ported results at this year's ESMO meeting from a phase II trial of <unk> in combination with chemotherapy and to Elysium app patients anti PD, one antibody and.

In first line gastric and gastroesophageal junction cancers.

Speaker 5: Data included an overall response rate of 76% with a median duration of response of 22.8 months and a median progression free survival of 16.7 months at the time of the cutoff.

Data included an overall response rate of 76% with a median duration of response of 22 eight months and a median progression free survival of $16 seven months at the time of data cutoff.

Speaker 5: These data, along with our own GEA program, are building a body of evidence supporting the potential of Xana Datamap and treating first-line GEA.

These data along with our own GAA program are building a body of evidence supporting the potential of valid data mab and treating personal lines.

Based on compelling phase II data, we plan to initiate a rolling BLA submission. This year for accelerated approval of <unk> for second line treatment of biliary tract cancer.

Speaker 5: Based on compelling phase two data, we plan to initiate a rolling BLA submission this year for accelerated approval of Zana Data Mad for second line treatment, a billary track cancer. We expect to...

We expect to complete the submission.

Speaker 5: in the first half of 2024, and anticipate that our confirmatory trial and first line BTC will be open and enrolling patients prior to the completion of the Rolling DLA submission.

In the first half of 2024.

We anticipate that our confirmatory trial in first line BTC will be open and enrolling patients prior to the completion of the rolling BLA submission.

Turning to slide 18, BTC and <unk> are the first of multiple indications we plan to pursue for Zander data matters.

Speaker 5: Turning to slide 18, BTC and GEA are the first of multiple indications we plan to pursue from Xamadatimat.

We believe that the data map has the potential to raise the standard of care for some of the most difficult to treat her two expressing cancers, including breast cancer, where we see a significant potential to help patients in both early and late stage disease.

Speaker 5: We believe Zanadena Mab has the potential to raise the standard of care for some of the most difficult to treat her to express in cancer.

Speaker 5: including breast cancer, where we see a significant potential to help patients in both early and late stage disease.

Speaker 5: We're executing a comprehensive development plan and are excited about delivering this innovative therapy to patients. If approved, we expect to initially enter the market in second line BTC, where physicians would gain important experience with Zanadayama.

We are executing a comprehensive development plan and are excited about delivering this innovative therapy to patients. If approved we expect to initially entered the market in second line DTC where <unk>.

Physicians would gain important experience with valid data matters.

Speaker 5: Following BTC, we expect to have a pact to approval and first line GEA with a supplemental BLA submission, which provides a more streamlined approval process compared to a full BLA. We strongly believe that a substantial opportunity remains to address the unmet patient need and first line GEA.

Following BTC, we expect to have a path to approval in first line gea with a supplemental BLA submission, which provides a more streamlined approval process compared to a full BLA. We strongly believe that a substantial opportunity remains to address the unmet patient need.

First slide gea.

Speaker 5: including in the HER2 positive PDL-1 negative patient population.

Including in the her two positive PD lone negative patient population.

Speaker 5: where the standard of care remains trastuzumab plus chemotherapy.

Where the standard of care remains Trastuzumab plus chemotherapy.

Speaker 5: For patients who are PDO-impositive, we believe that SanidataMap has the potential to be the HER2 targeted treatment of choice.

For patients who are PD lone positive we.

We believe this added data map has the potential to be the her two targeted treatment of choice.

Speaker 5: while also combining with a PD1 inhibitor. In order to treat those patients with GIA, this tumor's expressed PDL1.

We're also combining with the PD one inhibitor in order to treat those patients with Ta, whose tumors express PD lone.

There also remains an opportunity to move into earlier stages of <unk>, where we see the potential to help those patients in the neo adjuvant and adjuvant settings.

Speaker 5: There also remains an opportunity to move into earlier stages of GEA, where we see the potential to help those patients in the neo-adjuvant and adjuvant.

Speaker 5: GEA represents a significantly larger patient opportunity compared to BTC and a prior approval in BTC may accelerate adoption into GEA treatment guidelines and programs.

<unk> represents a significantly larger patient opportunity compared to BTC.

In a prior approval in BTC may accelerate adoption into GAA treatment guidelines and protocols.

We look forward to data from the ongoing pivotal phase III <unk> trial expected in 2024.

Speaker 5: We look forward to data from the ongoing pivotal phase 3 G E A trial expected in 2024, which may support US and global regulatory submission.

Each may support U S and global regulatory submissions.

Speaker 5: PressCamps also represents considerable opportunity.

Breast cancer also represents a considerable opportunity.

Speaker 5: reported by promising curly data for Xenodatemab as monotherapy in multiple combinations and across stages of disease and lines of therapy.

Supported by promising early data presented data as monotherapy.

In multiple combinations and across stages of disease and lines of therapy.

Based on the efficacy and safety seen in studies to date, we believe <unk> is well suited for early stage disease, including potential use as neo adjuvant and adjuvant therapy.

Speaker 5: Based on the efficacy and safety seen in studies to date, we believe that the data map is well suited for early stage disease, including potential use as neoage of it and adjuvant error.

Speaker 5: Sani Data Map has also shown promise in HER2 positive and hormone receptor positive breast cancer as part of a novel combination.

Saturday to map has also shown promise in her two positive and hormone receptor positive breast cancer as part of a novel combination.

Speaker 5: based on these encouraging signs of activity. We have ongoing trials in new adjuvant breast cancer, including an arm in the high-spy platform trial.

Based on these encouraging signs of activity, we have ongoing trials and new adjuvant breast cancer, including an arm in the high side platform trial.

Which is studying zama data mab for the neo adjuvant treatment for locally advanced breast cancer.

Speaker 5: which is studying Xana datumab for the new adjuvant treatment for locally advanced breast...

Speaker 5: We are also evaluating the opportunity to expand into both combination regimens and later lines of therapy in HER2 positive and HER2 HR positive breast.

We're also evaluating the opportunity to expand into both combination regimens.

Later lines of therapy in her two positive.

Her to HR positive breast cancer. Finally, we're also evaluating <unk> in multiple early phase trials in other tumor types.

Speaker 5: Finally, we're also evaluating Xana data map and multiple curly phase trials and other tumor types. We're few herty targeted.

Where few her two targeted treatment options are available.

Speaker 5: We are impressed with the strengths of data and clinical activities and a data map has shown across a diverse set of her two expressing indications.

We are impressed with the strength of data and clinical activities out of the data map has shown across a diverse set of her two expressing indications such as colorectal cancer non small cell lung cancer and multiple other cancers, where there continues to be a need for safe and effective targeted treatment options for <unk>.

Speaker 5: such as colorectal cancer, non-small cell lung cancer, and multiple other cancers where there continues to be a need for safe and effective targeted treatment options for...

Patients.

Speaker 5: In summary, we are committed to rapidly advancing and expanding our development program for a molecule that has the potential to transform the current standard of care in multiple her two expressing cases.

In summary, we are committed to rapidly advancing and expanding our development program for a molecule that has the potential to transform the current standard of care in multiple <unk> expressing cancers, turning to slide 19, <unk> Fi, though is our novel highly selective fatty acid amide.

Speaker 5: Turning to slide 19, KZP150 is our novel. Highly select this fatty acid amide hydrolyze or fallen hip.

Julie's or fall inhibitor.

Speaker 5: We are developing JCP-150 as a once daily oral medication with the potential to impact the pathophysiology and symptoms of PTSD.

We are developing <unk> as a once daily oral medication with the potential to impact the pathophysiology and symptoms of PTSD.

By addressing the underlying cause of PTSD.

Speaker 5: By addressing the underlying cause of PTSD, impairment of fear extinction and its consolidation, JCP-150 has the potential to improve patients' associated symptoms, such as anxiety, insomnia, and nightmares. Preclinical and early clinical data showed activity on fear extinction and stress.

Chairman of fear extinction and its consolidation.

<unk> has the potential to improve patients associated symptoms such as anxiety.

Sameer and nightmares preclinical and early clinical data showed activity on fear extinction stress response.

Speaker 5: JCP-150 has a novel and promising mechanism of action, providing irreversible inhibition of thought, which we believe they have advantages over reversible thought inhibitors in development, and we anticipate top line data readout in January , 2020.

<unk> has a novel and promising mechanism of action, providing irreversible inhibition of <unk>, which we believe may have advantages were reversible <unk> inhibitors in development and we anticipate topline data readout in January 2024.

Speaker 5: On slide 20, I'll highlight JCP-441, a potent, highly selective, erection-2 receptor agonist designed to activate and restore impaired erections phenol.

On slide 20 highlights ACP 441, a potent highly selective orexin two receptor agonist designed to activate and restore impaired <unk> signal.

Speaker 5: Through this mechanism of action, JCP 441 has the potential to exert pronounced weight promoting effects in people with sleep disorder.

Through this mechanism of action <unk> 441.

The potential to exert pronounced wake promoting effects in people with sleep disorders.

Speaker 5: Erections are excitatory neuropeptides.

Our actions are excited Terry neuropeptides.

Speaker 5: I played an important role in the regulation of sleep and wake

Play an important role in the regulation of sleep and wakefulness.

Speaker 5: Patients with type 1 narcolepsy have a loss of erection producing neurons with impaired erection signaling. And clinically, these patients often present with chronic disabling symptoms that significantly impact patient's ability to function normally during the day.

Patients with type one narcolepsy have a loss of orexin, producing neurons with impaired Rx and signaling and clinically these patients often present with chronic disabling symptoms.

Significantly impact patients' ability to function normally during the day.

Speaker 5: Slide 21 illustrates the design of our Phase 1 program, evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics at JCP 441 and help you volunteers.

Slide 21 illustrates the design of our phase one program evaluating safety Tolerability pharmacokinetics and pharmacodynamics.

<unk> 441 in healthy volunteers.

Our single ascending dose study is being conducted in sleep deprived healthy volunteers and includes an evaluation of the weight promoting effects of JCB 441, using the maintenance of wakefulness test or <unk>.

Speaker 5: Our single-offending dose study is being conducted in sleep deprived healthy volunteers and includes an evaluation of the weight promoting effects of JCP-441 using the maintenance of weightfulness tests for MWP.

Speaker 5: This is a recognized disease model that historically has translated to patient F.

This is a recognized disease model that historically has translated to patient efficacy.

Speaker 5: We also have an ongoing study evaluating multiple sending daytime doses and healthy volunteers intended to provide safety of chronic dosing in support of a multiple dose study in patients.

We also have an ongoing study evaluating multiple ascending daytime doses in healthy volunteers intended to provide safety of chronic dosing and supportive of multiple dose study in patients.

Speaker 5: Importantly, we have structured the program to maximize our learnings at this stage, including identifying appropriate dose ranges, which we believe will accelerate later development and pace. We have created a new program to maximize our learnings at this stage, including identifying appropriate dose ranges, which we believe will accelerate later development and pace.

Importantly, we have structured the program to maximize our learnings at this stage, including identifying appropriate dose ranges, which we believe will accelerate later development in patients.

Speaker 5: We're excited about the potential of JCP 441 and look forward to updating you on our progress later this year.

We're excited about the potential of JCB for one and look forward to updating you on our progress later this year.

Turning to slide 22, our team is advancing multiple preclinical compounds toward clinical stage development.

Speaker 5: Turning to slide 22. Our team is advancing multiple preclinical compounds toward clinical stage development.

J J P. A one five a molecule that has emerged from our collaboration with redox.

Speaker 5: JCP 815, a molecule that has emerged from our collaboration with red X.

Speaker 5: is one of our most recently initiated phase one trial.

As one of our most recently initiated phase one trials.

<unk> hundred five is a highly selective potent pan RAF inhibitor with a differentiated mechanism of action.

Speaker 5: JCP 815 is a highly selective potent pan-raff inhibitor, with a differentiated mechanism of F.

Speaker 5: It targets specific components of the mitogen-activated protein kinase pathway that are known on caegenic drivers. Active against multiple A-Raff, B-Raff, and C-Raff mutants, and a spectrum of B-Raff users.

To target specific components of the mitogen activated protein kinase pathway that are known oncogenic drivers active against multiple a RAF and BRAF and <unk> mutants and a spectrum of BRAF fusions.

Speaker 5: Activity against ARAF mutants may be an important point of differentiation. As recent data suggests the importance of ARAF in the context of mutant RAS activation.

Activity against a Ras mutants may be an important point of differentiation as recent data suggests the importance of hey, RASK in the context of mutant Ras activation.

Speaker 5: JCP 815 also, hopefully inhibits both monomer and dimer-driven graph signaling and prevents paradoxical pathway activation induced by p-raft selective inhibition.

<unk> hundred five also potently inhibits both monomer dimer, driven Ras signaling and prevents paradoxical pathway activation induced by <unk> selective inhibition.

Slide 23 illustrates the design of the ongoing <unk> hundred five phase one trial evaluating safety dosing pharmacokinetics pharmacodynamics and initial anti tumor activity of <unk> five.

Speaker 5: Slide 23 illustrates the design of the ongoing JCP 815 phase 1 trial, evaluating the safety, dosing, pharmacokinetics, pharmacodynamics, and initial anti-tumor activity of JCP 815 in participants with advanced or metastatic solid tumors harboring mutations in the MAP kinase pathway. I pay a vial for each one of theipATH cells associated with the wells.

Participants with advanced or metastatic solid tumors harboring mutations in the map kinase pathway.

It consists of two parts.

Speaker 5: Part A will characterize the safety and tolerability of JCP-815, determining a maximum tolerated dose and PK profile, and determine a recommended phase two dose to be further investigated in the expansion phase or Part B.

Part a will characterize the safety and Tolerability of <unk> hundred five determining a maximum tolerated dose and PK profile.

And determine our recommended phase II dose to be further investigated in the expansion phase or part b.

Speaker 5: Part B will investigate the anti-tumor activity at the recommended phase 2 dose in various tumor types based on mutation status.

Part B will investigate the anti tumor activity at the recommended phase II dose.

In various tumor types based on mutation status.

Speaker 5: Overall, our R&D team has been advancing multiple programs from our neuroscience and oncology pipeline, and we have multiple upcoming catalysts and near-term data reading.

Overall, our R&D team has been advancing multiple programs from our neuroscience and oncology pipeline and we have multiple upcoming catalysts and near term data readouts.

Speaker 3: Now I will turn the call over to Bruce for a financial update. Bruce, thanks Rob. I'll start with our top and bottom line results on slide 25. As a reminder, our full financial results are available in our press release and 10Q.

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

Thanks, Rob I'll start with our top and bottom line results on Slide 25, as a reminder, our full financial results are available in our press release and 10-Q.

Speaker 3: In the third quarter of 2023, we achieved 972 million in total revenue.

In the third quarter of 2023, we achieved 972 million in total revenues driven by continued growth of our key products in both neuroscience and oncology. We're pleased with the continued trajectory of highways during a period when high sodium oxalate competition has been introduced into the market.

Speaker 3: driven by continued growth of our key products in both neuroscience and oncology. We're pleased with the continued trajectory of ZiWave during a period when high sodium oxabate competition has been introduced into the market.

Speaker 3: Coupled with Epidiolex momentum, the strong growth of Rylase, and solid performance of Zeptelka, total revenue increased 3% compared to the third quarter of 2022.

Coupled with Hopper dielectric momentum the strong growth of Reillys and solid performance of <unk> total revenue increased 3% compared to the third quarter of 2022.

Our adjusted net income for the quarter was $340 million and we reported adjusted EPS of $4 84.

The decreases in Eni and EPS this quarter compared to the same period last year were driven primarily by an increase in R&D investments, partially offset by higher revenues and lower effective tax rate.

Speaker 3: The decreases in ANI and EPS this quarter compared to the same period last year were driven primarily by an increase in R&D investment, partially offset by higher revenues and lower effective tax rates.

Speaker 3: The majority of our R&D increase this quarter is related to Xanny data.

The majority of our R&D increase this quarter is related to sandy data map.

Our adjusted EPS also reflects a lower number of diluted shares outstanding compared to the same period last year.

Speaker 3: Our adjusted EPS also reflects a lower number of diluted shares outstanding compared to the same period last year.

Speaker 3: We continue to generate significant cash from our business. We recorded 307 million of cash from operations in the quarter and 925 million through the first three quarters of the year.

We continued to generate significant cash from our business, we recorded $307 million of cash from operations in the quarter and $925 million through the first three quarters of the year.

Speaker 3: Our strong overall financial position means we have significant flexibility to invest in priority commercial and R&D programs as well as corporate development opportunities.

Our strong overall financial position means we have significant flexibility to invest in priority commercial and R&D programs as well as corporate development opportunities.

Turning to slide 26, we have raised the midpoint of our full year 2023 revenue guidance to a range of $3 75 billion to $3 875 billion.

Speaker 3: Turning to slide 26, we have raised the midpoint of our full year 2023 revenue guidance to a range of 3.75 billion to 3.875 billion.

Speaker 3: As a reminder, we raised revenue guidance last quarter, and have continued our strong commercial execution on key growth drivers, Zaywev, Epidilects, and Riley.

As a reminder, we raised revenue guidance last quarter and have continued our strong commercial execution on key growth drivers Lightwave dialects and reilly's our guidance represents year over year total revenue growth, even as we face the headwind of oxalate competition.

Speaker 3: Our guidance represents your over your total revenue growth even as we face the headwind of oxalate competition.

Speaker 3: Our 2023 neuroscience guidance remains unchanged and reflects expectations of continued growth of Zywave and Epidilex, offset by the expected decline in Zyrem with a revenue range of 2.715 2.825 billion.

Our 2023 neuroscience guidance remains unchanged and reflects expectations of continued growth of XI wave and up a dialects offset by the expected decline in xyrem with a revenue range of $2 $71 5 billion to $2 82 5 billion.

With regard to high sodium authorized generics royalties from high sodium oxalate Ags were $29 million in third quarter of 'twenty, three which reflect a significant increase over the first half as we move to a six month fixed rate royalty per the AG agreement with Hikma.

Speaker 3: With regard to high sodium authorized generics, royalties from high sodium oxabate AGs were $29 million in third quarter of 23, which reflect a significant increase over the first half as we move to a six month fixed rate royalty per the AG agreement with HIC.

Speaker 3: The royalty rate will increase again after this six month period, at which point it will remain fixed for the duration of this agreement.

The royalty rate will increase again after the six month period at which point it will remain fixed for the duration of this agreement.

AG royalties are included in our neuroscience guidance, we have raised the midpoint of our 2023 oncology revenue guidance to a range of 975 billion to 1.05 billion, which reflects 16% growth at the midpoint.

Speaker 3: AG wrote, he's are included in our Neuroscience Guide.

Speaker 3: We have raised the midpoint of our 2023 oncology revenue guidance to a range of 975 million to 1.05 billion, which reflects 16% growth at the mid-

I'd like to draw your attention to several items on slide 27.

Speaker 6: I'd like to draw your attention to several items on Flight 27.

Speaker 6: Our strong cash generation combined with our discipline capital allocation provides us with flexibility to make strategic investments in our business.

Our strong cash generation combined with our disciplined capital allocation provides us with flexibility to make strategic investments in our business. This includes an increase to our R&D guidance and an increase to the midpoint of our SG&A guidance, while remaining on track to deliver anti growth in 2023.

Speaker 6: This includes an increase to our R&D guidance and an increase to the midpoint of our S-DNA guidance while remaining on track to deliver an I-growth in 2023 compared to 2022. Our updated guidance midpoints equate to an adjusted operating margin of approximately 44%.

Compared to 2022 or.

Our updated guidance mid points equate to an adjusted operating margin of approximately 44%.

Speaker 6: While margins will vary over time, we believe we are well positioned to achieve our Vision 2025 goal of driving a 5% improvement from 2021 to 2025.

While margins will vary over time, we believe we are well positioned to achieve our vision 2025 goal of driving a 5% improvement from 2021 to 2025.

One note regarding Eni as we look to the future.

Speaker 6: One note regarding ANIs we look to the future. In the third quarter, we benefited from a lower effective tax rate, primarily driven by tax benefits derived from our increased R&D expenditure, expiration of statutes of limitation, and changes in product mix.

In the third quarter, we benefited from a lower effective tax rate, primarily driven by tax benefits derived from our increased R&D expenditure expiration of statutes of limitation and changes in product mix, we expect that our ETR will increase next year as global tax rates are harmonized.

Speaker 6: We expect that our ETR will increase next year as global tax rates are far more than

Speaker 6: Consistent with our capital allocation strategy, our enhanced investment in R&D is a direct result of our success in diversifying and advancing our pipeline.

Consistent with our capital allocation strategy, our enhanced investment in R&D is a direct result of our success in diversifying at advancing our pipeline.

Speaker 6: We've increased our R&D guidance for 2023 to a range of 780 million to 820 million, reflecting our confidence in our pipeline programs. In particular, we are making substantial investments in Zany Data Map to more aggressively pursue development opportunities that we believe will benefit patients and create long-term value for jobs.

We've increased our R&D guidance for 2023 to a range of $780 million to $820 million, reflecting our confidence in our pipeline programs. In particular, we are making substantial investments in any data map to more aggressively pursue development opportunities that we believe will benefit patients and create long term value.

For jobs.

Looking at SG&A, we are updating our guidance to a range of 1.065 billion to $1 105 billion as we invest in a disciplined manner to drive further growth in key brands.

Speaker 6: Looking at SGNA, we are updating our guidance to range of 1.065 billion to 1.105 billion, as we invest in the discipline managed drive further growth in key brands.

Speaker 6: We believe there is tremendous unrecognized value potential in our stock. We therefore continued share repurchases under our existing repurchase program. In the third quarter, we completed approximately $75 million of share repurchase.

We believe there is tremendous unrecognized value potential in our stock. We therefore continued share repurchases under our existing repurchase program in the third quarter, we completed approximately $75 million of share repurchases.

Speaker 6: At the end of the third quarter, approximately $261 million remained available for share repurchases under our current-

At the end of the third quarter approximately $261 million remained available for share repurchases under our current plan importantly.

Importantly, given our strong overall financial position, we are able to include share repurchases and our capital allocation strategy without compromising our ability to execute business development opportunities and invest in our innovative R&D programs.

Speaker 6: Additionally, we are reiterating our adjusted EPS guidance of $18.15 to $19.00. I'll conclude our

Additionally, we are reiterating our adjusted EPS guidance of $18 15 to $19.

I'll conclude our prepared remarks on slide 29.

Speaker 6: Our top-line performance this quarter was driven by focused execution and strong commercial results, evidenced by the durability of our Oxybate franchise, continued growth of epidiolex, and strength of our oncology business.

Our topline performance this quarter was driven by focused execution and strong commercial results evidenced by the durability of our oxalate franchise continued growth of epic dialogues and strength of our oncology business.

We continue to advance our pipeline invest in long term growth and we expect up to five late stage data readouts through 2024 that have the potential to further diversify and transform our business.

We remain focused on strategic capital allocation.

Speaker 6: with our strategic investments, 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.

With our strategic investments 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 6: That concludes our prepared remarks. I'd now like to turn the call over to the operator to open the line for Q&A.

That concludes our prepared remarks, I'd now like to turn the call over to the operator to open the line for Q&A.

Speaker 1: As a reminder, if you would like to ask a question, please press star one on your telephone keypad. We ask that you limit yourself to one question.

As a reminder, if you would like to ask a question. Please press star one on your telephone keypad, we ask that you limit yourself to one question.

Speaker 1: Your first question comes from the line of Jessica Fye from J.P. Morgan. Please go ahead.

Your first question comes from the line of Jessica Fye from J P. Morgan. Please go ahead.

Hey, guys. Good afternoon. Thanks, so much for taking my question.

Speaker 7: Hey guys, good afternoon. Thanks so much for taking my question. This might be a little tricky to respond to, but recently there were some headlines stating that Jazz might be exploring various strategic options, including breaking up the company or sale of a business unit. I generally think of Jazz as more likely to buy a business than to sell a business, but is there anything you want to clarify for folks with respect to how you're thinking about business development and the strategy? Thanks.

Just maybe a little tricky to respond to but recently there were some headlines stating that jazz might be exploring various strategic options, including breaking up the company or sale of a business unit.

Generally think of jazz is more likely to buy a business. Some solid business, but is there anything you want to clarify for folks with respect to how you're thinking about business development and the strategy.

Jess welcome back could you hear your voice.

Speaker 6: Jess, welcome back. Good to hear your voice. So I'll point out that Jazz made no such announcement. There were, you know, a story in one place with unnamed sources.

So I'll I'll point out the jazz made no such announcement there were.

Our story and in one place with unnamed sources.

Speaker 6: I'll also remind you as an Irish takeover panel company that you know we can be forced to clarify publicly if there's something actually going on in pretty short order and that did not happen.

I'll also remind you as an Irish takeover panel company that.

We can be forced to to clarify publicly if there's.

Something actually going on in pretty short order and that did not happen.

Speaker 6: We remain very focused on corporate development as a way to grow our business. That's been part of our strategy historically.

We remain very focused on corporate development as a way to grow our business, but that's been part of our strategy. Historically, it's specifically called out as part of vision 2025, and we think the strong financial position of the company ending the quarter with $1 6 billion in cash our strong cash flow of 925.

Speaker 6: We have typically called out as part of Vision 2025, and we think the strong financial position of the company ending the quarter with 1.6 billion in cash, the strong cash flow of $925 million over the first three quarters. The substantial continued de-leveraging of the company put us in really good position to continue to put cash to work, to grow our...

Over the first three quarters. The substantial continued deleveraging of the company put us in really good position to continue to put cash to work to grow our business.

Your next question comes from the line of Jason <unk> from Bank of America. Please go ahead.

Speaker 1: Your next question comes from the line of Jason Gerberi from Bank of America. Please go ahead.

Okay.

Oh, Hey, guys.

Speaker 8: So, hey, guys, thank you for taking my question. I guess mine will be around the evolving competitive landscape in the space with the rise and.

Thank you for taking my question I guess mine will be around the evolving competitive landscape and in the oxalate space with loom ryzen.

Speaker 8: You know, they had an update this morning about a lot of thousand patient enrollment forms. Just curious, you know, your guidance suggests that nothing's really changed relative to your assumptions regarding competition from the start of the year until now. But just curious, you know, if you would...

They had an update this morning about about 1000 patient enrollment forms just curious.

Your guidance suggests that nothing's really changed relative to your assumptions regarding competition from the start of the year till now, but just curious if you would.

Speaker 8: You know, if you're seeing anything in the marketplace, worth noting, or if you think that ultimately, maybe the competitor is just getting more of its business from either naive or our patients who have discontinued Zaiwave historically, that would be helpful.

If youre seeing anything in the marketplace worth worth, noting or if you think that.

<unk>, maybe the competitor is just getting more of its business from either naive or patients who have discontinued them.

Historically that would be helpful. Thanks.

Yeah, Jason Thanks for the question and before I turn it over to Kim for a little more color I'll just say in your comments Youre exactly right that we foresaw.

Speaker 6: Yeah, Jason, thanks for the question. And before I turn it over to Kim for a little more color, I'll just say, in your comments, you're exactly right, that we foresaw competition in the Oxybate space this year, both from authorized generics of Xyrem and the branded fixed-dose high-sodium product and built that into our guidance. We've actually raised our neuroscience guidance last quarter and continue to perform in line with our guidance.

Competition in the oxalate space this year, both from authorized generics of Xyrem and the branded <unk>.

Fixed dose high sodium product and built that into our guidance, we've actually raised our neuroscience guidance.

Last quarter.

And continue to perform in line with our guidance.

Speaker 6: But, Kim, maybe you could give a little more color on the oxabay landscape.

But Tim maybe you could give a little more color on the oxalate landscape.

Speaker 9: Yeah, sure. So, yes, it is still growing in Narcolepsy. We're pleased to see, you know, despite the additional competition from the high sodium oxybates were introduced this year. You know, our growth in Narcolepsy has slowed in line with our expectations, you know, in our own forecast.

Yes, sure. So yes, <unk> is still growing in Knoxville narcolepsy, we're pleased.

Despite the additional competition from the high 30, Max Batzer introduced this year our net.

Net growth in narcolepsy has slowed in line with our expectations and our own forecast as they remove fewer available patients to transition from Xyrem given our early success with <unk> and some patients have decided to go ahead and give <unk> a try and generally in terms of what we're hearing.

Speaker 9: As they remain fewer available patients to transition from thyrum, given our early success with thy weight.

Speaker 9: and some patients have decided to go ahead and give FK2 and A a try. Generally in terms of what we're hearing from healthcare providers right now is that they're still telling us that they play safe.

From health care providers right now is that they are still telling us that they playful high value on both the low sodium value proposition evaluate as well as the fact, they've gotten used to boom over the individualized or customize the dosing regimen for individual patients depending on their needs.

Speaker 9: I value on both the low sodium value proposition of thyweight as well as on the fact they've gotten used to being able to individualize or customize the dosing regimen for individual patients depending on their needs.

Speaker 9: Many ACPs have expressed an interest in gaining eventually some experience with the new fixed dose high sodium oxidative product and where they're typically doing that they're telling us, you know, is among those patients that have come in and really insisted on giving it a try. So overall, you know, we remain, you know, very confident in the strength and durability of our Oxidate franchise. We do say see as I always continuing to be the oxidative choice.

Many acp's have expressed an interest on gaming eventually some experience with the new fixed dose high sodium activate product and where they're typically doing that they are telling us.

Among those patients that have come in and really insisted and giving it a try.

So overall, we remain very confident in the strength and durability of our activate franchise.

We do so.

We are continuing to be the activated choice now and in the future and it is still the only one approved two for the treatment of idiopathic hypersomnia and lastly, when we continue to look at our data in terms of those portion of patients who are naive to activate treatment. They are being started on their first.

Speaker 9: now and in the future and it is still the only one approved to for treatment of idiopathic hypersomnia. And lastly, when we continue to look at our data in terms of...

Speaker 9: Those portion of patients who are naive to oxybate treatment, they're being started on their first oxybate treatment. The vast majority of these patients continue to be being initiated on thy wave. So we think that's very strong evidence that overall overwhelmingly physicians still feel it's most important to focus on the patient's long-term.

Activate trade routes the vast majority of these patients continue to be being initiated on <unk>.

<unk>. So we think that's been a very strong evidence that overall overwhelmingly physicians still.

Important to focus on the patient long term health.

Speaker 1: Your next question comes from the line of Ami Fadia from Needham and Company. Please go ahead.

Our next question comes from the line of Amit Bhatia from Needham and company. Please go ahead.

Hi, Good evening. Thanks for taking my question mine is on GBP 150.

Speaker 10: Hi, good evening. Thanks for taking my question. Mine is on JCP 150. Can you talk about sort of mechanistically why you think that.

Can you talk about sort of Mechanistically why you think that.

It could be one five seasons mechanism.

Speaker 10: SCP-150 mechanism is perhaps a differentiated, then irreversible fine inhibition. And with regards to your ongoing trial, with regards to the gaps five end points.

Perhaps a different shaded.

And her first about <unk> inhibition and with regards to your ongoing trial it took off to the caps five endpoint.

Speaker 10: What would you say, what would you consider as a clinically meaningful change that you would like to see? And the regards to your trial, can you talk about powering, should we expect to see a strictly meaningful result? And if you could go back and explain why the Lord knows, why you have two doses in the trial and not just the higher dose. Thank you.

What would you say.

What would you consider as a clinically meaningful change that he would like to see and with regards to your trial can you talk about having you know should we expect to see a particularly meaningful.

And if you could go back and explain why the low dose what why you have two doses in the trial and not just the higher dose. Thank you.

Rob.

Yeah. Thanks, Bruce Thank you for the question on me.

Speaker 5: So, starting with the first part of that around why the mechanism is differentiated, I would first say that we think we're interested in JCPOA 150 because of PHA as an underlying part of the.

So starting with the first part of that around why the mechanism is differentiated I would first say that we think we are interested in <unk> because of fire and underlying part of the.

Speaker 5: pathophysiology potentially. So we know that PTSD patients have...

Physiology, potentially so we know that PTSD patients have.

Speaker 11: low levels of an endomide by inhibiting fog and raise those levels. So we think this is one of the mechanisms that potentially directly addresses the underlying path of physiology.

Low levels of Fernando by inhibiting file you can raise those levels. So we think this is one of the mechanisms that potentially directly addresses the underlying pathophysiology.

Speaker 11: We think we're differentiated in being irreversible, as you mentioned, because you can create a more sustained fall inhibition. In other words, you ultimately have to recenten the size.

I think were differentiated and being irreversible as you mentioned because you can create a more sustained inhibition.

<unk> inhibition in other words.

Ultimately have to re synthesize.

Speaker 11: in order to get back to baseline level. It just allows for consistent inhibition of thought, which we think is more important. In terms of clinically meaningful effect sizes, we haven't said what we're necessarily striving for in this, but you could certainly look...

In order to.

In order to get back to baseline levels and it just allows for consistent inhibition of <unk>, which we think is.

Which we think is more important.

In terms of clinically meaningful effect sizes, we havent said what were necessarily striving for in this but you could certainly look.

Speaker 11: across different mechanisms and see what has been achieved in terms of the CAHPS 5.

Across different mechanisms and see what what has been achieved in terms of the caps five.

Speaker 11: In our trial, we think we're certainly well powered, you know, for clinically meaningful effect.

Our trial, we think we're certainly well powered.

For for a clinically meaningful effect.

Speaker 11: given the 270 patients that we've enrolled across those.

Given the 270 patients that we've enrolled across those.

Speaker 11: And to your point about a low dose and a high dose, in this trial we included two dose levels because we wanted to evaluate what we felt was

Three arms.

And to your point about a low dose and a high dose in this trial. We included two dose levels because we wanted to evaluate what we felt was based on prior.

Speaker 11: Based on prior receptor occupancy data, full constant inhibition versus a lower dose that would be just under that full inhibition and that sort of bracket.

Receptor occupancy data.

Constant inhibition.

Versus a lower dose that would be.

Just under that full inhibition in that set of brackets.

Speaker 11: The range of exposures that you might want to see allows us to collect safety data in that range and then would put it in a better position to select those for a pivotal trial. You know, if and when we move forward.

Range of exposures that you might want to see allows us to collect safety data in that range and then would put us in a better position to select doses for a pivotal trial.

If and when we move forward with that.

Speaker 1: Your next question comes from the line of Mark Goodman from LearRink Partners. Please go ahead.

Your next question comes from the line of Marc Goodman from Leerink Partners. Please go ahead.

Speaker 12: Yeah, with something you could give us a little flavor on what's going on with the subzelket seems to finally have grown after many quarters just seeming flat so you can just give us a little color there. And then could you just give us the total oxybate patient number fours please? Thanks.

Yes, I was hoping you could give us a little flavor on what's going on with the <unk> seems to finally have grown after many quarters just seeming flat. So if you could just give us a little color. There and then could you just give us the total oxalate patient number Forrest. Please thanks.

Yeah I'll take the second part of the question first and then Kevin maybe you could jump in on <unk> growth, which I agree look really nice this quarter.

Speaker 6: Yeah, I'll take the second part of the question first, and then maybe you could jump in on Zepzelka growth, which I agree looked really nice this quarter. On total oxidative patients, we've stopped giving that number.

On total oxyntic patients, we've stopped giving that number.

Speaker 6: As you noticed in the royalty revenue off the AG of $29 million during the quarter, that has jumped up significantly. And that revenue, of course, is derived from patients that would not be included.

As you noticed in the royalty.

Revenue off the AG of $29 million during the quarter that has jumped up significantly and that revenue of course is derived from patients that would not be included.

Speaker 6: across Zywave and Zyrem, so essentially total patients doesn't track to our revenues anymore because that Zyrem plus Zyrem royalty is a little bit distinct.

Across XI wave and Ziram, so essentially total patients doesn't track to our revenues anymore, because that xyrem plus xyrem royalty.

<unk> is a little bit distinct.

Speaker 3: We've continued to give patient numbers in narcolepsy and idiopathic hypersomnia as we exit a quarter to give you a sense of growth.

Continued to give patient numbers in narcolepsy entity Pathic hypersomnia as we exited the quarter to give you a sense of growth.

Speaker 3: of the Zywave asset, but I'll just point out total revenues and total patients don't track the way they have historically for Jazz until this quarter. In the first half of the year at the much lower

The XI wave asset, but I will just point out total revenues and total patients don't track the way they have historically for jazz until this quarter and the first half of the year at the much lower.

Speaker 6: royalty rate on the AG and earlier at the AG launch, the difference wasn't significant. It is significant now and will only continue to be.

Royalty rate on the AG and earlier at the AG launched two difference wasn't significant it is significant now and will only continue to be.

Speaker 6: On ZepZelka, you know, I'll just point out, we're really happy with this deal. When I talk about why we do corporate development and add new growth assets to the company, I think ZepZelka, having generated over $800 million in revenue since launch, you know, has shown that to be a deal that was highly accretive and continues to reward our investors. So, Kim, you want to talk about dynamics there?

On Sept Zilkha.

I'll just point out.

Happy with this deal when I talk about why we do corporate development and add new growth assets to the company and I think so.

<unk> silica, having generated over $800 million in revenue since launch.

Shown that to be a deal that was highly accretive.

And continues to reward our investors so Jim you want to talk about dynamics there.

Speaker 9: Yeah, really happy with the 11% year-over-year growth we saw in the third quarter. And we'll say that the increased demand this quarter is partially attributed to the temporary platinum chemotherapy shortage that unfortunately the U.S. is going through, which did lead VELTA to be used in some patients who oncologists may have historically re-challenged with another round of platinum therapy after their first-line platinum treatment. And we've really been emphasizing for some time that this is where the results with VELTA are most impressive, but it's been difficult getting some of the customers to make this switch.

Yeah, really happy with the 11% year over year growth, we saw in the third quarter and we will say that the increased demand. This quarter is partially attributed to the temporary platinum chemotherapy shortage that unfortunately.

As Boeing through which did lead.

You know that delta can be used in some patients who oncologist may have historically re challenged with another round of platinum therapy. After their first line platinum treatment and we've really been emphasizing for some time, but this is where the results are most impressive.

But it's been difficult in getting some of the customers to make the switch.

Speaker 9: We did roll out this past few months, some new data that we hadn't shared with customers before in this platinum-sensitive patient population to help them feel more comfortable using it. We shared the secondary endpoint results we had around overall survival and progression-free survival. So I think the combination of that data with the shortage of chemotherapy did lead many customers to give it a try there. And largely we think that they're seeing positive results that even when the platinum supply shortage...

We did roll out this.

Past few months.

New data that we hadn't shared with customers before in the platinum sensitive patient population.

Help them feel more comfortable using that we shared.

Kundera endpoint results, we had around overall survival and progression free survival. So I think the combination of that data with the shortage of chemotherapy did lead many customers to give it a try there.

We think that they're seeing positive results that even when the platinum supply shortage.

<unk> continues to improve which we hope it does we do anticipate that some of these health care providers.

Well some of them may revert back to their previous practice of re challenged with platinum others may not reach for that Delta.

More often.

In addition, we saw many HCP is getting experience with this product in the community an outpatient setting.

And we're really impressed with the ease of administration as well as the clinical profile. The numbers itself that doesn't require any inpatient monitoring. So again that business that we think may continue to be a bit sticky after the shortage. So overall it is itself is well established as a treatment of choice in second line.

Speaker 13: monitoring. So again, that business that we think may continue to be a bit sticky after the shortage. So overall, you know, the Delta is well established as the treatment of choice and second line, small cell lung cancer. And we think we've gotten some nice momentum here from this market event. But we really do see most of the opportunity for future growth in this brand coming from the first line setting. And we've got a phase three trial going on there now. Your next question comes in the line of biology preside from Barclays Capital. Please go ahead. I thank you for the questions.

Speaker 9: So, overall, you know, ZipDelta is well-established as the treatment of choice in second-line small cell lung cancer, and we think we've gotten some nice momentum here from this market event. But we really do see most of the opportunity for future growth in this brand coming from the first-line setting, and we've got, you know, a phase three trial going on there now.

Small cell lung cancer, and we think we've gotten some nice momentum here from this market events, but we really do see most of the opportunity for future growth in this brand coming from the first line setting and we've got a phase III trial going on there now.

Your next question comes from the line of Biologic <unk> Prasad from Barclays Capital. Please go ahead.

Speaker 1: Your next question comes from the line of Balaji Prasad from Barclays Capital. Please go ahead.

Speaker 13: Hi, thank you for the questions. Looking at what's not covered on Epidailex, could we, unlike the well-defined patient populations in NACLAFC or IH or oncology, this is one where the market sizing still seems incomplete?

Hi, Thank you for taking the questions.

Looking at more some color on it put our legs could we.

Unlike the well defined patient populations and narcolepsy are I urge our oncology. This is one where the market sizing still seems incomplete. So can you discuss the opportunity in the adult settings. As you spoke about this afternoon.

Speaker 13: So can you discuss the opportunity in the adult settings as you spoke about this afternoon and the additional XUS launches and what would this translate to in terms of an expansion of market size?

On the additional ex U S launches and what would this translate to in terms of an expansion of <unk>.

Market size.

Speaker 13: Maybe an extended related question as you continue to call out that it's well-known sway to a billion dollars. What can we expect beyond this in terms of long-term growth or the trajectory is that we are going to meet single digits or high single digits. How can we think about it? Thank you.

Maybe an extended unrelated question.

Continued to call out so well on its way to $1 billion. What can we expect beyond this in terms of longer term growth trajectory isn't going to be mid single digits or high single digits. How can I think about it. Thank you.

Hey, Thanks for the question <unk> I'll jump in on that one so I'll just note.

Speaker 4: Thanks for the question, Bellagio. I'll jump in on that one. So I'll just note as

Speaker 4: You know, we don't provide product-specific guidance, but I will comment on the broader opportunity, and then I'll turn it to Kim to talk about some of the very specific

You know, we don't provide product specific guidance, but I will comment on the broader opportunity and then I'll turn it to Ken to talk about some of the very specific dynamics that we're seeing in the U S. So when you think about the growth that we saw in the current quarter, we had 9% year over year.

Speaker 4: dynamics that we're seeing in the US. So when you think about the growth that we saw in the current quarter, we had 9% year over year, but importantly we had 14% if you look at the first nine months of this year compared to the prior period. So we are confident we're on track for blockbuster status and in line with our vision 2025 expectation.

But importantly, we had 14% if you look at the first nine months of this year compared to the prior period. So we are confident we're on track for blockbuster status and are in line with our vision 2025 expectations.

Speaker 4: And I think, you know, when you think about Epidiolex, there are three areas to keep in mind in terms of important growth drivers. One, this is a global product, as you've noted. That means global opportunities for expansion and growth were now approved and reimbursed in 24 different countries. We have the pivotal study underway in Japan, which we expect to read out at the end of next year. And then we have strong underlying demand growth also in the U.S., which Kim will comment on in a moment.

And I think.

When you think about the dialects there are three areas to keep in mind in terms of important growth drivers. One. This is a global product as you've noted that means global opportunities for expansion and growth. We're now approved and reimbursed in 24 different countries. We have the pivotal study underway in Japan, which.

We expect to read out at the end of next year and then we have strong underlying demand growth also in the U S, which Kevin will comment on in a moment.

Speaker 4: We also view Epidiolex, continue to view this as very much a long-lived durable asset. We have a robust portfolio of Orange Book listed patents, the majority of which go out to 2035, but also 2039.

We also view at the dialects continue to view this as very much a long lived durable asset we have a robust portfolio of Orange book listed patents the majority of which go out to 2035, but also 2039.

Speaker 4: We do see this as something that is very much a long-term revenue driver for the company. And then third, perhaps most importantly, it's a highly differentiated treatment. Epidialyx is very well characterized and tolerated, which of course lends itself well to polypharmacy, which is the norm in this area. We've generated significant data around its use, which HCPs are have returned to vaccinate shots.

Do you see this as something that is very much a long term revenue driver for the company.

And third perhaps most importantly, it's a highly differentiated treatment at the dialect is very well characterized and tolerated which of course aligns itself, while the polypharmacy, which is the norm in this area. We have generated significant data around it's used with hcp's are finding helpful.

Speaker 4: And this really underpins our investment in data, such as the Epicom study that I mentioned before. And all three of these main factors give us collective confidence in that long-term potential. Specific to some of the XUS dynamics, we had a number of launches in different countries and across different indications, across 23. And we expect that to continue in 2024.

And Thats really underpins our investment in data such as the <unk> study that I mentioned before and all three of these main factors give us collective confidence in that long term potential specific to some of the.

Ex U S dynamics, we had a number of launches in different countries and across different indications across 23, and we expect that to continue in 2024.

Speaker 4: So maybe I'll turn it to Kim to comment on adult long-term care segments and other demanders, sorry, drivers of demand.

So maybe I'll turn it to Ken to comment on adult for long term care segments, and other demand or sorry drivers of demand.

Sure. Thanks, Renee So yes, I think we've talked about for the last year or so we've really been putting I'd say an increased focus on the.

Speaker 9: Sure, thanks Renee. So, yes, I think we've talked about for the last year. So we've really been putting, I'd say, an increased focus on the, you know, the.

The adult segment, there and particularly as it pertains to the U S and the long term care setting where many of the adults with these conditions.

Speaker 9: adult segment there, and particularly as it pertains into U.S.

Speaker 9: reside, and we're seeing really nice growth there in that population and disproportionate to what we're seeing in the brand overall. So that is a nice growth driver. But across both the pediatric and adult market, there are, I'd say, three other things that are really driving the growth and I think speak well for the future. Renee mentioned the data. We've talked quite a bit with you about the data. We are sharing the data regarding combination with Clobazam and the beyond seizure benefits of Epidiolex, particularly as it relates to behavioral and…

And we're seeing really nice growth there in that population and disproportionate to what we're seeing in the brand overall, so that is a nice growth driver, but across both the pediatric and adult market. Yes, there I'd say three other things that are really driving the growth and I think speaks well for the future Rene mentioned the data we have.

Quite a bit with you about the data we are sharing the data.

Regarding combination of <unk> and the beyond theater benefits of Epidiorite, particularly as it relates to behavioral improvements in cognition improvements specifically, because we're trying to expand the definition of efficacy and really differentiate the brand from existing products today and I'd say both of these pieces of data really.

Speaker 9: of epidiolics, particularly as it relates to behavioral improvements and cognition improvements.

Speaker 9: Specifically because we're trying to expand the definition of efficacy and really differentiate the brand from existing products today. And I'd say both of these pieces of data really are eye opening and do a great job of that in the marketplace, particularly that beyond seizure data in the LGS and to evade space.

Our eye opening and do a great job of that.

In the marketplace, particularly that beyond seizure data in the lgs and Dravet space.

Speaker 9: And the third one is that we have done a really nice job, I think, over the last couple of years of expanding, I would say, or improving the quality of access to epidialics. You know, pretty much since launch, we've had a very high percentage of...

Third one is that we have done a really nice job I think over the last couple of years of expanding I would say are improving the quality of access to epidiorite pretty much for them. Since launch we had a very high percentage of commercial lives that have coverage as well as Medicaid lives at coverage for Epidiorite.

Speaker 9: Commercial lives that have coverage as well as Medicaid live that coverage for epidiotics, but what we've really seen in the last

What we've really seen in the last couple of year than this year in particular is that the quality of that coverage is improving in terms of the utilization management criteria are becoming less burdensome.

Speaker 9: A couple of years and this year in particular, is that the quality of that coverage is improving in terms of the utilization management criteria becoming less burdensome the utilization management criteria being broader in terms of providing easier access to epidiolics for a broad range of patients with refractory conditions and ultimately we're hearing from our customers feedback that they are finding it easier to get their patients

Pot and utilization management criteria being broader in terms of providing easier access to epidiorite for a broad range of patients with refractory conditions and ultimately we are hearing from our customers feel.

Feedback that they are finding it easier to get their patients on.

Speaker 9: on epidemics, which of course only reinforces, you know, their confidence in prescribing it. And then lastly, it, uh, a persistency has been really a hallmark of this brand since it was launched, you know, similar to activate once patients get through the early titration period. They tend to stay on epidemics for a long time, but despite this, we still have seen rooms for opportunity to invest.

Epidiorite, which of course, only re enforces their confidence and.

And prescribing it and then lastly at all at Persistency has been really a hallmark of this brand since it was launched similar to activate once patients get through the early titration period. They tend to stay on epidemics for a long time, but despite this we still see room for opportunity to invest.

Speaker 9: in improving that persistency, both at the beginning of the treatment and, you know, when patients have been on it for some time, and we're seeing nice improvements there, particularly if we can get, you know,

In improving that persistency, both at the beginning of the treatment and you know when patients have been on it for some time and we're seeing nice improvements there, particularly if we can get.

Speaker 9: ACPs to support patients and get them up through that titration period. Overall, we see them stay on the drug for a pretty long time. So lots of things there to point to as current and I think future growth drivers in the

ACP to support patients and get them up through that titration period overall, we see them stay on the drug for a pretty long time, so lots of things there to point to a current and I think future growth drivers in the U S.

Your next question comes from the line of our cash to worry from Jefferies. Please go ahead.

Speaker 1: Your next question comes from the line of Akash Tiwari from Jeffries. Please go ahead.

Speaker 14: Hi, thanks for taking our questions. This is Ivy on Prakash. So we have one quick question on our action. So you're getting to data for JVP 441 in health and volunteers by your end. I guess what level of MWT do you need to see to move this program forward? Also, what makes you feel comfortable about the liver talks profile? Thanks.

Hi, Thanks for taking our questions. This is ivy on harsh. So we have one quick question on <unk>. So you are guiding to data for GBP 441 in healthy volunteers by year end.

Guess what level of <unk> do you need to see to move. This program forward also what makes you feel comfortable about the liver tox profile. Thanks.

Sure So I'll take that one Bruce.

Yes. Please.

Yes so.

Speaker 11: Yeah, so, you know, we have certainly some benchmarks with other erection agonists that are in the clinic. So, in terms of what we'd be looking for in the Healthy Volunteer MWT study is, you know, comparable efficacy.

We have certainly some benchmarks with other.

Orexin agonist that are in the clinic. So in terms of what we'd be looking for.

The healthy volunteer <unk> studies comparable efficacy and I think that model translates pretty well.

Speaker 11: And I think that model translates pretty well into patients. And so we have the benefit of benchmarking across a range of doses that were evaluating versus other compounds, not only in the erecting class, but also other weight promoting agents. So I think we'll have a good sense of, you know, when we hit a level of FSC, that will confident move.

And to patients and so we have the benefit of benchmarking.

Across a range of doses that were evaluating.

Versus other other compounds not only in the Orexin class, but also other other wake promoting agents. So I think we will have a good sense of.

When we when we hit a level of efficacy that we're confident.

Moving forward with and then.

Speaker 11: And then, sorry, the second part of the question was.

Sorry, the second part of the question was.

Liver tox profile.

Yes, yes, yes.

Speaker 11: Yes, so we don't think the liver toxicity is a class effect and we think based on what has been said from the from the Takeda compound that it's likely to be related to that specific structural class. And so we've even at the time that we in license from Sumitomo we knew we were operating in a different chemical series and so we don't think any of that risk is carried over.

We don't think the liver toxicity of a class effect and we think based on what has been said from the from the Takeda compound that it's likely to be related to that specific structural.

And so we've.

Even at the time that we in licensed from Sumitomo. We knew we were operating in a different chemical series and so we don't think any of that risk is carried over.

Speaker 11: In our preclinical toxicology studies, there was no concern based on liver toxicity.

In our preclinical toxicology studies there was no.

CERN based on liver toxicity either.

Your next question comes from the line of David <unk> from Piper Sandler. Please go ahead.

Speaker 1: Your next question comes from the line of David Amselin from Piper Sandler. Please go ahead.

Speaker 11: Hey, thanks, so also had a question on.

Hey, Thanks. So also had a question on <unk>.

Speaker 11: the Eurexin Agnes-GZP441. So we've seen some early tolerability data at world sleep for the other

The erection agonist GBP 441, so we've seen some early tolerability data.

At World sleep for the other compounds.

Speaker 11: urinary urgency being one that comes to mind, also visual disturbance. I wanted to pick your brain on how you're thinking about those as, you know, being on target effects or is something else going on and just your general level of, you know,

Urinary urgency.

Being one that comes to mind also visual disturbance I wanted to pick your brain on.

How youre thinking about those as well.

Being.

On target effects or is something else going on and just your general level of.

I guess vigilance is the right word.

Speaker 11: I guess vigilance is the right word, on those kinds of AEs. Thanks.

Those kinds of Aes. Thanks.

Speaker 11: Yeah, so I mean, look, in the early days across these compounds, we have a lot to learn.

Yes, I mean listen the early days across these compounds. So we have a lot to learn.

Speaker 11: But I would say that therapeutic index is going to be very important, whether that be

I would say therapeutic index is going to be very important whether that be to what we perceive is on target effects like the urinary frequency that you mentioned or potential off target.

Speaker 11: to what we perceive as on-target effects, like the urinary frequency that you mentioned, or potential off-target, like hepatotoxicity. The therapeutic index is going to be important. Part of that may relate to the half-life of the compound. I mean, if you have something that...

Toxicity, the therapeutic index is going to be important part of that may relate to the half life of the compound I mean, if you have something that.

Speaker 11: is too long a half life you may see residual effects into the evenings causing even an thumbnail which is obviously counterproductive.

As to longer half life, you may see residual effects into the evenings, causing even in some there which is obviously counterproductive.

Speaker 11: from the therapeutic content. And so having a favorable half-life and being able to dose in a way that creates therapeutic index, you know, for either on target or any potential off target toxicity will be important. And that's part of what we're doing in our healthy volunteer studies, both of the healthy, both of the single dose as well as the multiple dose. It's really exploring the therapy.

From the therapeutic intent and so having a favorable half life and being able to dose in a way that creates therapeutic index.

For either.

Target or any potential off target toxicity will be important and thats part of what we're doing in our healthy volunteer studies both of the house.

The single dose as well as the multiple dose.

Exploring the therapeutic range.

Speaker 5: I'm very still seeing those things that will allow us to select them an optimal regiment to be evaluated in patient.

Various dosing.

Those things that will allow us to select them.

And optimal regimen to be evaluated in patients.

Your next question comes from the line of June Lee from <unk> Securities. Please go ahead.

Speaker 1: Your next question comes from the line of June Lee from Truist Security. Please go ahead.

Hi, This is Jeremy on for Jim Thanks for taking our questions. How are you looking at the Oxy b market evolving both in terms of evaluating Xyrem and has the EG impact been as expected.

Speaker 15: Hi, this is Jeremy on for June . Thanks for taking our questions. How are you looking at the OxyBeat market evolving, both in terms of XyWave and XyRAM? And has the EG impact been as expected? Thanks.

Yeah.

Speaker 6: Yeah, I'll start on that one and just say, again, the way things have played out this year has been very much in line with our expectations. You know, Xyrem has been declining.

Start.

On that one and just say again the way things have played out this year has been very much in line with our expectations.

Xyrem has been declining.

Speaker 6: for years now, largely because we've been successful as I wave, giving patients a health lifelong treatment options.

For years now.

Largely because we've been successful with XI ways, giving patients healthcare lifelong treatment option.

Speaker 6: That decline has continued this year, obviously complemented by having new entrants in the marketplace, but that revenue stream for us is now very small relative to our total business at about 16% of our revenues this quarter, if you add up Xyrem.

That decline has continued this year obviously.

Complemented by having new entrants in the marketplace.

But that.

Revenue stream for US is now a very small relative to our total business at about 16% of our revenues. This quarter, if you add up ziram.

Speaker 3: and our royalties on the AG. And we're focused on growing Zywave. We think the product has great durability as an asset. We are very excited about the opportunity to continue growing the idiopathic hypersomnia market. We know there are more patients to reach. We know diagnosis can improve.

And our royalties on the AG.

And we're focused on growing XI wave.

We think the product has.

Great durability is an asset we are very excited.

About the opportunity to continue growing media Patrick I for some <unk>.

Market. We know there are more patients to reach we know diagnosis can improve.

Speaker 6: And as physicians gain more experience using this product and seeing the benefit in their patients that mirrors what we saw in clinical trials.

And as physicians gain more experience using this product and seeing the benefit in their patients the mirrors, what we saw in clinical trials.

Speaker 6: You know, we think that's very favorable for their intended increase use of the product.

We think thats very favorable for their intended to increase use of the product.

Speaker 6: And we still think there's growth left in the narcolepsy market. We haven't seen much of a change in the overall growth dynamic since the Avidel launch, but it's usually true that having multiple companies out talking about...

And we still think there's growth left in the narcolepsy market, we haven't seen much of a change in the overall growth dynamics since the avatar launch, but it's usually true that having multiple companies are talking about.

Speaker 6: you know, a disease that is sometimes underdiagnosed can be helpful. So we're.

Hi.

A disease that is sometimes under diagnosed can be helpful. So we're.

Speaker 6: We're excited to continue to grow cy-

Hi.

We're excited to continue to grow sideways.

Speaker 1: Your next question comes from the line of Gary Notchman from Raymond James. Please go ahead.

Your next question comes from the line of Gary Nachman from Raymond James. Please go ahead.

Hi, good afternoon.

Speaker 16: Hi, good afternoon. First, can you talk about RILA's expanding in Europe and specifically your expectations on how much that product will contribute XUS over time? What's the reasonable target there? And then just on your point Bruce on Zywave in idiopathic hypersomnia, how concentrated is the current prescribing base? And what if some of your initiatives are trying to expand that further? And at what pace do you think you'll be able to do that to tap into more of those patients? Thanks.

First can you talk about Riley is expanding in Europe, and specifically your expectations on how much that product will contribute X U S over time, what's a reasonable target there.

And then just on your point Bruce on XI wave in idiopathic hypersomnia, how concentrated is the current prescribing base and what are some of your initiatives to try and expand that further and at what pace do you think youll be able to do that to tap into more of those patients. Thank you.

So two different questions maybe.

Speaker 6: So two different questions. Maybe I'll hit Zywave first and say the prescriber base for IH is very overlapping with the narcolepsy prescriber base, about 90%.

I'll hit XI wave first and say.

The prescriber base for IH is very overlapping with the narcolepsy prescriber base about 90%.

Speaker 6: You know, as you heard in our comments on the call, we are increasing our effort behind IH to have some folks focus on that, specifically get out to some physicians.

As you heard in our comments on the call we are increasing our effort behind IH to have.

Some folks focus on that specifically get out to some physicians.

Speaker 17: who may be a little less familiar with using Oxivate to support them, but the prescriber base is very similar. Renee, you want to talk about Rylase a little bit?

Who may be a little less familiar with using ox abate.

To support them.

The prescriber base is very similar Renee you want to talk about really is a little bit.

Yes, Im happy too. So we're really pleased to be able to make this product available in Europe and as we stated we expect to begin that rolling launch later this year I will stress that the market dynamics are very different in Europe versus the U S. So.

Speaker 4: Yeah, I'm happy to. So, we're really pleased to be able to make this product available in Europe , and as we stated, we expect to begin that rolling launch later this year. I will stress that the market dynamics are very different in Europe versus the U.S. So, in Europe , we have Erwin Ace on the market as a competitor. We have quite a different pricing scheme, and then certain steps to take.

In Europe, we have <unk> on the market as a competitor we have quite a different pricing scheme and then certain steps to take from a market access perspective to ensure that <unk> is secured on protocols, which which will take some time.

Speaker 4: from a market access perspective to ensure that in RILAce is secured on protocols, which will take some time. So taking all of these things in consideration, I would say being on the market in Europe will provide growth, but characterize that as relatively small and something that would be achieved over time, relative to the overall opportunity in the US.

All of these things in consideration.

I'd say being on the market in Europe will provide growth, but characterized that is relatively small.

And something that would be achieved over time relative to the overall opportunity in the U S.

Speaker 4: And then on the topic of the US maybe I'll turn to Kim to provide a few comments of what we're seeing there.

And then on the topic of the U S. Maybe I'll turn to Ken to provide a few comments of what we're seeing there.

Speaker 9: Oh, and I, I can do both.

And IHS pilots.

Both.

Speaker 18: On Riley. Yeah, I'm Riley. Okay, great. Thanks. I'm happy to do that. So, yeah, we're, you know, we continue to be, you know, just I'm very pleased with how this product is performed. You know, we never really had the opportunity to understand what the peak.

On Riley.

And relates to predict okay, great. Thanks, I'm happy to do that so yeah. We were we continue to be you know just.

I'm very pleased with how this product will perform you know we never really had the opportunity to understand what the peak of this market can be given it was supply constrained so.

Speaker 18: of this market to be given it was always supply constraints. So, you know, we obviously don't give products with the guidance we haven't talked about the peak. So we're, you know, just continuing to see strong demand which we think reflects significant.

Obviously, you don't give product specific guidance, we havent talked about the peak, but we're just continuing to see strong demand.

Which we think reflect significant patient need I think Rene mentioned in the presentation that some of the growth drivers, we've seen and the demand that's being driven was expected and some of it was a bit unexpected.

Speaker 18: patient need. I think René mentioned in the presentation that some of the growth drivers we've seen and the demand that's being driven was expected and some of it was a bit unexpected in this unsupply constrained market. You know, we did expect to see healthcare providers switching patients.

And in this untapped by constrained market, we did expect to see healthcare providers switching patients.

Speaker 18: you know, more rapidly due to, you know, hypersensitivity responses. But we are also seeing quite a bit of switching going on in terms of other types of treatment-related issues from E. coli-based asparaginase. In addition, you know, again, while we don't promote it that way, and we don't promote the product for first-line use, we are seeing, you know, a fair amount of first-line use based on the advantages of this product having a.

More rapidly due to you know a hypersensitivity responses. We are also seeing quite a bit of switching going on in terms of other types of treatment related issues from E coli based asparaginase and.

In addition, and again, while we don't promote it that way and we don't promote the product for first line use we are seeing.

A fair amount of first line use based on the advantages of this product having a board acting profile relative to current first line of spares and <unk> therapies and the concern that some providers happened, particularly in some ah patient populations like the adult patient population.

Speaker 18: Fort acting profile relative to current first line of spares and a therapies. And the concern that some providers have, in particular in some patient populations, like the adult patient population around, you know, the potential for treatment related issues. And then lastly, we've been seeing some really nice growth in the overall efforts we've made this year in the adolescent and young adult market. We're seeing this population starting to increase usage.

Around the potential for treatment related issues.

And then lastly, we've been seeing some really nice growth in the overall efforts. We've made this year in the adolescent and young adult market our.

This population is starting to increase usage in these patients and as I mentioned. This is one of the places where we see them using the product a little bit differently than we had originally anticipated. So overall the market has embraced it and especially in the pediatric market, where it's been adopted universally in.

Speaker 18: in these patients and you know as I mentioned this is one of the places where we see them using the products a little bit differently than we had originally anticipated. So overall the market has embraced it especially in the pediatric market where it's been adopted universally in pediatric protocols but really seeing you know increased usage of Erwinia based asparagus amazes in the adolescent and young adult markets of bribes.

Eric protocols, but really seeing increased usage of.

Or what do you based asparaginase in the adolescent and young adult market for Brian Lee.

Your next question comes from the line of Gregory <unk> from RBC capital markets. Please go ahead.

Speaker 1: Your next question comes from the line of Gregory Renza from RBC Capital Markets. Please go ahead.

Hey, good evening, Bruce and team congrats on the update and thanks for taking my question.

Speaker 19: Hey, good evening, Bruce and Tima. Congrats on the update and thanks for taking my question. Bruce, maybe just a more specific one on the competitive dynamics of Oxibit that you...

Bruce maybe just a more specific one on the competitive dynamics of oxalate that you've described.

Turning just curious how you would put into context, the value or maybe the value lost.

That I assume right that <unk> patient, yes that is how important is that patient has tried Brian riser was trying them rise and the corresponding prescriber, how important that patient to that to the market strategy that that Renee laid out would you see if anything an opportunity to capture or maybe recapture such patients says that option.

Speaker 19: and the corresponding prescriber, how important is that patient to the market strategy that that were named laid out in?

Established in the marketplace. Thanks again.

Speaker 17: Yeah, I love the way you ended your question, which is right where I was gonna go with my answer, which is we absolutely expect a new product to get some use. But we think all high sodium...

Yes, I love the way you ended your question, which is right where I was going to go with my answer which is we absolutely expect a new product to get some use.

But we think all high sodium.

Speaker 17: patients, be they on Xyrem, AG Xyrem, or the Lumerize product.

Patients be they on Xyrem.

Xyrem or the <unk> product.

Speaker 17: our potential future XI wave.

Our potential future XI wave.

Okay.

Speaker 17: You know, as we saw from the data we shared earlier this year, but the

As we saw from the data we shared earlier this year.

Neurology meeting.

Speaker 17: We can see even in as little as 180 days an increase in hypertension diagnosis or initiation of antihypertensive therapy when starting on a high sodium oximate product. You know as physicians and patients have already discovered this matters.

We can see even in as little as 180 days an increase.

In hypertension diagnosis or initiation of anti hypertensive therapy, when starting on a high oximeter high sodium ox debate.

So.

As physicians and patients have already discovered this matters and we believe that will continue to be important making sideways the oxidative choice.

Speaker 6: We believe that will continue to be important, making ZyWave the optimative choice.

Your next question comes from the line of Charles Duncan from Cantor Fitzgerald. Please go ahead.

Speaker 1: Your next question comes from the line of Charles Duncan from Cantor Fitzgerald. Please go ahead.

Hi, This is lane Kim on for Charles Congrats on the quarter and thank you for taking our questions.

Speaker 20: Hi, this is the link in the info for Charles. Congrats on the quarter and thank you for taking our

Speaker 20: Regarding PTSD, what are your perspectives on the unmet need and the potential for psychedelic?

PTSD what are your perspective on the unmet need and the potential for psychedelic medicine, such as maps MD&A and possibly campuses. The last item based therapy, and where do you see GBP 150, <unk> fitting in the emerging treatment landscape. Thank you.

Speaker 20: such as maps and DNA and possibly compasses, silicidin B.

Speaker 20: And where do you see JCP 150 fitting in the emerging treatment landscape? Thank you.

Rob do you want to jump in on that.

Sure.

Speaker 11: Sure, so what I think about a treatment like MDMA and what is associated with that, terms of the support that one needs, ultimately I think that that's gonna be appropriate for a subset of the population. PTSD is overall very, very common. And so we think the HTTP 150 could potentially be much more, broadly applicable.

When I think about treatment like MDMA and what is associated with that in terms of support that one needs. Ultimately I think that that's going to be appropriate for a subset of the population.

TSB has over overall very very common.

And so we think ACP FIFO could potentially be much more broadly applicable.

Your next question comes from the line of Jeff Hung from Morgan Stanley. Please go ahead.

Speaker 1: Your next question comes from the line of Jeff Hung from Morgan Stanley . Please go ahead.

Speaker 21: Thanks for taking my question. For the subicalidomyide here, what's the bar for success in the essential tremor study? And can you talk about what gives you confidence that the phase IIb will read out positively? Thanks.

Thanks for taking my question <unk> sure what's the bar for success in essential Tremor study and can you talk about what gives you confidence that the <unk> will read out positively.

Yes, I think we have a good sense of.

Speaker 11: Yeah, I think they have a good sense of, yeah, I think we have a good sense of what's the meaningful change on the Tetris endpoints and more focus on the ADL and the subset of the performance scale as well. And so from our phase two and from the interactions with K wells and FDA, we have a good sense of what's, you know, what's going to be a meaningful change there. And you've seen the other studies that have been published, you know, that could be. Relatives.

Yes.

I think we have a good sense of what's the meaningful change on the Tetris pinpoints and more focused on the ADL in a subset of the performance scale as well.

And so from our phase two and from interactions with Kols in FCA, we have a good sense of what's what's going to be a meaningful change there and you've seen the other studies.

There could be.

Relative benchmarks why do we think that GBP three five is differentiated in a couple of things one is that as the state dependent inhibitor. So selectively acts on active ion channels.

Speaker 5: You know, why do we think that JCP385 is differentiated? Well, a couple of things.

Speaker 11: One is that it's a state-dependent inhibitor, so it selectively acts on active ion channels.

Speaker 11: which should ultimately create a better therapeutic index.

Ultimately create a better therapeutic index, we have a once daily formulation and based on our prior studies, we selected three fold dose range for the phase <unk> 10, 20, and 30 milligrams.

Speaker 11: We have a once daily formulation and based on our prior studies, we selected threefold dose range for the phase 2B, 10, 20 and 30 milligrams, which I think is really allowed us to kind of push that dosing and expose your up to really get maximal.

I think has really allowed us to kind of push that.

Dosing and exposure up to really get maximal efficacy. So we think it's differentiated.

Speaker 11: So we think it's differentiated on that basis and, you know, hope to see pretty robust efficacy across that dose.

On that basis.

And.

Hope to see.

Pretty robust efficacy with cross that dose range.

Your next question comes from the line of Mohit Bansal from Wells Fargo. Please go ahead.

Speaker 1: Your next question comes from the line of Mohit Bansal from Wells Fargo. Please go ahead.

Great. Thanks for taking my question.

Speaker 22: Great, thanks for taking my question. So I have a question regarding Docs with Franchise.

I have I have a question regarding box with franchise.

So can you comment on if there is anything going on with the price single sided with the with loom ryzen and trade generics on the market.

Speaker 22: So can you comment on if there is anything going on with the pricing of PsyWave, with Lumerize and Oxide Genetics on the market? I'm asking because this is probably the first time since the launch of AGs, we have seen a sequential decline in this franchise. So just want to understand how do you see growth to get to the two billion number that you talked about in 2025? Thank you.

I'm asking because this is probably the first time since the launch of <unk>, we have seen a sequential decline in this franchise.

So just wanted to understand how do you see growth to get to the 2 billion number that you had talked about in 2025. Thank you.

Speaker 8: Uh, so the the quick answer on pricing is there has not been a significant, uh change in terms of

So the quick answer on pricing is there has not been a significant change in terms of <unk>.

Speaker 8: sort of our revenue per patient in the past few quarters. In terms of the revenue decline, that's driven by

Our revenue per patient in the past few quarters.

In terms of the revenue decline that's driven by <unk>.

Speaker 8: loss of Xyrem revenues, which as I've said, have been going down for a long time, and are now representing a smaller and smaller portion of our overall revenues while Xywave continues to grow. So those two things at present, as we're built into our guidance for the year, you know, essentially, are offsetting each other to some degree, but, you know, our focus is on growing that Xywave.

Loss of Xyrem revenues, which as I've said have been going down for a long time.

And are now representing a smaller and smaller portion of our overall revenues while XI wave continues to grow so those two things at present as it was built into our guidance for the year.

Essentially are offsetting each other to some degree but.

Our focus is on on growing that sideways.

Speaker 8: business in narcolepsy and importantly in India pathica prasamnia Even as we see royalty and come off the AG continue to increase

Business in narcolepsy, and importantly, an idiopathic hypersomnia.

Even as we see royalty income off the AG continue to increase.

Speaker 1: Your next question comes from the line of Troy a Langford from TD Cowan. Please go ahead.

Your next question comes from the line of Troy Langford from TD Cowen. Please go ahead.

Speaker 23: Hi, I'm Greta and I'm a progress in the corridor and thanks for taking our questions. Just with respect to the opportunity with the Vanna Data Mab, I guess what else you think you need to check off that list before you can complete the regulatory submission for the product in H124 or H126 here. And relate to that. Do you all think that you would need to significantly amplify your current oncology sales force to effectively commercialize the product?

Hey, congrats on all the progress in the quarter and thanks for taking our questions.

Just with respect to the opportunity of Amantadine I Mab.

I guess what else do you think you need to check off that list before you can complete the regulatory submission for the product in <unk> hundred 20 for next year.

And related to that do you think that you would need to significantly amplify your current oncology sales force to effectively commercialize the product.

Correct.

Yeah, I'll jump in on that one and just make some comments about our level of excitement about Danny and then ask Rob to comment on the path forward from a regulatory perspective, so as we mentioned on the call. We are extremely excited about this opportunity. This is a highly <unk>.

Speaker 4: Yeah, I'll jump in on that one and just make some comments about our level of excitement about Zannie and then ask Rob to comment on the path forward from.

Speaker 4: a regulatory perspective. So as we mentioned on the call, we are extremely excited about this opportunity. This is a highly derisked asset, a global asset for us, and then also one with significant revenue potential. We talked a bit about

Risked asset a global asset for US and then also one with significant revenue potential we talked a bit about.

Speaker 4: The data that's been generated to date since doing this transaction, we continue to be impressed with what we're seeing in terms of just robust antitumor activity in HER2. And that's in both monotherapy and in combination with other agents. And that gives us a ton of confidence to put both significant investment behind the molecule, but then also to outline the opportunity as having.

The data that's been generated to date since doing this transaction, we continue to be impressed with what we're seeing in terms of just robust anti tumor activity in her two and that's in both monotherapy and in combination with other agents and that gives us a ton of confidence to put both significant.

<unk> behind the molecule, but then also to outline the opportunity as having peak revenue potential of over $2 billion in terms of the near term a need from a commercialization perspective.

Speaker 4: peak revenue potential of over $2 billion. In terms of the near-term need from a commercialization perspective, we don't believe that this is going to require significant augmenting of our current field force. We believe that that will be quite efficient.

We don't believe that this is going to require significant augmenting of our current field force, we believe that that will be quite efficient.

Speaker 4: And of course, we are focused on going to market first with BTC, as Rob outlined, and then we'll build from there. So Rob, you want to comment on development?

And of course, we are focused on going to market first with BTC as Rob outlined and then we'll build from there. So Rob you want to comment on development.

Yes, I think the specific question was what else is needed to complete the BLA submission for <unk>.

Speaker 11: Yeah, I think the specific question was what else is needed to complete the BLA submission for BTC. And it's just the usual components. As you might expect, some of those components are going to be available sooner than others. And with breakthrough designation, we've been given the opportunity to do a rolling submission. That allows us to submit components as soon as they're ready to give the FDA sort of a head start on reviewing those components.

PTC and its just the usual components.

As you might expect some of those components are going to be available sooner.

Than others and with breakthrough designation, we have been given the opportunity to do a rolling submission that allows us to submit.

Components as soon as they're ready to go.

The FCA sort of a head start on reviewing those components.

Speaker 15: And then, as we said, within the first half of the year, expect to be able to provide everything that's needed to complete that submission.

And then as we said.

Within the first half of the year expected to be able to provide everything that's needed to complete that submission.

And we have no further questions in our queue. At this time I will now turn the call over to Bruce for closing remarks.

Speaker 1: You'll we have no further questions in our queue at this time. I will now turn the call over to Bruce for closing remarks.

Speaker 8: Thank you so much. I'd like to close today's call by recognizing our CHAS colleagues for their efforts in delivering new therapeutic options to patients, and also thank our partners and shareholders for their continued confidence and support. Thank you all for joining us today.

Thank you so much I would like to close today's call by recognizing our colleagues for their efforts in delivering new therapeutic options to patients and also thank our partners and shareholders for their continued confidence and support. Thank you all for joining us today.

Speaker 1: This concludes today's conference call. Thank you for your participation and you may now disconnect.

This concludes today's conference call. Thank you for your participation and you may now disconnect.

[music].

Uh huh.