Jazz Pharmaceuticals Q2 2023 Earnings Call Transcript

Quartr
Provided by Quartr
August 9, 2023

There are 16 speakers on the call.

Operator

Afternoon, and thank you for attending the Jazz Pharmaceuticals Second Quarter 2023 Financial Results Call. My name is Elisa, and I will be your moderator for today's call. All lines will be muted during the presentation portion of the call with an opportunity for questions and answers at the end. I would now like to pass the call over to the Jazz Pharmaceuticals team. You may proceed.

Speaker 1

Thank you, operator, and good afternoon, everyone. Today, JAS Pharmaceuticals reported its Q2 2023 financial results. The slide presentation accompanying this webcast is available on the Investors section of our website. Investors may also refer to the press release we issued earlier today, which is also posted to our website. On the call today are Bruce Kozad, Chairman and Chief Executive Officer Rene Galat, Executive Vice President and Chief Financial Officer Dan Swisher, President and Chief Operating Officer and Rob Unone, Executive Vice President, Global Head of R and D Kim Sablich, Executive Vice President and General Manager, United States, will join the team for Q and A.

Speaker 1

On Slide 2, I'd like and results, which involve risks and uncertainties that could cause actual events, performance and results to differ materially from those contained in these forward looking statements. We encourage you to review the statements contained in today's press release, in our slide deck and 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 We undertake no duty or obligation to update our forward looking statements. Turning to Slide 3 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.

Speaker 1

I'll now turn the call over to Bruce.

Speaker 2

Thanks, Andrea. Good afternoon, everyone, and thank you for joining us today. I'll start on Slide 5. In the Q2 of 2023, we once again delivered strong commercial results, advanced our efforts to unlock the tremendous potential of our pipeline and built on our record of driving operational excellence. In particular, our results in the second quarter highlight the durability and growth potential of our commercial portfolio, the capabilities and productivity of our R and D efforts and our focus on operational excellence.

Speaker 2

We are pleased to report strong execution across our commercial portfolio with all three key growth drivers of our commercial business, Cywave, Epidiolex and Rhylase achieving year over year double digit growth. Zywave grew by 39% in the 2nd quarter compared to the same period last year and is annualizing at well over $1,000,000,000 in revenue. Cywave continues to be the oxybate of choice and the only approved therapy for idiopathic hypersomnia. We expect our oxybate franchise to contribute 2,000,000,000 of the $5,000,000,000 in total revenue component of Vision 2025 and are well positioned to reach this target. As a reminder, our 2023 neuroscience revenue guidance, which we are raising at the midpoint today and Vision 2025, Both account for the availability of high sodium oxybate authorized generics or AGs and branded fixed dose high sodium oxybate.

Speaker 2

Epidiolex growth remains strong and we are confident in its potential to reach blockbuster status. We achieved double digit net sales growth in 2Q 2023 compared to the same period last year as we continue to drive prescriber growth across our global markets. Our launch in Europe is gaining momentum with additional international launches and indication expansions expected this year. In oncology, Rylase has continued to grow in the U. S.

Speaker 2

Underpinned by strong demand and our increasing emphasis on the adolescent and young adult market. Moving to our pipeline, given the level of productivity in our R and D organization, I'm going to call out just a few items. Rob will cover our R and D progress in more detail later in the call. Our pipeline continues to advance towards meaningful catalysts with the potential for as many as 4 late stage data readouts through 2024. The first being JCP-one hundred and fifty late this year, followed by suvacaltamide and Zanidatumab in GEA next year and top line PFS for Zepzelka in combination with Tecentriq in first line extensive stage small cell lung cancer at the end of 2024 or early 2025.

Speaker 2

In addition to its strong commercial performance in the U. S, we are extremely pleased that we recently received a positive CHMP opinion on our marketing authorization application for JCB-four fifty eight marketed as Rylase in the U. S. And expect European Commission approval later this year. Since we added zanidatumab to our pipeline last year, it has continued to impress and we're excited by its broad applicability, which we believe represents $2,000,000,000 plus in peak sales potential.

Speaker 2

Positive pivotal data from our Phase 2b trial In biliary tract cancers or BTC were featured in an oral session at this year's ASCO conference and concurrently published in The Lancet Oncology. These data were also selected for the best of ASCO meeting. Top line data readout from the ongoing Phase 3 gastroesophageal adenocarcinoma or GEA trial is expected in 2024. I'm also pleased to report that we recently received IND clearance For JZP-eight ninety eight, an engineered interferon alpha cytokine prodrug that is activated specifically within the tumor microenvironment 2nd quarter. Our commercial execution, coupled with our focus on operational excellence, has put us in a strong financial position, enabling us to execute a focused capital allocation strategy to invest in the products, pipeline programs and corporate development opportunities with the highest potential to deliver sustainable growth and enhanced value.

Speaker 2

Given our financial strength and our current stock price, we have resumed share repurchases under our existing program, which Renee will expand upon shortly. Based on our performance in the first half of twenty twenty three and expectations for the remainder of the year, We are raising our full year financial guidance for 2023. And longer term, we believe we are well positioned to achieve Vision 2025. Renee will provide additional commentary on our financials and guidance later in the call. Turning to Slide 6.

Speaker 2

We are excited about the progress we've achieved in the Q2 and believe it has substantially advanced us in all three areas of Vision 2025 and we are well positioned to achieve these important milestones in our transformation to a high growth global biopharma leader. I'll now turn the call over to Dan to review our commercial performance, after which Rob will share an update on our R and D progress, Renee will provide a financial overview and then we'll open the call to Q and A. Dan?

Speaker 3

Thanks, Bruce. I'm excited to provide an update on our commercial progress. Starting on Slide 8, with neuroscience and oxybate, we remain confident And the strength and durability of our oxybate franchises, Zywave continues to be the oxybate of choice and the only approved therapy for IH. Zywave revenues were $327,000,000 for the Q2 of 2023, representing growth of 39% compared to the same period in 2022. I'll note this growth was against the backdrop of high sodium oxybate competition Entering the market in January of this year.

Speaker 3

In narcolepsy, our focus remains on educating patients and prescribers on the benefits of reducing sodium intake. And this message continues to resonate. In addition to health benefits of lower sodium, based on our discussions with healthcare professionals and experienced 2,200 active patients taking XYOSTED patients taking XYOSTED for treatment of IH exiting the 2nd quarter. IH is a 24 hour sleep disorder. Despite sleeping a normal or longer than normal amount of time each night, People with IH may still experience debilitating symptoms during the day.

Speaker 3

Diwave is the 1st and only treatment approved by FDA to treat the full condition of IH. We are focused on educating prescribers on the importance of proper diagnosis and identifying appropriate patients who can benefit from XY Wave therapy. And a survey of sleep specialists indicated that 70% anticipate increasing their prescribing in the next 6 months. With regard to the average number of patients on XY Wave exiting the quarter, there was an operational change Pharmacy, which caused delays in getting refills on time for some Zywave patients. This has been addressed And importantly, overall, 2nd quarter XYOST HCP and patient demand were in line with our expectations in prior quarters.

Speaker 3

As Renee will review in more detail, we have raised our neuroscience revenue guidance at the midpoint, reflecting our continued confidence in the growth opportunity for And the durability of oxibate. Total revenues for the combined oxibate business, including royalties from a high sodium oxybate AG Decreased 2% to $492,000,000 in the 2nd quarter compared to the same period in 2022. There were approximately 16,200 total average active Jazz Oxivate patients In the Q2, a decrease compared to the end of the Q1, primarily reflecting the expected impact of Xyrem As a result of the availability of a high sodium oxybate AG, our focus is on continuing to grow low sodium XY Wave across both narcolepsy and IH, We are pleased with Zywave's growth across both indications, even as additional high sodium oxybate competition is available for patients with narcolepsy. The continued growth of Zywave is one of the factors that contributed to our increased 2023 neuroscience revenue guidance. And as Bruce mentioned, we are well positioned to achieve our vision 2025 target of $2,000,000,000 in revenue from our Oxivate franchise.

Speaker 3

Slide 9 highlights the compelling low study on health benefits we are sharing with healthcare professionals and patients. As narcolepsy is a debilitating chronic condition, We have focused on educational efforts around the lifelong burden of high sodium intake for narcolepsy patients. We live with a 2 to 3 times higher risk than the general population of cardiovascular comorbidities such as stroke and heart failure. XYWAY is the only approved low sodium oxybate and the only oxidate without a labeled warning about high sodium intake As 92% less sodium than high sodium oxidates, the American Heart Association recommends a maximum of 1500 milligrams of sodium per day. While high sodium AGs and branded oxalates of 1100 to 1640 Milligrams of sodium.

Speaker 3

XY Wave has only 100 to 140 milligrams, a reduction of 1,000 to 1500 milligrams of sodium per day. To put this in perspective, it would take 12 years of treatment with Zywave to equal the sodium intake of 1 year of high sodium oxybate treatment. This has significant potential health benefits including lower blood pressure and improved cardiovascular health. To add to the literature on sodium impact, we presented data at this year's American Academy of Neurology meeting That showed narcolepsy patients treated with high sodium oxybate at 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 oxybate. In fact, the risk of those taking high sodium oxybate was Twice that of the CONTROL group.

Speaker 3

We believe these data highlight that sodium intake is a health concern for all narcolepsy patients and one that can have near term consequences. FDA has recognized that the difference in sodium content between XY Wave And high sodium oxybates including Xyrem, AG Xyrem and lumeride is likely to be clinically meaningful in all patients with narcolepsy And that XYOSTED is safer in all such patients. Lumerise is the recently launched branded fixed dose high sodium oxidate that has the same sodium content as Xyrem. We believe that the majority of patients and healthcare providers will continue to prioritize long term health With respect to competition from high sodium oxybate authorized generics or AGs, Amneal announced the launch of their AG in early July. 2 additional companies, Lupin and Parr Also have rights to launch an AG product.

Speaker 3

At this time, PAR and Lupin have elected not to launch. These 3 AG suppliers are each restricted to a low single digit percentage of Xyrem sales volume. As a reminder, earlier this year, Hikma launched the volume unlimited AG. Jazz receives meaningful royalties on all high sodium oxybate AGs. Moving to Slide 10, we remain confident in the blockbuster potential of Epidiolex with yet another quarter of double digit year over year revenue growth.

Speaker 3

Net product sales increased 15% to $202,000,000 in the 2nd quarter compared to the same period in 2022, driven by underlying demand. We have seen increased penetration in the long term care setting, driven by additional in person engagement with physicians And we have additional opportunities for growth. Turning to Slide 11, we are focused on multiple opportunities to drive Epidiolex to blockbuster status. We continue to see a positive impact from our educational efforts focused on optimal dosing and caregiver reported comes beyond seizure control from the BECOME survey, which further differentiates Epidiolex from other anti seizure medicines. In particular, reports from the field indicate that the BECOME data has been very impactful with both HCPs and caregivers.

Speaker 3

The compelling clinical data regarding the use of Epidiolex in combination with clobazam versus using the agents individually continues to resonate. Our commercial team also has an enhanced focus on further penetration into the adult setting. We are also pleased our commercialization efforts outside the U. S. Continue to gain momentum.

Speaker 3

Slide 12 illustrates our progress in expanding Epidiolex Outside of the U. S, Epidiolex is now launched and reimbursed in 23 countries around the world, including all 5 key European markets. While it's early, we are very encouraged by initial uptake in these markets with favorable pricing and access. We anticipate additional reimbursement decisions and submissions through this year and next. Moving to our oncology franchise beginning on Slide 13, net product sales for Rylix were $102,000,000 for the 2nd quarter, A 39% increase year over year and our 4th consecutive quarter of growth.

Speaker 3

We continue to see strong demand for Rylase, reflecting the significant unmet patient need for a high quality reliable supply of erwinia asparaginase for patients with acute lymphoblastic leukemia. Based on the availability of Rylaith, healthcare professionals have indicated they are returning the best clinical practice in switching therapy at the first signs of hyper We continue to receive positive feedback from healthcare providers about the adoption of the Monday, Wednesday, Friday dosing regimen, which allows a dosing schedule that is more in line with preferred clinical practice. RILACE has been almost universally adopted in pediatric oncology protocols and we are encouraged to see that there is increasing use of RILACE And the treatment of adolescents and young adults for the AYA market, which is an area of increased emphasis for us in 2023. Outside of the U. S, we recently received a positive CHMP opinion.

Speaker 3

With the positive opinion granted, we anticipate EC approval of our MAA submission later this year. Regarding the market opportunity, I'll note that there is competition in many European markets. Jazz has consistently delivered a reliable high quality supply of this important therapy in the U. S. And we are excited for patients and healthcare Turning to Slide 14, we rapidly established Zepsilka as a treatment of choice in second line small cell lung cancer.

Speaker 3

Net product sales increased 3% to $70,000,000 in the Q2 compared to the same period in 2022. We have achieved significant penetration in the 2nd line setting, but there remains significant unmet need for patients diagnosed with small cell lung cancer The 5 year overall survival rates of less than 10% and median overall survival of 6 to 24 months depending on the stage of diagnosis. Given this prognosis, there is a further opportunity to both improve patient lives and drive growth through our pivotal Phase 3 trial And first line small cell lung cancer in combination with Tecentriq, we expect top line PFS data readout at the end of 2024 or early 2025. In the U. S, there are approximately 27,000 first line Small cell lung cancer patients treated annually.

Speaker 3

Dabcelka has the potential to increase the duration of response with these earlier stage patients. With that, I'll turn it over to Rob for an update on our pipeline and upcoming milestones. Rob?

Speaker 4

Thanks, Dan. Starting on Slide 16, we provided an overview of the key clinical programs in our diversified pipeline. We are excited about the advances we've made so far this year with the potential for as many as 4 late stage data readouts Through 2023 2024, which include JZP-one hundred and fifty in PTSD, suvacalcomide in central tremor, savadatimab in GEA and sepselka in combination with Tecentriq in first line small cell lung cancer. I'll discuss a few of our programs in more detail shortly, but I wanted to broadly highlight our progress across the pipeline before moving on. Starting with neuroscience, we expect top line data from our Phase 2 trial of JZP-one hundred and fifty in PTSD by the end of the year.

Speaker 4

For JZP-four forty one, our rexin-two receptor agonist that has the potential to treat narcolepsy, IH and other sleep disorders, we anticipate initial proof of concept in healthy volunteers later this year. In addition, We have ongoing trials for suvacalcomide in both central tremor or ET and Parkinson's disease tremor. The top line data from the ET trial expected in the first half of twenty twenty four. Moving to oncology, Zanadatimab is a priority program for us. We aim to advance Zanadatimab to the market as rapidly as possible with 2nd line BTC representing our first potential commercial indication.

Speaker 4

We are planning for a potentially accelerated approval of zanodetimab And second line BTC and have alignment with the FDA on a confirmatory trial in first line metastatic BTC where there remains unmet patient needs. We are also evaluating XANI in GEA, breast cancer and other HER2 positive solid tumors. For ZYSLCA, we expect top line PFS Data readout at the end of 2024 or early 2025. Small cell lung cancer patients have particularly poor outcomes with a 5 year overall survival rate of less than 10%. Currently, Zevzelka has indicated to treat patients in the second line setting, We see a clear mechanistic rationale for Zetzelka to potentially benefit more patients and increase the duration of response in the first line setting as maintenance therapy in combination with the standard of care.

Speaker 4

Beyond small cell lung cancer, We have elected to close our Phase 2 basket trial based on limited responses in 3 solid tumor cohorts. We're analyzing the findings from that trial and continue to explore additional tumor types that may benefit from treatment with Xvelka. As Dan and Bruce mentioned earlier, we are very pleased to have received a positive CHMP opinion on JZP-four fifty eight, which is marketed as Rylase in the U. S. With Monday, Wednesday, Friday and every 48 hour dosing regimens as well as IB and I'm administration.

Speaker 4

We anticipate EC approval later this year. Moving to Slide 17, I'll expand on my earlier comments regarding Zanadatimab. Enadetimab is a novel bispecific antibody that can simultaneously bind 2 non overlapping epitopes of HER2 noted by paratopic binding. This unique design results in multiple mechanisms of action, including dual HER2 signal blockade, Receptor clustering on the cell surface leading to internalization by bipyratopic binding and potent immune effector functions, including antibody dependent cellular cytotoxicity, antibody dependent cellular phagocytosis And complement dependent cytotoxicity, leading to encouraging anti tumor activity in patients. Pamadatamab has shown compelling activity across a broad range of HER2 positive tumors and we presented promising efficacy Early survival data at both ASCO and ASCO GI this year.

Speaker 4

Additional data presentations are planned for later this year, including quality of life outcomes from the Horizon BTC-one pivotal study at the European Society of Medical Oncology Annual Congress. This slide speaks to our development strategy presented, which is focused on 4 key areas. First, target areas with no approved HER2 agents, such as the significant unmet need second line HER2 positive BTC as well as other solid tumors. 2nd, maximize the opportunity in TEA and other HER2 positive tumors where we believe zamidatamab Has the potential to be the HER2 targeted treatment of choice, supplanting current HER2 targeted agents. Compelling data has demonstrated that vamadetumab has the potential to be a foundational treatment for patients with HER2 positive GEA.

Speaker 4

3rd, we see substantial opportunity in settings where zamizantinumab could be used in combination with standard of care for other novel therapies, particularly in breast cancer and in earlier lines of treatment. 4th, we plan to build upon the compelling activity We've seen across a broad range of HER2 positive tumors to address the patient need in additional

Speaker 3

tumor types.

Speaker 4

On Slide 18, I want to provide more insight into our excitement about the long term potentials out of Datamax, which we believe could go beyond addressing significant unmet needs in BTC and GEA to include breast cancer as well as multiple additional cancers that Overexpress HER2. With the potential to transform the current standard of care in multiple HER2 positive cancers, We are committed to rapidly advancing and expanding our development program. We believe that savadimab has the opportunity to be a differentiated bispecific treatment of choice for HER2 positive cancers. We expect to enter the market 1st and second line BTC, where physicians will gain important experience with emodatimab. The approach is supported by compelling data presented at ASCO in previously treated HER2 positive BTC.

Speaker 4

We are pleased to share that we are planning for potential accelerated approval of zanodetimab in second line BTC Based on the Horizon BTC-one data and are working to rapidly bring this therapy to patients in critical need. We shared the impressive second line data with the FDA and have alignment on a confirmatory trial in first line metastatic DTC, where there remains an important unmet patient need. We are continuing to work with FDA regarding timelines And as our conversations progress, we will expect to be able to provide further updates. Following market entry and VTC, We expect to have a path to approval in first line GEA for the supplemental BLA submission, which provides a more streamlined approval process compared to a full BLA. With the treatment landscape evolving Following recent data readouts, we continue to strongly believe that substantial opportunity remains To address the unmet patient need to first line TEA, including the HER2 positive PD L1 negative patient population, where the standard of care remains trastuzumab plus chemotherapy.

Speaker 4

For patients who are PD L1 positive, We continue to believe that zanodetimab has the potential to be the HER2 targeted treatment of choice, while also combining with BeiGene tislelizumab in order to treat those who are eligible to receive anti PD-one therapy at GEA. Further, there remains an opportunity to move into earlier stages of GEA

Speaker 5

where we see the

Speaker 4

potential to help those patients prior to the metastatic setting in the neoadjuvant and adjuvant settings. GEA represents a significantly Larger patient opportunity compared to BTC and a prior approval in BTC We look forward to additional data From the ongoing pivotal Phase 3 GEA trial, Horizon GEA-one, expected to read out in 2024, which may support U. S. And global regulatory submissions. Breast cancer also represents a considerable opportunity Supported by promising early data as monotherapy in multiple combinations and across lines of therapy, Based on the efficacy and safety seen in studies to date, we believe zanodatamab is well suited for early stage disease, including potential use of neoadjuvant and adjuvant therapy.

Speaker 4

Further, we believe there is potential to help patients Previously treated with trastuzumabderoxetate or TDxD or for those patients were ineligible to receive treatment with TDXD. Dinadamab has also shown promise in HER2 positive and hormone receptor positive breast cancer as part of a novel combination. Supporting this, we have ongoing trials in neoadjuvant breast cancer and the opportunity to expand into both combination regimens and later lines of therapy in HER2 positive and HER2 HR positive breast cancer. We are also evaluating zanodetimab through multiple Earlier stage trials in other tumor types where few HER2 targeted treatment options are available. Navadetumab has shown clinical activity across a diverse set of HER2 positive indications such as colorectal cancer, non small cell lung cancer and multiple other cancers where there remain few targeted treatment options available to patients.

Speaker 4

Turning to Slide 19, I would like to highlight JZP-one hundred and fifty, our novel highly selective fatty acid amide Hydrolase or FAW inhibitor is currently in clinical development for the potential treatment of PTSD with Phase 2 top line data expected later this year. PTSD is a psychiatric disorder that affects millions of people and patients frequently have uncontrolled symptoms that impact their ability to perform activities of daily living and function socially. Only 2 antidepressants have received approval from FDA for the treatment of PTSD symptoms in the past 20 years. Current first line pharmacological treatment for PTSD Such as selective serotonin reuptake inhibitors mitigate some symptoms of PTSD, but are not designed to address the core underlying problem, fear extinction learning and its consolidation. Response rates to existing pharmacological treatments We have been granted FDA Fast Track for JZP-one hundred and fifty, underscoring the significant unmet needs of PTSD patients.

Speaker 4

JZP-one hundred and fifty is a once daily oral medication that has the potential to impact the pathophysiology and symptoms of PTSD. Data to date have demonstrated benefits of fear extension and stress response in healthy volunteers. Slide 20 shows the PTSD pathophysiology and JZP-one hundred and fifty's mechanism of action and treatment rationale. PTSD can result from direct or indirect exposure to traumatic experiences and events. Individuals with PTSD have intense and disturbing thoughts and feelings related to their experience that persist long after the traumatic event and they may relive the event through flashbacks or nightmares and feel sadness, fear, anger and detachment from other people.

Speaker 4

In PTSD, fear extinction deficits contribute to the persistence of traumatic memories. Interventions to promote fear extinction learning are a foundation of PTSD treatment. Preclinical and clinical data Indicates that exposure to stress and anxiety is associated with activation of fatty acid pumylhydrolase or FOG. Inhibition of Fau has the potential to directly target pathophysiological processes of PTSD. FAS is the enzyme responsible for the degradation of anandamide.

Speaker 4

Anandamide is reduced in PTSD And failure of anandamide to return to normal levels can result in a number of behavioral conditions underlying PTSD, including increased anxiety and impaired extinction processing of emotional memory. Inhibition of PHAR results and an increase in anandamide. This has been shown to reduce anxiety, improve fear extinction and recall and improved sleep architecture and self reported sleep quality. JZP-one hundred and fifty is a potent, highly selective Moving to Slide 21, we have outlined the design of the Phase 2 PTSD trial. The primary endpoint of the trial is change in total symptom severity score using the clinician administered PTSD scale or CAHPS V from baseline to the end of treatment.

Speaker 4

CAHPS V is a structured 30 item clinical interview. It is a validated instrument considered the standard for diagnosing in assessing patients with PTSD and is an endpoint that has been determined to be appropriate for regulatory purposes. Beyond PTSD diagnosis, it also allows physicians to evaluate the severity of symptoms and impact on social and occupational function. The trial has several secondary endpoints, including changes in scores on Clinical global impressions of severity

Speaker 5

and the

Speaker 4

patient global impression of severity scales from baseline to the end of treatment. The ongoing trial is enrolling approximately 270 patients and assessing 2 doses of JZP-one hundred and fifty compared to placebo, which we believe adequately powers the trial, assess whether JCP-one hundred and fifty is clinically meaningful in this patient population. We expect top line data by the end of this year. We are excited about the potential of JZP-one hundred and fifty and look forward to updating you on our progress. Turning to Slide 22, we are pleased to recently receive IND clearance for JZP-eight ninety eight and expect to initiate a Phase 1 trial later this year.

Speaker 4

JCP-eight ninety eight is an engineered interferon alpha Cytokine Prodrug that is activated specifically within the tumor microenvironment where it can stimulate interferon alpha receptors on cancer fighting immune effector cells. High dose interferon alpha therapy is approved in multiple tumor types, but is used sparingly Based on its toxicity profile, systemic delivery of cytokines can cause serious toxicity to peripheral tissues. This leads to poor clinical outcomes Given ineffective antitumor immune activation and unmanageable toxicity in patients, JZP-eight ninety eight is a conditionally Activated interferon alpha, which is selectively activated in the tumor microenvironment. Through this approach, biologically relevant exposures are coupled with optimal cytokine potency while limiting toxicity in other tissues. We are excited to bring this novel molecule into the clinic later this year.

Speaker 4

Overall, our R and D team continues to advance multiple programs from our neurosciences and oncology pipelines. And we're looking forward to multiple near term data readouts. Now I will turn over the call to Renee for financial update. Renee?

Speaker 6

Thanks, Rob. I'll start with our top and bottom line results on Slide 24. As a reminder, our full financial results are available in our press release and 10 Q. In the Q2 of 2023, We achieved $957,000,000 in total revenues. This was driven by growth of our key products in both neuroscience and oncology, including another quarter of double digit growth of Zywave, Epidiolex and Rylase compared to 2Q 2022.

Speaker 6

We're particularly pleased with the continued trajectory of Zywave even with competition since the beginning of the year. Coupled with the continued Epidiolex momentum and strong growth for Rylase, we saw total revenue increase 3% compared to 2Q 2020 2. Our disciplined capital allocation and focus on operational excellence drove adjusted net income of $325,000,000 growth of 6% compared to the same quarter in 2022. We continue to generate significant cash from our business, Recording approximately $617,000,000 of cash from operations in the first half of twenty twenty three, an increase of more than $100,000,000 compared to the same period in 2022. Our strong overall financial position means we have significant flexibility to invest in priority commercial and R and D programs as well as corporate development opportunities.

Speaker 6

Corporate development is a core component of Vision 2025 and we remain active in exploring opportunities to expand our commercial portfolio and pipeline. Turning to Slide 25, we are updating our total 2023 revenue guidance to a range of 3.725 to $3,875,000,000 reflecting a $25,000,000 increase at the midpoint. This update is underpinned by an increase of $20,000,000 at the midpoint of our neuroscience revenue guidance. Our increased 2023 neuroscience revenue guidance incorporates our continued confidence in the durability of our oxybate franchise, in part based on the performance and growth of Zywave during the first half of the year, a time period in which we saw of high sodium oxybate competition. With regard to high sodium authorized generics, we expect our royalties from Hikma, which is the only volume unlimited authorized generic to be significantly higher in the second half of twenty twenty three relative to the first half.

Speaker 6

During the second half of twenty twenty three, the royalty rate from Hikma to Jazz becomes fixed at a rate where we and Hikma Both have substantial economics. We also received royalties on other high sodium oxybate AEGs, all of which are restricted to a low single digit percentage of Xyrem sales volume. As Dan noted earlier, Currently, only one additional AG has been launched. Our 2023 oncology guidance remains unchanged and reflects expectations of continued double digit growth for this franchise led by Rylase with a revenue range of $950,000,000 to $1,050,000,000 and a midpoint of $1,000,000,000 Continuing to Slide 26, Our capital allocation strategy includes investment in commercial brands to drive top line growth and our pipeline to drive long term growth and in corporate development where we remain actively engaged in assessing opportunities and which remains an important pillar of our growth strategy. We are maintaining our prior non GAAP SG and A and R and D guidance for 2023.

Speaker 6

Consistent with our capital allocation strategy, Our enhanced investment in R and D is a direct result of our success in diversifying and advancing our pipeline, as well as prioritizing those programs that we believe will have the biggest impact for patients while delivering value and contributing to our growth. We believe there is tremendous unrecognized value potential in our stock and therefore supported by our strong cash flows and aligned to our strategic and disciplined approach to capital allocation, we have resumed share repurchases under our existing repurchase program. In the Q2, we completed approximately $100,000,000 of share repurchases. As of the end of the second quarter, Approximately $336,000,000 remained available for share repurchases under our current plan. Importantly, given our strong overall financial position, we are able to repurchase shares without compromising our ability to execute business development opportunities and invest in our innovative R and D program.

Speaker 6

On the bottom line, we to $1,290,000,000 to $1,340,000,000 which implies a 41% year over year ANI growth at the midpoint. I would also like to highlight, we raised our non GAAP adjusted EPS guidance to a range of $18.15 to $19 an increase of $1.20 at the midpoint, primarily driven by our increased revenue and ANI outlook as well as reductions in our fully diluted shares outstanding. The decrease to our weighted average ordinary share guidance relates to both our share repurchase and to our recent irrevocable To settle in cash, the principal of our $575,000,000 exchangeable senior notes due in 2024, thereby limiting potential dilution from these instruments. With our strategic investments, expanding product portfolio, R and D progress and focus on operational excellence, we believe we are well positioned to achieve vision 2025 and deliver further diversification, sustainable growth and enhanced value to patients and shareholders. I'd now like to turn the call back to Bruce.

Speaker 2

Thanks, Renee. I'll conclude our prepared remarks on Slide 28. The first half of twenty twenty three has been driven by focused execution and strong commercial results evidenced by the durability of our oxybate franchise, Continued growth of Epidiolex and strength in Rylase sales. We continue to advance our pipeline and invest in long term growth, And we have as many as 4 late stage data readouts through 2024 that have the potential to further diversify and transform our business. Our latest pipeline addition, sandedatumab, is approaching several near term clinical and regulatory milestones.

Speaker 2

Given its applicability across multiple tumor types and lines of therapy, we believe zenidetimab has $2,000,000,000 plus in peak sales potential. We also remain focused on strategic capital allocation. With our strong cash flow, balance sheet and margins, we have the financial flexibility to make significant investments across commercial, pipeline and corporate development to drive sustainable growth and enhanced value. That concludes our prepared remarks. I'd now like to turn the call over to the operator to open the line for Q and A.

Operator

We will now begin the Q and A session. Please pick up your handset before asking your question. We do ask that you please limit yourself to one question. We will pause here briefly as questions register. The first question comes from the line of Jason Gerberry with Bank of America.

Operator

Your line is now open.

Speaker 2

Well, Hey guys, thanks for taking my questions. Mine is on the Phase 3 ZANI GEA study that's going to read out First half next year, can you help frame what sort of data we can expect on the primary efficacy measures, the PFS, DOS? Is this a first interim? I'm just wondering if DFS and OS will be mature or the focus really is on ORR in this data cut. Thanks.

Speaker 2

Yes. Thanks, Jason. Rob, maybe I'll throw that one to you.

Speaker 4

So just to clarify, what we said previously was in 2024, we didn't specify exactly when. And in that, we are referring to PFS as the initial readout.

Operator

The next question comes from the line of Joseph Thorne with TD Cowen. Your line is now open.

Speaker 5

Hi there. Good afternoon and thank you for taking my question. Maybe one on the upcoming PTSD readout, maybe what's a clinically meaningful benefit on that CAHPS scale? And when you Talk about the type of patient enrolled. Are these on concomitant SSRI or are they SSRI Treatment failures, can you just put that in the context a little bit for us?

Speaker 5

That would be great. Thank you.

Speaker 2

Yes. Go ahead,

Speaker 4

Rob. Sure. So, we haven't said specifically what Treatment effect that we've powered to, but you could draw some of your own inferences by looking at the sample size, etcetera, that's listed on ct.gov. And you'll note that it's a placebo controlled trial with 2 dose levels,

Operator

Thank you. The next question comes from the line of Mark Goodman with Leerink Partners. Your line is now open.

Speaker 7

Yes. Hi. Could you please give us a little more Color on the comment that you made regarding the operational issues with the specialty pharmacy, in the oxybate franchise and just give us How much you think it may have impacted patients in the quarter or whatever you think it may have impacted or is it impacting anything about Q3? Thank you.

Speaker 2

Yes. Thanks for the question, Mark. Kim, you want to take that?

Speaker 8

Sure. I'd be happy to. So Let me start out by saying that we continue to be very confident in the strength and durability of our Activate franchise As low sodium biwave continues to be the activator choice and the only approved therapy for IH, the decrease in total average Active Jazz oxybate patients this quarter primarily reflects the expected impact to Xyrem as a result of Zywave adoption and the availability of AG Xyrem. In terms of Zywave and the average number of Patients on Zywave exiting the quarter, there was what we're calling an operational change at our specialty pharmacy, which Unfortunately, caused delays in some, Zywave patients getting their refills on time. So this has been addressed.

Speaker 8

And importantly, I think to understand is that the overall 2Q XYwave HCP inpatient The overall market demand for Zywave was in line with our expectations and with what we saw in prior quarters. So this really was an issue at the pharmacy that affected patients, some patients getting refills, not with the overall demand for The benefits of reducing sodium intake in the market continue to resonate with our customers and we're very confident in the growth opportunity for Zywave and the durability of the franchise. And while we expect Xyrem to continue to decline in line with the Zywave and AG adoption. As you heard, we've raised our full year 2023 financial guidance and increased our neuroscience revenue guidance at the midpoint. So overall, our increased neuroscience revenue guidance accounts for the performance in growth of Zywave during the first half of the year, in a time period in which we saw the introduction of high sodium Occupate competition.

Speaker 8

So our focus remains on continuing to grow the low sodium zywave, which is already as you saw annualizing At well over $1,000,000,000 and we remain very confident in the durability of the business.

Operator

Thank you. The next question comes from the line of Akash Tewari with Jefferies. Your line is now open.

Speaker 9

Hey, thanks so much. So can you walk me through your confidence on the 2,000,000,000 sodium oxybate number for your long term guidance? Let's say you continue to add about 250 IH patients a quarter until 2025, that kind of implies IH will contribute about $600,000,000 in sales by 2025. That means that your narcolepsy franchise, which is about $1,700,000,000 today, only declined to about $1,400,000,000 for you to hit that $2,000,000,000 watermark. How you achieve that with generic and Avadel launching?

Speaker 9

Like what are we missing here? Also, I think you've previously mentioned the majority of the erosion impact The sodium oxybate franchise will occur in 2023. Is that still the case today given your revised NEROU guide? Thanks so much.

Speaker 2

Yes, Akash, thanks for the question. We outlined our confidence that OXIBATE Our business at Jazz would contribute about $2,000,000,000 toward Vision 2025 at the beginning of last year, at the beginning of 2022. Obviously, we reiterated that coming into 2023 and we've now actually increased our short term guidance in 2023. As a reminder, What we meant by that $2,000,000,000 was the combined revenues from Zywave, both in narcolepsy and in idiopathic hypersomnia, Continued brand Xyrem sales and our royalties on any AGs that come to market through our system. And we continue to feel confident in that.

Speaker 2

You didn't specifically mention the royalties in your analysis. I'll remind you that the contribution from those royalties is expected to be significantly higher in the second half of 2023 relative to the first half and that the royalty structure we've disclosed from the Hikma Our relationship will actually reset up again in 2024. So it's the combination of all those things That get us to the durability. Our big focus, as Kim explained, is on growing Zywave. This is the longer healthier choice for patients given the benefits of low sodium in this chronic treatment And we'd like to see more and more patients get the benefit of Zywave moving forward.

Operator

Thank you. The next question comes from the line of David Amsellem with Piper Sandler. Your line is now open.

Speaker 10

Hey, thanks. So I wanted to come back to The Vision 20, 25 targets, particularly the $5,000,000,000 top line. It seems like The Street in the broader investor community is not quite there regarding the $5,000,000,000 target. So Just can you articulate what you think we're all missing? Is it Something surrounding Epidiolex, is it Zanadatinib for instance is GEA biliary tract cancer or both in that 2025 number, just help us understand why there seems to be daylight between that target and what folks are modeling for 2025?

Speaker 10

Thanks.

Speaker 2

Yes. Well, let's review where we are toward Vision 2025. Again, we rolled this out at the beginning of 2022. We're 6 quarters into a 4 year period, we're feeling very good about the performance of our business overall, Both relative to our guidance for 2023, which has now been raised on both the top and the bottom line and our Vision 2025. I just spoke about oxybate and the durability of that franchise and the positive progress we're seeing with Zywave.

Speaker 2

But let me remind you that half of our business today is already coming from Epidiolex and oncology. We're seeing double digit growth in our 3 lead assets, Cywave, Epidiolex and Rylase, which together are accounting for about 66% of our revenues. And when you look at the oxybate piece, Xyrem is now less than half of that piece of our business. So we've got growth coming in all of our key franchises, which we estimated would Contribute in 2025 approximately $4,500,000,000 in aggregate. We left a placeholder in Vision 2025 intentionally for our ongoing corporate development activities and said that products that were not part of our portfolio when we started Vision 2025 could contribute That last $500,000,000 Zanidatumab may well contribute to that.

Speaker 2

We're not saying it's going to contribute all of the $500,000,000 to be clear, But that was something added to the portfolio after we began this process. And we remain very interested in continuing to access new commercial products and pipeline products through our corporate development efforts moving forward. Our financial position is strong. If you look at our cash and investments, about $1,400,000,000 If you look at our cash flow in the first half of the year approaching $620,000,000 Our leverage is down. So we feel like we're well positioned to continue to bring in new assets.

Speaker 2

As we have over the company's history, if you go back any 2 to 3 year period in our history, you'll generally see us do a significant transaction. And we thought it was unfair to assume that we would suddenly stop doing transactions, particularly given our Successful launches of a number of products in a row here and our strong financial position.

Operator

Thank you. The next question comes from the line of Ami Fadia with Needham. Your line is now open.

Speaker 11

Hi, good evening. Thanks for taking my question. Perhaps continuing on the vein of The placeholder for corporate development, can you talk about your level of confidence in being able to hit a majority of that Where are you caught that currently in terms of alternative options in terms of use of capital? Would you consider buying back more shares? Should you not be in a position to execute on such a deal?

Speaker 11

Thank you.

Speaker 2

Yes. Thanks, Ami. Renee, can you jump in on this one?

Speaker 6

Sure. I'm happy to. So, Ami, we've talked quite a bit about our strategic and disciplined approach to capital allocation and our priority 1st and foremost is investing in growth. So we're investing behind our commercial launches and growth Programs were investing behind the pipeline and we expect to continue to invest in corporate development as Bruce mentioned previously. It has been an important pillar of growth for us and we expect that to continue to be the case.

Speaker 6

In addition, we also look at Opportunities in terms of managing the balance sheet strategically. Bruce also mentioned we delevered pretty quickly. So we're in a great position today to be opportunistic in terms of additional investments for the balance sheet. And we did take the opportunity just given what we view quarter and we think that was the right thing to do. In terms of future repurchases, we'll continue Specific to the $500,000,000 placeholder, as you've heard on the call today, we're really excited about the opportunity for Zanidetimab.

Speaker 6

We think that's That to cover a large majority of the $500,000,000 but it's certainly we certainly expect that to contribute. And then beyond that, we're quite active from a corporate development perspective. As you heard me say previously, we're not going to overpay Just to be able to meet this growth objective, we also don't think that we'll need to. We do think there are opportunities Out there both within neuroscience and oncology, but also within the rare and orphan segment more broadly. As you know, the vast majority of our commercial products currently do fall within that category and we think there are applicable learnings In terms of working directly with patient groups and serving the needs of patients, our underlying infrastructure Those learnings can be shared both from our existing experience to other rare and orphan conditions.

Speaker 6

So today, we feel quite confident in our ability to transact. We're well capitalized to be able to do so, as Bruce mentioned previously. And we think we've established a great track record as a partner of choice to be able to do so as well.

Operator

Thank you. Our next question comes from the line of Gregory Renza with RBC Capital Markets. Your line is now open.

Speaker 5

Great. Good afternoon, Bruce and team. Congrats on the quarter. Thanks for taking my question. Bruce, maybe just a little bit on Epidiolex and just with respect to Dan's comments on the drivers for potential continued growth.

Speaker 5

Just curious if you can comment a bit on any particular areas or drivers that kind of outsized and help to propel the growth that you're expecting, Certainly, last quarter, Q1, a little seasonality and seeing the momentum that you're speaking about now. I'm just curious how you see that playing out in the near term. Thank you very much.

Speaker 2

Yes, Greg, thanks for the question. Dan, you want to take Epidiolex?

Speaker 3

Yes. Thanks, Bruce. So with Epidiolex, it's another quarter of double digit growth with 15%, Greg. So really pleased to see Yes, the continued initiatives that we outlined on the call, continued face to face interactions, very important in the treatment centers, getting to We've been enhancing our focus on the adult setting. In particular, in the U.

Speaker 3

S, we've gone after long term care And seeing increasing penetration there. We've also been educating HCPs About the benefits of Epidox beyond seizure control and that was highlighted in the become data, Which was presented at the end of last year, which talks about cognitive and behavioral benefits. And We look forward to continuing to lean into that area, both with caregiver surveys and even interventional studies. And so we've got a real commitment to Continuing to generate data, but within the indications and kind of outside those indications, outside the U. S, the launches continue to go well.

Speaker 3

We're at The 23 countries globally, we've had 6 positive pricing reimbursement decisions to date In the U. S. Sorry, outside the U. S. And importantly, we've got a Phase 3 study in what we think could be Very significant market for us with Epidiolex in Japan.

Speaker 3

And so that's enrolling nicely and we look forward to providing updates in the coming quarters.

Operator

Thank you. The next question comes from the line of Annabel Samimy with Stifel. Your line is now open.

Speaker 12

Hi. Just a couple more on Epidiolex. So you mentioned a couple of times now expanded indications. The only indication we know of that you're working on is So, are there others that we don't know about that you plan on expanding into? And also with the EU launch, we now have 23 countries approved, I guess, 5 in the major EU countries, but are all those countries on board?

Speaker 12

Should we now see a significant expansion in Epidiolex ex U. S. Thanks.

Speaker 2

Rob, would you like to talk a little bit about some of the additional data we're Generating with Epidiolex and then maybe Kim, you could talk a little bit about the potential for broader use of the product over time.

Speaker 4

Yes. So, you're right that we're evaluating EMAS and the objective there is to generate data And yet another seizure type adding to the 3 indications we have, really trying to demonstrate that Epidiolex is Broadly active across different seizure types, regardless of the underlying etiology. We also continue to provide evidence around the indications we have, both in terms of anti seizure effectiveness, But also in terms of other potential benefits of Epidiolex. And you heard Dan refer to the caretaker survey And we continue to support and do studies along those lines as well.

Speaker 8

Yes, sure, Rob. So I'll say that we've had very nice growth in the 3 indicated populations as well as Growth over time in the base of prescribers that are utilizing Epidiolex. And what we see traditionally as Our customers get more and more experience with the product, usually starting in the three indications. They see what it can do for their patients in terms of seizure control and now beyond Seizure control that frankly they've been hearing about from caregivers since day 1 of the launch. And this really gives them the confidence to start using it more broadly across the spectrum of various seizure types and so forth.

Speaker 8

So we're clearly not And promoting it outside that, but this is what we hear from the providers once they get the experience, they see the efficacy, they do start to utilize it earlier And more broadly, across their patient population. And really the data, as we've talked about, that we've been Sharing to really increase the efficacy perception of the product, the Clobazam combination data in and of itself Get them to stop and think about why am I reserving this for certain patient types. Most of my patients are on clobazam. Most of them could still benefit from additional seizure control or beyond seizure benefits, and it really gets them to start thinking about I should be using this more and more and more of these patients that are taking clobazam.

Operator

Thank you. Our next question comes from the line of Jeff Hung with Morgan Stanley. Your line is now open.

Speaker 5

Thanks for taking my question. For Rylase, you've talked about focusing on adolescents and young adults. Can you talk a little bit more about how that's going and how much That opportunity remains speed draw.

Speaker 4

Yes, Kim?

Speaker 8

Sure. Love to. Love talking about Rylase. What we've really seen with Rylase is just lots of in general. And I think as we told you early on, it didn't take very long for healthcare providers to have confidence in the supply and to return Best clinical practice in terms of switching patients at the first signs of hypersensitivity at this point in the pediatric market, It's been added almost universally to the protocols in that setting.

Speaker 8

So at the beginning of this year, we did tell you that we were looking to start trying to expand the adolescent and young adult market. There was quite a bit of usage, a fair amount of usage of the product In adolescence and young adults that were being treated in the pediatric center per pediatric protocol, but the adult centers We're less educated, familiar and experienced with using Rylase in this setting. And so we've gone out there this year. We have now spent 2 quarters educating them on the product about the importance of switching As quickly as possible when they see a hypersensitivity reaction and we see nice orders coming through and a nice growth rate happening in this setting. So We don't think we're done.

Speaker 8

We haven't gotten all of these centers to start using it. Some of them are still dabbling. So there definitely is Some more growth to be had there. And I think it's important to remember that in the adult setting, because this is a weight based Product, the average dose is higher than in the pediatric center. So each adult patient is worth more.

Speaker 8

We're really pleased with Rylase at this

Operator

stage, but we think there's

Speaker 1

a little bit more room to grow here

Speaker 8

in the U. S. And then of course ex U. S.

Operator

Thank you. Our next question comes from the line of Balaji Prasad with Barclays. Your line is now open.

Speaker 13

Good afternoon. This is Shao on for Balaji. Thanks for taking our question. Just a quick one on your OX2R program. On the data for TAK-nine ninety four that was recently published on New England Journal of Medicine and the factor for liver for TAK-nine ninety four was the impact of reactive metabolics.

Speaker 13

So Takeda also mentioned that TAK-eight sixty one And TAK-nine ninety four do have the overlapping metabolic pathways. So do you think JZP-four forty one is well differentiated with

Speaker 4

Rob? Yes. Thank you for the question. So, the liver toxicity associated with 994 was known at the time that we entered into the partnership with Sumitomo. And we focused on chemical series that we thought were distinct enough Such that, that wouldn't that risk of liver toxicity wouldn't be carried over.

Speaker 4

And so we do think that our molecule is

Operator

Thank you. The next question comes from the line of Mohit Fonsal with Wells Fargo. Your line is now open.

Speaker 14

Great. Thank you for taking my question Congrats on all the progress. So maybe like one question regarding the authorized generics of Sirem. Do you think they will have any impact on IH market as well? Because in our talks with doctors, they think that they can Prescribe it as long as payers cover it payers would probably cover it.

Speaker 14

So do you see this as a threat Because doctors could use it off label. Thank you.

Speaker 2

Yes. Well, I'll remind you that Xyrem did not do a comprehensive clinical program in the way that Zywave has In IH, there's slightly different dosing information in the label. And while you're right, the physicians can prescribe the product that does not always mean that that product will be successfully reimbursed. Kim, any comments you want to make on the marketplace?

Speaker 8

Yes, sure. So yes, we've seen traditionally the payer at that HCPs have had trouble getting Coverage for OxoBate for idiopathic hypersomnia because payers restricted it with the introduction of ZyWay for idiopathic Hypersomnia, we have achieved nice coverage as we do with narcolepsy of 90% of commercial lives. Having coverage, And there usually is utilization management criteria in place there and certainly heavier utilization management criteria around non indicated products. So we feel confident that while a small portion of healthcare plans May cover high sodium oxybate, in particular, the AG for idiopathic hypersomnia. Most of them are following the FDA approved label, and XYwave is the only FDA approved treatment for idiopathic hypersomnia.

Speaker 2

And Rob, Maybe you could just expand a little bit on that slightly different dosing information.

Speaker 4

Yes. Bruce, just specifically with regard to narcolepsy or IH or?

Speaker 2

I meant IH, but you can talk about dosing Flexibility generally.

Speaker 4

Sure. So starting with IH then, the clinical trial allowed for an initial dose of up to 6 grams. And at the time, it was designed that way because there was some uncertainty around whether IH patients would wake up Not to take that second dose. What we found in the clinical trials that with initiation of Zywave, Patients with IH improved substantially, and in fact, we're able to go ahead and take the second dose. And overall, that was the more common dosing regimen even though in the trial and we find that to be the case in clinical practice as well.

Speaker 4

Along those lines for narcolepsy, as you know, Zywave also has dosing flexibility Allow for uneven doses and we find that patients really do prefer this. Oftentimes Schedules are different from one patient to another, but even within a patient, schedules may differ And they like the flexibility of uneven doses potentially.

Operator

Thank you. The next question comes from the line of Joon Lee with Truist Securities. Your line is now open.

Speaker 9

Hi, congrats on the quarter and thanks for taking our questions. How do you quantify the trade off between having a once a night drug with high sodium versus twice a night drug with no sodium? Isn't having to wake

Speaker 14

up in the middle of

Speaker 9

the night also unhealthy? And as a quick follow-up, do you have any views on reboxetine currently in Phase 3

Speaker 2

Yes. Rob, maybe I could have you jump in a little bit on the nighttime impact of oxybate therapy.

Speaker 4

Yes. Happy to, Bruce. So we know that narcolepsy patients have significantly disrupted nighttime sleep. We also know that oxybates have a very big impact in improving the architecture of nighttime sleep. And we think that's why for a short acting drug, patients then have substantial improvement in daytime symptoms like cataplexy Excessive daytime sleepiness.

Speaker 4

When you look across studies of oxivates, whether that be a fixed dose high sodium version Or immediate release, oxybate, There is improvement. It's very comparable. There's no evidence that a fixed dose regimen improves the supine and nighttime sleep to a greater extent. Patients typically do not normalize their sleep, And there's really no evidence that waiting to take a second administration impacts one way or another.

Speaker 2

And then Rob, I think there was a question on reboxetine at the end of the question as well. And,

Speaker 4

sorry, Bruce, could you just repeat that for me then?

Speaker 2

I think the question was, any thoughts on data on reboxetine?

Speaker 4

I mean, I'll just jump in and say,

Speaker 2

historically, we in our conversations with KOLs, we've not Found that there is as much interest in that as other drugs available or in development. This has been available in certain markets for a long time in treatment of other diseases, But we haven't heard of a huge success in this patient population in the U. S.

Speaker 4

Sure. Okay. Thanks for clarifying that, Bruce. And I would just say that, our focus with Zywave is the nighttime administration to address the underlying cause of disrupted nighttime sleep, which has profound effects in daytime symptoms. Revoxetine is one of several drugs that's used as a daytime alerting agent And it's sometimes complementary to oxybate, but we don't think a substitute for many patients.

Operator

Thank you. The next question comes from the line of Charles Duncan with Cantor Fitzgerald, your line is now open.

Speaker 15

Hey, Good evening, Bruce and team. Congrats on good commercial performance in the quarter and thanks for taking our questions. Sorry to ask about a nuance in the pipeline, but it actually relates to the next readout that Could come and that's on JZP-one hundred and fifty and PTSD, tough disorder. I guess I'm wondering if Given that this is an early Phase 2, would you focus more on stat sig and effect size Or the overall results of the study to enable the drug to move forward. And then In terms of the statistical analysis plan, it looks like a wide range of doses.

Speaker 15

So I guess I'm wondering, Is it each dose relative to placebo or would you combine doses the analysis of the 2 Those groups versus placebo. Thanks.

Speaker 2

Rob, you want to take the 1 50 question?

Speaker 4

Yes. Thanks, Bruce. We do think the CAHPS V is a comprehensive composite endpoint. It has Regulatory endorsement as an endpoint that could be used for approval and it does capture quite a bit The broad range of symptomatology in the PTSD patients. So we do think that that's a good way to measure the effect of the drug.

Speaker 4

We are measuring other things in exploratory ways as well, which we certainly will take into account. You're right that the trial is 3 arms. There's 2 active dose levels in placebo. And given the sample size that we have, we feel we're well powered to make comparisons with both of those different dose levels against placebo. We don't have to collapse across those arms.

Speaker 2

Well, I think that was our last question. So I just want to jump in and thank All of our questioners for moving us through, I think, most of our commercial business, a lot of our pipeline, and our strategy. Hopefully, people feel great about the quarter on the top line, on the bottom line, the new guidance, increased diversification and the momentum we have in our business, Particularly our 3 key growth drivers in Zywave, Epidiolex and Rylase. I'd just like to close today's call by recognizing All of our Jazz colleagues for their efforts in delivering new therapeutic options to patients and thank our partners and shareholders for their continued confidence and support. Thank you all for joining us today.

Operator

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

Remove Ads
Powered by Quartr
Earnings Conference Call
Jazz Pharmaceuticals Q2 2023
00:00 / 00:00
Remove Ads