Q3 2019 Earnings Call

Following an introduction some of the company will open the call into question.

Chris: Following an introduction from the company, we will open the call to questions. I will now turn the call over to Kathy Luttrell, Head of Investor Relations at Jazz Pharmaceuticals. Thank you, Chris.

Well now turn the call over to Kb, Kathy Littrell head of Investor relations it drags from mature.

Thank you, Chris and thanks to those of you joining our investor call today, We reported our third quarter 2019 financial results and updated our financial guidance for 2019 to press release and the slide presentation accompanying this call are available in the Investor section of our website.

Kathy Luttrell: And thanks to those of you who joined our investor call today. Today, we reported our third quarter 2019 financial results and updated our financial guidance for 2019. The press release and the slide presentation accompanying this call are available in the investor section of our website. On the call today are Bruce Cozadd, CEO; Sam Swisher, President; and Robert Iannone, Executive Vice President, R&D. Joining for the Q&A session are Mike Miller, Executive Vice President, U.S. Commercial; Alan Lang, Senior Vice President, Clinical Development, and Acting CMO. And I'd also like to remind you that some of the statements we will make on this call relate to future events and performance, rather than historical facts and our forward. Examples of forward-looking statements include those related to our future financial and operating results, including 2019 Financial Guidance and Goals.

On the call today Arboretum code that CEO , Dan Swisher President.

Executive Vice President R&D, joining for the <unk> session or Mike Miller Executive Vice President U.S. commercial Alan nine.

Yeah, I'm, sorry, I senior Vice President clinical development enacting CMO.

And I'd also like to remind you that some of the statements. We will make on this call relate to future events and performance rather than historical facts and our forward looking examples of forward looking statements include those related to our future financial and operating result, including 2019 financial guidance angle future growth and growth strategies.

Kathy Luttrell: For growth and growth strategy, product launches, sales, and volume; regulatory activities, ongoing and future clinical trials, and other product development activities. Offered Development. These forward-looking statements involve risks and uncertainties that could cause actual events, performance, and results to differ. They are identified and described in today's press release, Company and Slide Presentation, and Under Risk Factors in our Form 10-Q for the quarter ended June 30, 2019, which we will file shortly. We undertake no duty or obligation to update our forward-looking statement.

Product launches sales in volumes.

Supply challenges regulatory activities ongoing of future clinical trials and other products development activities in corporate development effort. These forward looking statements involve risks and uncertainties that could cause actual events performance and results to differ materially.

They are identified in described in today's press release, any accompanying slide presentation and under risk factors in our Form 10-Q for the quarter ended June Thirtyth 2019, and our Form 10-Q for the quarter ended September Thirtyth 29 team, which we will file shortly we undertake no duty or obligation to update or forward looking.

Uh huh.

Kathy Luttrell: On this call, we discuss non-GAAP financial measures. We believe these measures are helpful in understanding our past financial performance and our potential future results. However, they are not meant to be considered in isolation or as a substitute for comparable reported GAAP measures.

On this call we discuss non-GAAP financial measures. We believe these measures are helpful and understanding our past financial performance and our potential future results, they're not meant to be considered in isolation or as a substitute for comparable reported GAAP measures reconciliations of GAAP to non-GAAP financial measures discussed.

Bruce C. Cozadd: Reconciliations of GAAP to non-GAAP financial measures discussed on this call are included in today's press conference and slide presentation available on our website. I'll now turn the call over to you. Good afternoon, everyone. Thank you for joining us. We delivered strong top and bottom line growth in the third quarter while executing on commercial, R&D, and corporate development goals. I'll start by sharing some key recent highlights.

This call are included in todays press release and slide presentation available on our website I'll now turn the call over to Brian .

Good afternoon, everyone. Thank you for joining us.

We delivered strong top and bottomline growth from a third quarter, well executing on commercial R&D and corporate development goals Oscar by sharing some key recent highlights.

Bruce C. Cozadd: We presented positive Phase 3 data at the World Sleep Congress on JCP258, our novel Oxabay product candidate with 92% less sodium than xyrum, and made progress in preparing our NDA submission. We plan to redeem our priority review voucher for the JCP 258 NDA for the treatment of EDS and cataplexy and narcolepsy and expect to submit it in January 2020. Based on expected FDA review timelines, we could see potential approval as early as the third quarter next year. We launched Sanosi in the U.S. in July and are observing growing prescriber interest in product trials, increasing prescriptions, and improving patient outcomes. We are engaged in SENOSA EU pre-launch activities as we anticipate a positive CHMP opinion this month and an EMA decision in early 2020. We worked with FDA and the Children's Oncology Group to finalize the protocol for the pivotal study of JZP458, our recombinant erythromycin.

We presented positive phase three data set the world Sleep Congress on GBP 258, or novel Oxybate product candidate, but 92% less sodium wins lightly and made progress and preparing R&D a submission.

We plan to redeem our priority review voucher for the JCB to 58, India for the treatment of Bts and cataplexy narcolepsy and expect to submit in January 2020.

Based on expected after the a review timelines, we could see potential approval as early as third quarter next year.

We launched a no see in the U.S. in July and are observing growing prescriber interest in product trial, increasing prescriptions and improving patient access we are engaged in San Jose you pre launch activities as we anticipate a positive C.H.M.P. opinion this month and he made decision in early 22.

Morning.

We worked with hefty a on the children's oncology group to finalize the protocol for the pivotal study of JCP for 58, our recombinant for Wynia asparaginase.

Bruce C. Cozadd: We are working toward recruiting the first patient this quarter and target study completion next year. Recently, FDA granted fast-track designation for JCP 458 for the treatment of acute lymphoblastic leukemia. We enrolled the first patients in multiple vixios and epithelial clinical studies. And we also continue to strengthen our development pipeline with the acquisition of Cavion and worldwide rights to CX 8998. Pencil Treatment of a Sensual Tremor Now, I'll provide an update on our Key Sleep Neuroscience Program. We're in the early stages of our U.S. CENOSI launch and are looking forward to bringing CENOSI to patients outside the U.S. where there is currently no licensed drug treatment option for EDS and OSA and limited treatment options for EDS and narcolepsy. We are pleased with the positive feedback we've received from patients, health care providers, and key opinion leaders in the U.S. and are encouraged by upward During the third quarter, there were more than 1,000 unique prescribers of Tenosi, resulting in more than 3,300 scripts.

We are working toward recruiting first patient this quarter and target study completion next year recently FDA granted fast track designation for JCP for 58 for the treatment of acute lymphoblastic leukemia.

We enrolled the first patients and multiple Vyxeos and Defitelio clinical studies and we also continued to strengthen our development pipeline with the acquisition of Caviar and worldwide rights to CX 89, 98 for the potential treatment the central true.

Now I'll provide an update on our key sleep neuroscience programs.

We're in the early stages of our U.S. and no CE launch and are looking forward to bring sonos you to patients outside the U.S., where there is currently no license drug treatment option for yes, and I was saying and limited treatment options for pediatric narcolepsy.

We're pleased with a positive feedback we've received from patients health care providers and key opinion leaders in the U.S. and are encouraged by upward trending demand and rising refill rates, which won't really indicate positive patient experience and growing awareness of snow season for the treatment of Bts and narcolepsy and I will say.

During the third quarter, there were more than 1000 unique prescribers of snow see resulting in more than 3300 scripts.

Mike Miller: Samples and vouchers are a key resource for health care providers, and we will continue to utilize these programs so physicians can gain clinical experience by helping their patients try Sinovac. Additionally, we're expanding outreach beyond existing Xyron prescribers to educate and establish relationships with new prescribers, including those who primarily manage OSA patients. During the third quarter, we completed more than 100 speaker programs providing peer-to-peer education about the pathophysiology of EDS and the role of pharmacotherapy in treating EDS and narcolepsy in OSA. Our Non-Branded Consumer Campaign continues to raise awareness, and we are seeing strong engagement as evidenced by growth in unique visits to a different kind of tire.com and Sanosi.com, to help We launched comprehensive patient access programs to help lower patient out-of-pocket costs. Approximately 90% of scripts that have been adjudicated through these programs have resulted in a patient copay of $9.

Samples and vouchers are a key resource for health care providers, and we will continue to utilize these programs. So physicians can gain clinical experience by helping their patients tries to Tennessee.

We're expanding our reach beyond the existing xyrem prescribers to educate and establish relationships with new prescribers, including those who primarily manage over say patients.

During the third quarter, we completed more than 100 speaker programs, providing peer to peer education about the pathophysiology of videos and the role of pharmacotherapy and treating Jaeson narcolepsy, you know I say.

Our non branded consumer campaigns continue to raise awareness and we're seeing strong engagement as evidenced by growth in unique visits to a different kind of tired dot com answer no Si dot com.

To help improve appropriate patients can experience was you know, saying, we launched comprehensive patient access programs to help lower patients out of pocket costs, approximately 90% of scripts that had been adjudicated through these programs have resulted in a patient co pay of $9.

Bruce C. Cozadd: Now I'll spend a moment discussing our strategy to optimize commercial coverage and patient access for our current and future sleep products. We're pleased that early in the launch, Sanosi has been added to the Express Scripts National Preferred Commercial Formula. Express Scripts is one of the largest pharmacy benefit managers in the U.S., and its preferred Tier 2 status for Cynosis includes a prior authorization requirement, including step therapy of one generic weight-promoting agent, consistent with our pre-launch expectations. We are pleased with our commercial payer coverage to date and are actively engaged in contracting discussions with other key payers. Now on to Xyron.

Now I'll spend a moment discussing our strategize strategy to optimize commercial coverage and patient access for our current and future sleep products.

We're pleased that early in the launch Sonos. He has been out into the express scripts national preferred commercial formulary.

Express scripts is one of the largest pharmacy benefit managers in the U.S.

The preferred tier two status for Sanofi includes a prior authorization requirement, including step therapy of one generic week promoting agent consistent with our pre launch activities expectations.

We're pleased with our commercial payer coverage today and are actively engaged in contracting discussions with other key payers.

Now onto Xyrem.

Bruce C. Cozadd: Zyram had an exceptional quarter with bottle volume growth of 6.5% compared to the same period in 2018. We are particularly pleased that our expanded sales force was able to continue the strong growth of Xyrem while launching Cynosis. The average number of active Xyrem patients increased to 14,800, up 5% compared to the same period last year, as the only FDA-approved treatment for both cataplexy and EDS in children and adults with narcolepsy. Our efforts are focused on ensuring healthcare professionals are educated on how Xyrem may help narcolepsy patients, EDS, and cataplexy. During the third quarter, we began executing agreements for Xyron as part of our strategy to ensure ongoing patient access to our products in the current and evolving payer environment.

Xyrem had an exceptional quarter bottle volume growth of 6.5% compared to the same agreed in 2018.

We're particularly pleased but our expanded sales force was able to continue the strong growth of Xyrem wall launching so no sing the average number of active xyrem patients increased to 14800.

Five per cent compared to the same period last year.

As the only available F.D.A. if approved treatment for both cataplexy any D. S in children and adults with narcolepsy. Our efforts are focused on ensuring health care professionals are educated on how the Xyrem may help narcolepsy patients Mds and account flexi symptoms.

During the third quarter, we began executing agreements for xyrem as part of our strategy to ensure ongoing patient access to our products in the current and evolving payer environment. This will have some impact desire gross to nets. However, we believe there continued growth opportunities for Xyrem, both volume and revenue grew.

Bruce C. Cozadd: This will have some impact as Xyrem grows to net profits. However, we believe there are continued growth opportunities for Xyrem, both volume and revenue growth, as disease education efforts increase awareness and diagnosis of narcolepsy in this undertreated and underdiagnosed patient population. Before I turn the call over to Dan, I want to provide a few management announcements... We announce today that Mike Miller, our EVP U.S. Commercial, who many of you know and is on the call today, will be retiring from his role at Jazz next March after 40 years, actually more than 40 years, in the industry. Mike has built a strong team and has provided significant contributions to Jazz over the past six years.

As disease education efforts are increasing awareness and diagnosis of narcolepsy in this undertreated and under diagnosed patient population.

Before I turn the call or what is Dan I want to provide a few management updates we announced today that Mike Miller, our SVP U.S. commercial.

Who many of you know and is on the call today will be retiring from his role. China's next March after 40 years actually more than 40 years, Mike in the industry.

Mike has built a strong team and has provided significant contributions to judge over the past six years, we are beginning a search for Mike successor soon to ensure a smooth transition.

Dan: We are beginning a search for Mike's successor soon to ensure a smooth transition, after which, we'll wish Mike all the best in his retirement. Additionally, we are pleased to announce a new member of the executive management team, Sinbar Larkin, who joined Jazz in 2013 and was recently promoted to SVP, Head of Tech Ops. Along with sourcing great talent from outside of Jazz, we are always pleased when we can develop and advance leadership from within the company. I'll now turn the call over to Dan to update you on key HEMONC operational activities, then Rob will provide an update on our development programs, and I'll wrap up with an update on our financial performance. Thanks, Bruce.

After which we'll wish Mike all the best in his retirement.

Additionally, we were pleased to announce a new member of the executive management team Cinnabar Larkin, who joined jobs in 2013 and was recently promoted to SPP head of Tech ops, along with sourcing great talent from outside of jobs. We're always pleased when we can develop an advance leadership from within the company.

I'll now turn the call over to Dan. So I'll update you on key Haemobank operational activities, then Rob will provide an update on or development programs and I'll wrap up with an update on our financial performance.

Thanks, Bruce so now onto other human therapeutic area.

Dan: So now on to the HEMON therapeutic area. Starting with Vixios, in the third quarter, worldwide sales benefited. Our European team began promotional efforts in Italy in mid-September, and they secured final pricing and reimbursement in Germany. In the U.S., we continue our education and outreach initiatives, emphasizing the strong efficacy profile of... During the quarter, Guidelines for AML were updated to remove 7 plus 3 chemotherapy as a treatment option for patients age 60 and over. Fifth, secondary AML, leaving Vixious as the only recommended treatment for this patient population.

Thanks, Yes in the third quarter worldwide sales benefited from continued strong performance and you.

Our European team began.

In Italy in mid September and they secured filed pricing and reimbursement in Germany.

In the U.S., we continue our education and outreach initiatives emphasizing the strong efficacy profile in VIX, yes.

During the quarter the NCCN guidelines for and now were updated to remove seven plus three chemotherapy as a treatment option for patients age 60 and over with fifth secondary and now.

Leaving vyxeos as the only recommended treatment for this patient population.

Dan: Also, we expanded our Vixios dedicated U.S. sales team by 15 representatives during the third quarter, and they have begun promotional efforts as of October 1st. This team of 44 sales representatives will focus on physicians in key academic centers and also increase outreach to community oncologists who are more frequently making treatment decisions for AML patients. As outpatient treatment options have expanded, global performance for Daffodilia was solid in the third quarter, driven primarily by increased demand in the U.S. The EU growth was impacted by some country-specific headwinds, including typical hospital budget constraints.

Also we expanded our vyxeos dedicated sales team by 15 representatives during the third quarter and they have begun promotional efforts as of October onest.

This team of 44 sales representatives will focus on positions in key academic centers and also increase outreach to community oncologists.

More frequently making treatment decisions for AML patients as outpatient treatment options have expanded.

Global performance for Defitelio was solid in the third quarter, driven primarily by increased demand in the U.S.

And the growth was impacted by some country specific headwinds, including typical hospitals budget constraints.

Dan: Changes in Treatment Practices for Hematopoietic Stem Cell Transplants and Reimbursement for Prophylaxis. With the recent approval and launch of Desotelio in Japan by Nippon Shinyaku, Cefatilio is now commercially available in 36... Our dedicated global expansion team continues to assess New Geographic Regions to Pursue Future Marketing Authorities or Erwin H. We continue to experience lengthy out-of-stock periods in the third quarter due to ongoing supply and manufacturing issues at our sole manufacturer, PBL. We expect continued supply disruptions and manufacturing issues in the fourth quarter and in 2020. We do remain committed to working with PVL, and we're taking steps within our control to ensure Supply and the Availability of Irwin H2O. So before I turn the call over to Rob, I would like to highlight how excited we are to have Rob leading our R&D organization. His previous experience is extensive, both as a pediatric chemo physician at Johns Hopkins and Children's Hospital of Philadelphia, as well as his broad industry experience in areas such as immuno-oncology.

Changes and treatment practices for you matter politics stem cell transplants and reimbursement for prophylactic use.

With the recent approval and launch of Defitelio in Japan.

Function Jaco, except until you is now commercially available in 36 countries are dedicated global expansion team continues to assess new geographic regions to pursue future marketing authorizations.

For Irwin Nice we continued to experience lengthy out of stock periods in the third quarter due to ongoing supply and manufacturing issues at our sole manufacturer PDL.

We expect continued supply disruptions in manufacturing issues in the fourth quarter and in 2020.

We do remain committed to working with PDL and we're taking steps within our control to improve the reliability of supply and the availability of originated to patients.

Before I turn the call over to Rob I would like to highlight how excited we are to have Rob leading our R&D organization.

His previous experiences extensive.

The pediatric chemo physician.

The Johns Hopkins and children's hospital of Philadelphia.

As well as his broad industry experience in areas such as immuno oncology.

Rob: Oncology Clinical Development, ADCs, and Neuroscience at Merck, AstraZeneca, and Immunomedica. His background is invaluable as we expand and grow our R&D pipeline into new areas, such as from sleep into neuroscience, including movement disorders, and beyond our HEMONC focus into precision oncology. So I'd now like to turn the call over to Rob for an update on our development program. Thank you, Dan.

On College, you clinical development Bdcs in nerve science at Merck, Astra Zeneca and immunomedics.

His background is invaluable as we expand and grow our R&D pipeline into new areas.

Such as from sleep and to neuroscience, including movement disorders, and beyond our Hmong focus into precision oncology, including solid tumor applications.

Now, let's turn the call over to Rob for an update on our development programs.

Thank you Dan.

Rob: We continue to successfully advance multiple R&D programs during the third quarter and had a substantial presence at the World Sleep Conference in September with 15 posters and four oral presentations across our sleep portfolio. As an R&D organization, we are focused on becoming a global leader and partner of choice with the goal of bringing novel, differentiated therapies to patients through focused discovery and development and expanding the value of our commercial portfolio. Our ability to bring in innovative technologies coupled with our drug development expertise and executional excellence is critical to building and advancing a high-value and sustainable pipeline. I'll begin with development activities in our Sleep Neuroscience Therapeutic Area, starting with JCP 258. We've been working since 2012 to develop a novel Oxybate formulation that would reduce the sodium load patients get with Xyrem while still delivering the efficacy that has made Xyrem such an important option for narcolepsy patients.

We continue to successfully advanced Smokeable R&D programs during the third quarter and had a substantial presence at the World Sleep Conference in September with 15 posters and for oral presentations across our sleep portfolio.

As an R&D organization, we are focused on becoming a global leader and partner of choice with the goal of bringing novel differentiated therapies to patients through focused discovery and development and expanding the value of our commercial portfolio.

Our ability to bring in innovative technologies.

Coupled with our drug development expertise and Executional excellence are critical to building advancing a high value and sustainable pipeline.

I'll begin with development activities at our sleep there are signs therapeutic area, starting with JCP to five eight.

We've been working since 2012 to develop a novel Oxybate formulation that would reduce the sodium load.

Patients get would xyrem, while still delivering the efficacy that has made xyrem such an important option for narcolepsy patients.

These efforts led to a successful development program with JCP to Fiveeight.

Rob: These efforts led to a successful development program with JCP 258, a product candidate that resulted in one to one and a half grams less sodium per night than Zyra. We're very pleased with the recent presentation of the positive Phase 3 study results and the strong, encouraging interest from healthcare providers to date, including physician feedback noting the importance of a low-sodium treatment option for the management of narcolepsy patients. Narcolepsy is a chronic, lifelong disease and is associated with increased cardiovascular risk.

Product candidates that resulted in one to one that I have grams less sodium per night and xyrem.

We're very pleased with the recent presentation of the positive phase three study results and the strong encouraging interest from health care providers to date.

Including physician feedback, noting the importance of low sodium treatment option for the management of narcolepsy patients.

Narcolepsy as a chronic lifelong disease and its associated with increased cardiovascular risk.

Rob: JCP is a priority program for us, and we believe it will be a clinically meaningful option for all narcolepsy patients. We are incorporating feedback from our recent pre-NDA meeting with the FDA and expect to submit our NDA in January, followed by their acquisition of Cavion in August. We're excited to broaden our neuroscience therapeutic focus to movement disorder. Cavion completed a Phase II randomized placebo-controlled proof-of-concept study with CX8998, now called JZP385, a small-molecule modulator of T-type calcium channels for the treatment of patients with essential tremors. Kavion's Phase 2 study utilized an initial exploratory formulation of JZP385.

JCP as a priority program for us and we believe it will be a clinically meaningful option for all narcolepsy patients.

We are incorporating feedback from our recent pre NDA meeting with the FDA and expect to submit our India in January .

With our acquisition of caveat in August .

We're excited to broaden our neuroscience therapeutic focus into movement disorders.

Caveat uncompleted a phase two randomized placebo controlled proof of concept study with CX 8998, now called JCP 385.

Small molecule modulator of T. type calcium channels for the treatment of patients with essential tremor.

Caveats phase two study utilized and initial exploratory formulation of JCP 385.

Rob: We have begun commercial formulation optimization work as we continue our efforts to enhance the target profile of JCP 385 and plan to use this optimized formulation in our Phase 2B study, which we expect to initiate next year. Now, turning to our hematology-oncology development activities, I'll begin with Vixios. The development program for VIXIOS is progressing well. During the third quarter, patient enrollment began in two key cooperative group studies. One in newly diagnosed adult patients with intermediate and high-risk AML with the AMLSG Cooperative Group, and the second study in high-risk MDS, also known as Paloma, with the European Myelodysplastic Syndrome Cooperative Group.

We have begun commercial formulation optimization work as we continue our efforts to enhance the target profile JCP 385.

And plan to use this optimized formulation in our phase Twob study, which we expect to initiate next year.

Now turning to our hematology oncology development activities I'll begin with Vyxeos.

The development program for Vyxeos is progressing well.

During the third quarter patient enrollment initiated in two key co-operative proved studies.

One in newly diagnosed adult patients with intermediate and high risk came out with the M.L. SG Cooperative group in the second study in high risk Mds also known as Paloma with the European Myelodysplastic syndromes.

Cooperative group.

Rob: Last month, we also enrolled the first patient in a Phase 1B study evaluating low-intensity therapy Vixios in combination with venetoclax in first-line, unfit AML. And we are also making progress to activate sites in the fourth quarter for our phase 1B master trial to evaluate Vixios combinations and fit patients with previously untreated AML. This master trial will be a multi-center, multi-armed, non-randomized trial of VIXIOS administered in combination with various targeted agents, including venetoclax, midisturin, and inacidentib.

Last month, we also enrolled the first patient phase one be study evaluating low intensity therapy vyxeos in combination with Venetoclax in first line unfit AML.

And we're also making progress to activate sites in the fourth quarter for phase one be master trial.

Are you a vyxeos combination and fit patients with previously untreated AML.

Master trial will be a multicenter multi arm non randomized trial vyxeos administered in combination with various targeted agents, including Veneta KLAX fit historian and inadequate.

And NASA Dennis.

Rob: Our global defibrillator program also continues to advance. Last month, we announced the enrollment of the first patient in our exploratory phase two study evaluating defibritide for the prevention of CAR T-associated neurotoxicity. We also recently completed enrollment in the Phase 2 prevention of acute GVHD study, and we expect initial top-line results in the second half of 2020. In the prevention of VOD Phase 3 study, we expect to complete the interim analysis of the first 280 patients and reach enrollment of 400 patients in the first half of 2020. This interim analysis will allow us to determine whether to continue enrollment beyond 400 patients, up to a maximum of 600 patients per our predefined adaptive design, or to stop the study for efficacy or futility. We are focused on optimizing the value of our portfolio by balancing projects within and across therapeutic areas, including the rigorous criteria we set for advancing or stopping some projects. With this in mind, we have prioritized defibritide studies focused on prevention of VOD, acute GVHD, and CAR T-associated neurotoxicity.

Our global Defibrotide program also continues to advance.

Last month, we announced the enrollment of the first patient and our exploratory phase two study evaluating defibrotide for the prevention of car T ceded neurotoxicity.

We also recently completed enrollment in the phase two prevention of acute Gvhd study.

And we expect initial topline results in the second half of 2020.

In the prevention of via the Phase three study, we expect to complete the interim analysis of the first 280 patients and reach enrollment of 400 patients in the first half of 2020.

This interim analysis will allow us to determine whether to continue enrollment beyond 400 patients.

Up to a maximum of 600 patients per our pre defined adaptive design.

Or to stop the study for efficacy or futility.

We are focused on optimizing the value of our portfolio by balancing projects within and across therapeutic areas.

Including the rigorous criteria, we set for advancing or stopping some projects.

With this in mind, we have prioritized the Defibrotide studies focused on prevention of Q TV ads, sorry prevention of Vo D.

Acute gvhd and car T associated neurotoxicity.

Rob: And we have made the decision to discontinue our transplant-associated thrombotic microangiopathy activity. Now, turning to our asparaginase program. The JCP 458 study protocol has been finalized, and we expect to activate sites with the goal of beginning enrolling patients with ALL and LBL this year. The study will be a single-arm pivotal phase 2-3 study enrolling approximately 100 patients with a planned interim analysis of approximately 50 patients. I am pleased with our progress on JZP 458 to date, moving from an IND in Q4 2018 to starting our pivotal study in Q4 2019. We expect potential completion of study enrollment by fourth quarter 2020, and assuming positive results, the BLA submission will be our top priority. We look forward to providing this important treatment option to patients as soon as possible. Lastly, we look forward to having a strong presence at the American Society of Hematology meeting to be held in December. 15 abstracts across our He-Monk portfolio and an update from our partner Immunogen on the IMGN 632 program

And we have made the decision to discontinue our transplant associated thrombotic microangiopathy activities.

Now turning to our Asparaginase program.

The JCP four or five eight study protocol has been finalized and we expect to activate sites with the goal to begin enrolling patients with AOL and LPL this year.

The study will be a single arm pivotal phase two three study.

Enrolling approximately 100 patients for the planned interim analysis at approximately 50 patients.

I'm pleased with our progress on JCP five.

Four or five eight to date.

Moving from an I'd and fourth quarter 2018, starting a pivotal study in fourth quarter 2019.

We expect potential completion of study enrollment by fourth quarter 2020, and assuming positive results. The BLA submission will be our top priority.

We look forward to providing this important treatment option to patients as soon as possible.

Lastly, we look forward to having a strong presence at the American Society of Hematology meeting to be held in December .

15 abstracts across our human portfolio.

And an update from our partner Immunogen on the I am GE and 632 program.

Bruce C. Cozadd: I'll now turn the call back over to Bruce for the financials. Thanks, Rob. Before I review our financial results, I want to publicly thank Matt Young for his six years of contributions to Jazz and to wish him all success in his new expanded role at Grail. In the third quarter, we delivered strong 15% year-over-year revenue growth. Even with increased investments to support our R&D programs and product launches, we generated adjusted net income as a percent of top-line revenues of over 40% and strong cash flow. Our financial performance positions the company for continued growth in 2020 and beyond, with revenue growth for 2019 ahead of our expectations. We are increasing our total revenue guidance for 2019 to a range of $2.1 to $2.18 billion, an increase of 11 to 15 percent over 2018. Turning to our key products, we're increasing our 2019 Xyrem Net Sales Guidance to a range of $1.60 to $1.64 billion and are maintaining our expectation for mid-single-digit volume growth. Total Xyrem net sales growth is expected to be between 14 and 17 percent for 2019. However, Erwin A's net sales for the quarter were impacted by limited product availability.

I'll now turn the call back over to Bruce for the financial update.

Thanks, Rob.

Before I review, our financial results I want to publicly thank Matt young for his six years of contributions to jazz and tuition all success in his new expanded role at Grail.

In the third quarter, we delivered strong 15% year over year revenue growth.

Even with increased investments to support our R&D programs and product launches, we generated adjusted net income as a percent of topline revenues of over 40% and strong cash flow.

Our financial performance positions the company for continued growth in 2020 and beyond.

With revenue growth for 2019 ahead of our expectations, we're increasing our total revenue guidance for 2019, two range of $2.1 billion to $2.18 billion, an increase of 11% to 15% over 2018.

Turning to our key products, we're increasing our 2019 xyrem net sales guidance to a range of 1.6, so to $1.64 billion and are maintaining our expectation for mid single digit volume growth.

Total xyrem net sales growth is expected to be between 14 and 17% for 2019.

Irwin as net sales for the quarter were impacted by limited product availability. However, we are maintaining our previous Irwin as net sales guidance as it anticipated a level of supply disruption.

Bruce C. Cozadd: However, we are maintaining our previous Erwin A net sales guidance as it anticipated a level of supply disruption. We've narrowed our Defitelio and Vixios Net Sales guidance ranges to $160 to $180 million and $120 to $135 million, respectively. Now we'll turn to Operating Expenses. We have been intentionally increasing SG&A expenses to support the Synosy U.S. launch and future EU launch, as well as the Vixios US Salesforce expansion and continued EU launch. Adjusted SG&A guidance for 2019 remains 29 to 31 percent of total revenue. Adjusted R&D expenses in the quarter increased to 14% of revenues and reflect our commitment to building and advancing our development pipeline.

We've narrowed our defitelio and Vyxeos net sales guidance ranges to $160 million to $180 million and $120 million to $135 million respectively.

Now I'll turn to operating expenses, we have been intentionally increasing yesterday expenses to support the sonos the U.S. launch and future you launch as well as the Vyxeos U.S. Salesforce expansion and continue to you launch.

Adjusted EBITDA guidance for 2019 remains 29% to 31% of total revenues.

Adjusted R&D expenses in the quarter increased to 14% of revenues and reflect our commitment to building and advancing our development pipeline.

Bruce C. Cozadd: Adjusted R&D guidance for the full year remains 11-13% of total revenue. These investments in the business are critical to fueling our future growth. As we move into 2020, we expect to thoughtfully ramp up and prioritize our investment. Key Value Drivers, which include supporting future product launches, such as Finosi in the EU, JCP 258 and JCP 458, and advancing our R&D programs as well as expanding the portfolio through corporate development activities. Our tax provision and effective tax rate for the third quarter on both a gap and non-gap basis were favorably impacted by the release of reserves upon the expiration of a statute of limitations during the. As a result, we are updating our 2019 Adjusted Adjusted Tax Rate guidance to a range of 14 to 16. Additionally, we are increasing our 2019 non-GAAP adjusted EPS guidance to a range of $15.50. $16.15, an increase of 13-18% compared to 2018. In the third quarter, we saw strong cash generation from operations of $338 million, and as of September 30, we had $1.1 billion in cash and investments.

Adjusted R&D guidance for the full year remains 11% to 13% total revenues.

These investments in the business are critical to fueling our future growth as we move into 2020, we expect to thoughtfully ramp and prioritize our investments in key value drivers, which includes supporting future product launches such as sonos the in the EU.

JCP to 58, and JGB for 58, and advancing our R&D programs as well as expanding the portfolio through corporate development activities.

Our tax provision an effective tax rate for the third quarter on both a GAAP and non-GAAP basis were favorably impacted by the release of reserves upon the expiration of the statute of limitations during the quarter.

As a result, we are updating our 2019 adjusted effective tax rate guidance to a range of 14% to 16%.

We are increasing our 2019 non-GAAP adjusted EPS guidance to range of $15 in 50 cents to $16 in 15 cents, an increase of 13% to 18% compared to 2018.

In the third quarter, we saw strong cash generation from operations $338 million and as of September 30 had 1.1 billion in cash and investments as of September 30, the remaining amount authorized under our current share repurchase program was $188 million and last week, our board of directors increase.

Bruce C. Cozadd: As of September 30, the remaining amount authorized under our current share repurchase program was $188 million, and last week, our Board of Directors increased our existing share repurchase program authorization by an additional $500 million. To wrap up, I'm excited about the progress and strong execution in 2019 and the growth opportunities ahead for Jazz. We're focused on delivering strong financial performance through an expanded commercial portfolio, continued diversification of our sleep and neuroscience pipeline, and continued advancement of our hematology-oncology early and late-stage development program. This quarter, we look forward to continuing our efforts to rapidly progress our novel product candidates, JCP 258 and JCP 458, which have the potential to fundamentally change the lives of patients. With $2.7 billion in readily available capital, we will continue to invest in our business and pursue a broad range of attractive corporate development opportunities to provide attractive long-term returns for shareholders. Thank you for joining us today.

The star existing share repurchase program authorization by an additional $500 million.

To wrap up I'm excited about the progress and strong execution in 2019 and the growth opportunities ahead for jobs, we're focused on delivering strong financial performance through an expanded commercial portfolio continued diversification of our sleep and Neurosciences pipeline and continued advancement of our hematology oncology early.

Late stage development programs.

This quarter, we look forward to continuing our efforts to rapidly progress or novel product candidates JCP to 58 and James It before 58, what the potential to fundamentally change the lives of patients with $2.7 billion and readily available capital. We will continue to invest in our business and pursue a broad range of attractive corporate develop.

And opportunities to provide attractive long term return for shareholders.

Thank you for joining us today, I'll now turn the call over to count.

Thanks, Bruce we kindly request that you limit yourself to one question. During this call. So that everyone will have the opportunity to ask a question. We will gladly address any additional questions either after the call or you can reenter the queue with that said operator. Please open the line for questions.

Thank you and as a reminder to ask a question do we need to press the star one one of your telephone.

Unknown Executive: I'll now turn the call over to you, Bruce. I would kindly request that you limit yourself to one question during this call so that everyone will have the opportunity to ask questions. We will gladly address any additional questions either after the call or you can reenter. With that said, operator, please open the line for questions. Thank you, and as a reminder to ask a question, you will need to press the star 1 on your telephone. To withdraw your question, please press the pound key.

To withdraw your question. Please press the pound key please stand by weaker pound the Q and a roster.

And our first question comes from the line of Brendan folks with Cantor Fitzgerald. Your line is now open.

Hi, Thanks for taking my question.

Can you just talked about the market dynamics that you have seen in democracy cyren since to try to send came to market and perhaps elaborate on and the Patel descent labeling with not having cataplexy and then they do how could this differentiate sorry, okay. Thank you.

Unknown Executive: Please stand by while we compile the Q&A roster. And our first question comes from the line of Brandon Folkes with the Cancer Refrigerator. Your line is now open. Hi, thanks for taking my question. Can you just talk about the market dynamics that you are seeing in the market with Xyrem since Patoliscent came to market and perhaps elaborate on the Patoliscent label and, with it, not having cataplexy in the label, how could this differentiate Xyrem long-term?

Well Brandon.

Well patrol Sam got approved in August they said they were launching in the fourth quarter and so the results you're seeing from US don't include any impact.

A toll ascent being on the market.

In terms of their label.

You're right that we have a different label we have a label that's for the treatment of cataplexy and he vs and narcolepsy, both in children and adults.

We then you know the the gold standard treatment for a long time.

And we think many patients that are on Xyrem are actively benefiting from this most effective therapy.

Bruce C. Cozadd: Well, Brandon, you know, while Petolisamp got approved in August, they said they were launching in the fourth quarter. And so the results you're seeing from us don't include any impact of Patola Stant being on the market. In terms of their label, you're right that we have a different label.

Of course, we recently introduced another product for the treatment of narcolepsy Essen narcolepsy.

As well as he has to know essay and Sanofi and we're excited for people to gain experience with that product as well.

With that I'll just add Bruce this is Dan.

As we look forward to finishing the year strong.

Bruce C. Cozadd: We have a label that's for the treatment of cataplexy and EDS and narcolepsy, both in children and adults. We've been the gold standard treatment for a long time. And we think many patients that are on Xyrom are actively benefiting from this most effective therapy. Of course, we recently introduced another product for the treatment of narcolepsy, EDS and narcolepsy, as well as EDS and OSA, and CENOSI, and we're excited for people to gain experience with that product. One thing I would just add, Bruce, this is Dan, as we look forward to finishing the year strong, we have raised our guidance. There's opportunity for growth both in volume and revenue for the Xyro. Thank you. Thank you. And our next question comes from the line of Esther Rajavelu with Oppenheimer. Your line is now open. Thank you for taking my question. I just had a quick one on Cynosi.

We've raised our guidance and we continue to believe there's opportunities for growth.

Growth both in volume and revenue for Xyrem franchise.

Great. Thank you.

Thank you.

And our next question comes from the line of Esther Russia value with Oppenheimer. Your line is now open.

Thank you for taking my question I just had a quick one on on snow see in the U.S. How is okay. You see seen for Sanofi with regards to.

Between the two indications and are you seeing more used to treatment naive patients.

Folks switching from other medications to Sanofi and then if I can squeeze one more in a market chatty chain Europe questionnaires CAC and looking into next year.

Yeah, maybe I'll ask Mike to talk a little bit about what we're seeing in the early days of the snow see US launch and then maybe Dan can take the European piece sure Bruce.

It is early we're excited I'm pleased with what we have seen so far in the launch.

It with a retail launch you don't get the showing the diagnosis every script. So we have to go back and and actually do some primary research. Our initial primary research has indicated it's about 50 50, I wish I had narcolepsy.

Mike: In the U.S., what kind of use are you seeing for Cynosi with regard to the two indications, and are you seeing more use in the treatment of naive patients or folks switching from other medications to Cynosi? And then, if I can squeeze one more in, the market strategy in Europe for Cynosi as you're looking into next year. Yeah, maybe I'll ask Mike to talk a little bit about what we're seeing in the early days of the Sonosy US launch, and then maybe Dan can take to your... Sure Bruce, it is early, we're excited and pleased with what we have. So far in the launch, with a retail launch, you don't necessarily get the diagnosis of every script. So we have to go back and actually do some primary research. Our initial primary research has indicated that it's about 50-50 OSA and narcolepsy. That is not surprising given our beachhead strategy was to go after our narcolepsy targets early on and then fan out to a broader OSA-treating audience, which we are in the process of doing. Largely, the strength breakout is about 50%, 75%, 50%, and 150%.

That that it's not surprising given our beachhead strategy was to go after our narcolepsy targets early on and then fan out to a broader oh, a shade treating audience, which we are in the process of doing.

Is largely the strength break out it's about 50% 70, 550% 150.

And again, we feel good about the.

Metric so far.

And on treatment naive or having been on other agents most patients in this space have tried other therapies and again I don't think we've got specific data since launch quantitative data on that but.

Our belief is that you know many patients have tried multiple other agents.

Our looking for something that provides a differential treatment.

Dan on your yeah. So on Europe , I'm very excited for Sanofi to be meaningful growth driver in Europe than.

The cornerstone as a new franchise for us outside the U.S. as we move into sleep dinner assigns.

In terms of the focused today, that's been obviously on the approval and move into the regulatory process.

Dan: And again, we feel good about the..., and Metrics, so forth. And whether they are treatment naive or have been on other agents, most patients in this space have tried other therapies. And again, I don't think we've got specific data since launch, quantitative data on that. But our belief is that, you know, many patients have tried multiple other agents and are looking for something that provides a differential, Dan in Europe. Yeah.

Importantly, the market dynamics are a little bit different in Europe , where particularly I'd say there is no treatment option for the treatment of DDS.

So we've been focused this year on a medical education and preparing.

Okay wells and others for the opportunity.

In terms of priority, we're going to focus on three of the biggest countries first.

Dan: So on Europe, you know, very excited for Sanofi to be, you know, a meaningful growth driver in Europe, the cornerstone of a new franchise for us outside the U.S. In terms of the focus to date, it's obviously been on approval and moving through the regulatory process. Importantly, the market dynamics are a little bit different in Europe where, particularly in the USA, there is no treatment option for the treatment of EDS.

Which will be Germany, France, and the UK.

And in terms of timing, probably Germany will or will be the biggest focus for next year, where there's more opportunity to go faster on the market access side.

Great. Thank you.

Thank you and our next question comes from the line of Ami Fadia with SVB Leerink. Your line is now open.

If your phone is on new please UN mute.

Sorry can you help me okay now.

Yes, we hear you okay great.

Thanks for taking the question.

Dan: So, we've been focused this year on medical education and preparing KOLs and others for the opportunity. In terms of priority, we're going to focus on three of the biggest countries first, which will be Germany, France, and the UK. And in terms of timing, probably Germany will be the biggest focus for next year, where there's more opportunity to go faster on market activity. Great, thank you. Thank you. And our next question comes from the line of Ami Fadia with SVB Lyric. Your line is now open. If your phone is on mute, please unmute it.

Can you talk to how sustainable these items growth is.

Your guidance you revised guidance suggests a little bit stepped down in fourth quarter versus third quarter, a is that reflective of the additional competition you anticipate.

And you know how should we read thinking about sort of next year's growth. If you can just stuck to that qualitatively at least.

And maybe if I could just squeeze in another question just on other than knees. You know why did you develop your own set us up your on prop product as a place or a supplement over needs. So can you give us an update on your negotiations to extend the contract. Thank you.

Bruce C. Cozadd: Sorry, can you hear me okay now? Okay, great. Thanks for taking the question. Can you talk about how sustainable Xyrem growth is?

Bruce C. Cozadd: Your guidance, your advice, suggests... a little bit of a step down in the fourth quarter versus the third quarter. Is that reflective of the additional competition you anticipate? And, you know, how should we be thinking about sort of next year's growth? If you can just talk about it qualitatively, at least.

Yeah, let me on the sustainability of Xyrem growth as I said in my script comments.

We absolutely believe there's continued growth in Xyrem, we do have a little bit wider range as we approach. The ended this year for reasons I think we detailed in our last call.

Bruce C. Cozadd: And maybe I could just squeeze in another question just on UrbanAce, you know, while you develop your own sort of your own product to replace or supplement UrbanAce, can you give us an update on your negotiations to extend the contract? Thank you. Yeah, Ami, on the sustainability of Xyrom growth, as I said in my script comment, We absolutely believe there's continued growth in Xyrom. We do have a little bit wider range as we approach the end of this year for reasons.

Namely we've got a sales force this now detailing to products not one product, we've got multiple new entrants in the space, including our own Sanofi as well as.

Potentially portola sand.

And so we wanted to give ourselves a little more room. There I also indicated that we did sign an agreement with related to Xyrem access and the wall that won't have a major impact on the fourth quarter, that's built into our guidance as well, but the main thing to take away is we continue to feel narcolepsy is under diagnosed and undertake.

Bruce C. Cozadd: I think we detailed in our last call, namely, we've got a sales force that's now detailing two products, not just one product. We've got multiple new entrants in the space, including our own Synosy, as well as potentially Patolisant, and so we wanted to give ourselves a little more room there.

Got it.

We're looking forward to continuing to get that message out there the availability of other treatment options may in fact create more noise in the marketplace, we'd love to see more patients.

With narcolepsy get treated so we're looking forward to.

Bruce C. Cozadd: I also indicated that we did sign an agreement related to Xyrom access and that while that won't have a major impact on the fourth quarter, that's built into our guidance as well. But the main thing to take away is that we continue to feel narcolepsy is underdiagnosed and undertreated. We're looking forward to continuing to get that message out there. However, the availability of other treatment options may, in fact, create more noise in the marketplace.

Near term growth with Xyrem, we're looking forward to bringing to 58 to the market.

As we believe and even improved a treatment option and continuing to grow this franchise overtime.

Not going to say anything more specifically about 2020 at this point, we usually give guidance as we come into our fourth quarter results early next year.

On Irwin A's.

We are continued to engage with PBL.

Current manufacturer in the process, they're running to figure out who will be.

Bruce C. Cozadd: We'd love to see more patients with narcolepsy get treated, so we're looking forward to near-term growth with Xyrom. We're looking forward to bringing 258 to the market as we believe in even better treatment options and continuing to grow this franchise over time. I'm not going to say anything more specifically about 2020 at this point; we usually give guidance as we come into our fourth quarter results early next year. On Erwin A's, we continue to engage with PBL, the current manufacturer, in the process, until the expiration of our deal.

The market or if that product post.

The expiration of our deal we continue to feel we'd be an excellent partner, but.

That process is not yet complete.

Thank you and our next question comes on line of Gary Nachman with BMO capital markets. Your line is open.

Thanks onto five eight now that you expect approval in the second half of next year any comments launch plans and how you will try to manage the overall franchise with Xyrem.

And then any update on the once nightly low sodium formulation and how soon you might be able to progress into either phase two or phase three with that thank you.

Bruce C. Cozadd: We continue to feel we'd be an excellent partner, but that process is not yet completed. Thank you. And our next question comes from the line of Gary Nachman with BMO Capital Markets. Your line is now open.

Yes, Gary I'll take the second part of your question first which is we don't have any new updates around the once nightly program. We do remain interested in that as a future.

Bruce C. Cozadd: Thanks. On 258, now that you expect approval in the second half of next year, any comments on launch plans and how you'll try to manage the overall franchise with Xyrem? And then, any update on the once nightly low sodium formulation and how soon you might be able to progress into either phase two or phase three with that? Thank you. Yeah, Gary, I'll take the second part of your question first, which is we don't have any new updates for the Once Nightly program.

Potential product, but right now we're focused on 258 and getting that to market.

In terms of launch plans not a lot to say right now.

As you know, we just said we submit the M.D.A. ER and the very early part of next year with the PRB.

And then we'll look forward to bringing it to market. It's important to note that we think all.

Patients can benefit all oxybate patients can benefit from the significantly reduced sodium load remember this chronic lifelong medication.

Bruce C. Cozadd: We do remain interested in that as a potential future product. But right now, we're focused on 258 and getting that to market. In terms of launch plans, not a lot to say right now. As you know, we just said we'd submit the NDA in the very early part of next year with the PRV. And then we'll look forward to bringing it to market. It's important to note that we think all patients can benefit. All octobate patients can benefit from the significantly reduced sodium load. Remember this is a chronic, lifelong medication and that narcolepsy patients, on average, have, you know, significant cardiovascular risk factors.

And that narcolepsy patients on average have.

Significant cardiovascular risk factors and so.

That's substantial reduction in daily sodium intake, we think will be significant across that patient population.

Okay. Thank you.

Thank you and our next question comes from a cash to worry with Wolfe Research. Your line is an open.

Hey, thanks, so much so firstly just wanted to yet I understand a bit on what's going on with Vyxeos. It seemed to be down sequentially and you brought down the lower the top end of the guidance. So how much of the 30 million figure is in the U.S. risk to the ex U.S. and kind of what's the growth cadence been like and both of those territories and maybe.

Bruce C. Cozadd: And so, that substantial reduction in daily sodium intake we think will be across that patient population. Okay, thank you. Thank you. And our next question comes from Akash Tewari with Wolf Research. Your line is now open. Hey, thanks so much. So firstly, just wanted to understand a bit about what's going on with VIXEO. So it seemed to be down sequentially, and you brought down the lower end of the guidance.

Did more strategically I, just maybe your comments on Abdel and its once nightly program.

It looks like the trial should read out sometime next year.

Is that.

He possibility from a BD perspective for jazz you guys have interest in a one slightly program. If they show data that you know seems kind of interesting could this be something that jazz could look to acquire or do you think there may be FTC considerations that would kind of make that not possible. Thanks. So much.

Bruce C. Cozadd: So how much of the 30 million figure is in the US versus the ex-US and kind of what's the growth cadence been like, and both of those territories, and maybe a bit more strategically, just maybe your comments on Avidel and its one slightly different program. It looks like the trial should read out sometime next year. Is that a possibility from a BD perspective for jazz?

Yeah on your Vyxeos question, while we don't provide specific break down of U.S. versus ex US sales, we did say coming into the year, we thought Europe could account for 10% or so of our Vyxeos revenues were actually ahead of schedule on that we're really pleased with the early.

Bruce C. Cozadd: You guys have an interest in a slightly different program? If they show data that seems kind of interesting, could this be something that Jazz could look to acquire? Or do you think there may be FTC considerations that would kind of make that not possible?

Experience with the Vyxeos you launch.

Bruce C. Cozadd: Thanks so much. Yeah, on your VIXIOS question, while we don't provide a specific breakdown of U.S. versus ex-U.S. sales, we did say coming into the year that Europe could account for 10% or so of our VIXIOS revenues. We're actually ahead of schedule on that.

You know in terms of growth.

I think.

We pointed out on this call that the expanded Vyxeos salesforce and the U.S. was trained in the third quarter, but started their promotional activities. This quarter. We're looking forward to seeing what they can do over time, particularly as we do a better job of covering the community accounts.

Bruce C. Cozadd: We're really pleased with the early experience with the VIXIOS EU launch. You know, in terms of growth, I think we pointed out on this call that the expanded Vixio sales force in the U.S. was trained in the third quarter but started their promotional activities this quarter. We're looking forward to seeing what they can do over time, particularly as we do a better job of covering the community. So we're excited to see what that produces. On your question about the Avidel program, you know, in keeping with past practice, we really don't comment on specific business development opportunities, so I'm going to, I'm going to decline to answer there. We're, of course, interested to see their data on what changing the PK profile of oxabate does, admittedly, in this case, in a sort of higher sodium version, but we'll be interested to see what that does, in fact, produce, and we'll be watching that along with all of you.

So were.

Excited to see what that produces on your question on the Abdel program.

Keeping with past practice, we really don't comment on specific.

BD opportunities, so I'm going to.

Declined to answer there were of course interested to see their data.

On what a change in the PK profile.

Of Oxybate does admittedly in this case and in a sort of higher sodium version.

But we'll be interested to see what that does in fact produce and Ah I will be we'll be watching that along with all of you.

Great. Thanks, so much really appreciate it.

Thank you and our next question comes from the line of Jason Gerberry with Bank of America. Your line is an open.

Hi, Thanks for taking my questions.

Just one sticking with the FTC theme on GDP, four or five aided theres scenario, where you can renew your deal with PBL and also bring JCP four or five eight into the broader umbrella of products that are sold by by jazz or would you be prevented from selling both do you get to a point once you commence in phase three where you.

Bruce C. Cozadd: Great. Thanks so much. I really appreciate it. Thank you. And our next question comes from the line of Jason Gerberry with Bank of America. Your line is now open. Hey, thanks for taking my questions. Just one sticking with the FTC theme. On JCP 458, is there a scenario where you can renew your deal with PBL and also bring JCP 458 into the broader umbrella of products that are sold by Jazz, or would you be prevented from selling both? Do you get to a point once you commence in Phase 3 where you can't renew with PBL? Just sort of curious about that dynamics, how that works.

Can't renew with PBL, just sort of curious about those dynamics, how that works and then secondly, just on GDP to five eight any important areas now that you have the data where you think you can differentiate from a labeling perspective relative to xyrem. Thanks.

Yes. So on your first question, we have every intent of bringing a new recombinant are winning asparaginase product to market.

We absolutely think there's room to do that I remember the worldwide market is underserved right now.

Bruce C. Cozadd: And then secondly, just on JCP 258, any important areas now that you have the data where you think you can differentiate from a labeling perspective relative to Xyrem? Thanks. Yeah, so on your first question, we have every intention of bringing a new recombinant Erwinia asparaginase product to market. We absolutely think there's room to do that. Remember, the worldwide market is underserved right now. For example, Irwin-Ace is actually approved in Japan and has not yet been launched because there's been an inability to supply that market. So, you know, the ability to get asparaginase to all patients who need it around the world, and to resume our more focused promotional efforts on ensuring that all patients who might benefit are offered this option, including adolescent and young adult patients. Taking another look at silent inactivation and even exploring clinically potential broadened use of asparaginase beyond ALL.

For example, or when A's is actually approved in Japan, and not yet launched.

Because there's been an inability to supply that market. So you know the ability to get a asparaginase base to all patients who need it around the world.

To resume are more focused promotional efforts on ensuring that all patients who might benefit our are offered this option, including adolescents and young adult patients taking another look it's a silent and activation.

And even exploring clinically potential broaden useful disparaging nice beyond AOL I think theres a lot we can do.

With that on to 58, I don't think we're going to comment specifically on our labeling strategy. Obviously, there will be differences in the label to be sure.

Starting with the very different sodium content.

Bruce C. Cozadd: I think there's a lot we can do. With that on 258, I don't think we're going to comment specifically on our labeling strategy, Obviously, there will be differences in the label, to be sure, starting with the very different sodium content, which is, of course, noted and called out in several ways in our existing Xyron label, but more to come on that after we have had a chance to get that submission in and work with FDA to get to a final product. Great, thank you. Thank you. And our next question comes from the line of David Amsellem with Piper Jaffray. Your line is now open. Thanks. So on CENOSI with the Tier 2 WIN for ESI, I just want to clarify that that is without any restriction of step-throughs through the generic modafinil or armadafinil, I guess with a Tier 2 win, and to the extent that there are others, you know, how does that change how you're thinking about gross to net, or did your initial expectations around gross to net contemplate, Yeah, David, to the first part of your question, that tier two status is with a step through of one generic agent that's consistent with what we guided to pre-launch.

Which is of course noted and called out in several ways in our existing xyrem label, but but more to come on that.

After we have had a chance to get that submission and and work with F.D.A. too to get to a final product label.

Great. Thank you.

Thank you and our next question comes from the line of David and sell them with Piper Jaffray. Your line is now open.

I think so on some no see with the the tier to win for yes, I just want to clarify that that is without any restriction of stepped throughs through the generic definite alarm indefinite idle and.

I guess with say a tier two when and to the extent that there are others.

How does that change how you're thinking about gross to nets or did your initial expectations around gross than that comp contemplate.

This call these kind of formulary wins thanks.

Yes, David.

The first part of your question that tier two status is with a step through of one generic agent that's consistent with what we guided to pre launch similarly, the gross to net comments, we made on our prelaunch called did anticipate the strategy we're employing.

Bruce C. Cozadd: Similarly, the gross to net comments we made on our pre-launch call did anticipate the strategy we're employing. Okay, thanks. Thank you. And our next question comes from the line of Umar Rafat with Evercore.

Okay. Thanks.

Thank you and our next question comes from the line of Umer Raffat with Evercore. Your line is no.

Bruce C. Cozadd: Your line is now open. Hi, thanks so much for taking my question. Bruce, I'm curious to get your take on the recent Takeda data on their narcolepsy drug. I realize it's an IV form, and they might have orals as well, but I was curious to hear how you guys looked at it and how the clinician community was sharing feedback.

Hi, Thanks, so much for taking my question Bruce I'm curious to get your take on the recent Takeda data on their narcolepsy drug I realize it's an ivy form and they might have a world as well, but I was curious to hear how you guys looked at it and how the clinician communities here and feedback with you.

Yeah, I think it's exciting that there's a new mechanisms mechanism of action being pursued this is one that I would say.

Bruce C. Cozadd: Yeah, I think it's exciting that there's a new mechanism of action being pursued. This is one that I would say many folks in the KOL community and SLEEP have long been interested in, and this is really the best data people have seen with this approach. We're watching it with interest, and uh... we're committed to maintaining a leadership position uh... in the sleep space over time, so we're you know we're looking at this as well as all approaches people are taking to uh... address more serious Well, I think we're a long way from phase one to, you know, what the competitive impact will be years from now. Let's continue to watch the data, and, as you yourself noted, I don't think uh... Ivy is likely the way this ends up. I think that's an early step along their product development evolution, so let's watch that. Thank you very much. Thank you. And our next question comes from the line of Greg Gilbert with SunTrust. Your line is now open. Thanks. Good afternoon, How much of Xyrem use is in patients with cataplexy, if you have any research on that?

Many folks in the K, a well community and sleep.

Have long been interested in.

And this is really the best state of people have seen a with this approach.

We're watching it with interest and.

We remain committed to maintaining a leadership position.

In the sleep space over time. So we're we're looking at this as well as all approaches people are taking to.

Address more serious sleep disorders, but I thought.

For for early data with that age and it was it was really impressive.

Do you think it impacts jazz franchise down the road.

Well I think we're a long way from phase one too you know what the competitive impact will be years from now let's continue to watch the data.

And as you yourself noted I don't think I'd is likely the the way. This ends up I think that's an early step along there.

Product development evolution, so let's watch that continue.

Thank you very much.

Thank you and our next question comes from the line of Gregg Gilbert with Suntrust. Your line is now open.

Thanks, Good afternoon, how much of Xyrem use is in patients with cataplexy. If you have any research on that and then secondly, how would you characterize the technical risk you see for four or five eight.

Bruce C. Cozadd: And then secondly, how would you characterize the technical risk you see for 458? And what's the earliest you could get it to market, assuming the interim data point is positive and fileable? Thanks. So, how much of the use is it in patients with cataplexy? You know, when you're asked what percentage of narcolepsy patients have cataplexy, the estimates vary pretty widely. I think, most likely, you will hear a range of 60% to 100%. And whenever I hear somebody say a range that includes 100%, I always stop and say, it seems to me it's either 100% or it's not, how can there be a range that includes 100%, but what we hear from patients and what we hear from treaters is that sometimes cataplexy goes unrecognized.

And what's the soonest, you could get it to market assuming the interim data points is positive and file a ball.

Thanks.

So on how much of the uses in patients with cataplexy.

When you when you're asked what percentage of narcolepsy patients have cataplexy the.

The estimates vary pretty widely I think most likely you hear a range of 60% to 100%.

And whenever I hear somebody say a range that includes a 100% I always stop and say seems to me, it's either 100% or it's not how can there be arrange that includes a 100%, but what we hear from patients on what we hear from treaters I is the sometimes cataplexy goes.

Bruce C. Cozadd: And it's an amazing thing when you think about this symptom, which is a loss of muscle tone in response to an emotional stimulus, you'd think either you have it or you don't, but what we find is that patients who are ultimately successfully diagnosed with narcolepsy, when asked about cataplexy in terms that they understand, like... Do your knees ever buckle when you hear a joke? Do your cheeks ever sag when you're feeling emotional? They will say, oh, yes, that's been true for years. And when asked, did you ever mention that to your doctor? The response is often, I did mention that to my doctor, it's just that weird thing that always happens to me so, Long answer, but it's unclear as to whether there are a large group of patients that just don't experience cataplexy at all or whether it's cataplexy that hasn't yet been noticed and pointed out.

Unrecognized and at some it's an amazing thing when you think about this symptom which is a.

A loss of muscle tone in response to an emotional stimulus you'd think.

Either you have it or or you don't but what we find is that patients who ultimately are successfully diagnosed with narcolepsy when asked about cataplexy in terms that they understand like.

Your knees ever buckle, when you hear a joke does your two year cheeks ever Sag when you're feeling emotion will say Oh, yes, that's been true for years and when asked did you ever mentioned that to your doctor. The responses often I Didnt mentioned, that's my Doctor. It's just that weird thing that always happens to me so.

Long answer, but it it's unclear as to whether there are large growth group of patients that just don't experience cataplexy at all or whether its cataplexy that hasn't yet been.

Ben noticed and pointed out.

Bruce C. Cozadd: On 458, we're so excited to move this program forward but recognize it is a program still in R&D. We've still got work to do to make sure we're ready to go with a launch, with a robust, High Quality Reliable Manufacturing Process. We need to make sure that we uh... uh... do a nice job executing on the clinical protocol that I think Jazz, COG, and FDA put in place so nicely. And so, you know, I don't assess the technical risk as high, but there's always risk until On timing, you know, we've said that we could complete enrollment toward the end of next year. If an interim analysis yields positive data, that could accelerate our timeline. But there are lots of pieces to our timeline of when we could submit, including CMC work as well, so I don't want to get too far ahead of ourselves here.

On for 58, we're so excited to move this program forward, but recognize it is a program in still in R&D.

We still got work to do to make sure.

We're ready to go with the launch with a you know a robust.

Hi, quality, a reliable manufacturing process.

We need to make sure that we I do a nice job executing on the clinical protocol that I think China.

Chaz Cog and FDA put in place snow so nicely.

And so.

You know I, we don't assessed the technical risk as high but there's always risk until you finish development.

On timing.

We have said that we think we could complete enrollment.

Toward the end of next year.

On the interim analysis yields positive data that could accelerate our timeline.

But there are lots of pieces to our timeline of when we could submit including a CMC work as well so I don't want to get too far.

Ahead of ourselves here, but anything we can do to make sure we bring a quality product to market as quickly as possible we will do.

Bruce C. Cozadd: But anything we can do to make sure we bring a quality product to market as quickly as possible, we will do, and I think we've got great partners in COG and FDA all working together for the benefit of these mostly kids with ALL who, unfortunately, from time to time, have not been able to get therapy. Thank you. Thank you. And our next question comes from the line of David Reisinger with Morgan Stanley. Your line is now open.

And I think we've got great partners and Corgan F.D.A., all working together for the benefit as these.

Largely kids with they all who have unfortunately from time to time not been able to get a therapy when they need it.

Thank you.

Thank you.

And our next question comes from the line of David Risinger with Morgan Stanley . Your line is now open.

Yes. Thank you so.

Bruce C. Cozadd: Yes, thank you. With respect to the NCCN guideline change for Vixios, that should potentially benefit Vixios. Could you talk about that in a little bit more depth and how significant of an inflection you think that will be for the commercial uptake of Vixios? Hi, this is Mike, and the removal of 7 plus 3... You know, secondary AML has been the standard of care for 40 years. To have that removed from the NCCN guidelines is pretty significant, so we remain the only recommended treatment in the guidelines for fit and over-shaped Related AML.

With respect to the NCCN guideline change or.

That that should potentially benefit vyxeos.

Could you talk about that on a little bit more depth and how significant of an inflection.

You think that will be for the commercial uptake of Vyxeos. Thank you.

Hi, This is Mike and I and the removal of seven plus three which.

Secondary AML husband standard of care for 40 years.

I have that removed from the NCCN guidelines is pretty significant.

Shall we remain are only recommended treatment in the guidelines for fit and over 60 that would be for treatment related am Alabama mill.

Mike: So we're very excited about the data. We are very prepared to take this with our expanded team. And as Dan spoke about... And what was the timing of that? We began the actual expansion of the team, or the NCCN. The NCCN change, the removal of 7 plus 3. Alan, do you know?

So we're very excited about it we think the data certainly proves that out so we are very prepared.

Take this with our expanded team.

And as Dan spoke about active community, where more and more outpatient treatment of them out of this happen.

And what was the timing of that.

We began the actual expansion of the team or the NCCN change.

The NCCN change the removal of seven plus three.

Alan Yes, I think it was in July , but we can get back them on that it was in the quarter.

Alan: Yeah, I think it was in July, but we can get back to them on that. Okay, thank you. Thank you, and our next question comes from the line of Jessica Fye with JP Morgan. Your line is now open. Hi, this is Yuko on a call for Jessica. Thank you for taking our questions. How should we think about the potential of Sanofi opportunity in Europe? Would you frame your expectations in light of the standard of care and competitive landscape there?

Okay. Thank you.

Thank you and our next question comes from the line of Jessica Fye with JP Morgan Your line is no.

Hi. This is you go on the call for Jessica. Thank you for taking my questions. How should we think about the potential Sanofi opportunity out would you frame expectations in light of the standard of care and competitive landscape there.

Yes, so weve.

Bruce C. Cozadd: Yeah, so we've, you know, we've said we think this is a very significant opportunity when you look at patients with excessive daytime sleepiness and narcolepsy, and the even broader population of patients with EDS in OSA, we know that, you know, based on our prior research, that there's a fair amount of dissatisfaction with available therapies and we think coming to market with a new agent, new mechanism of action, we think really compelling efficacy data gives patients another great option, uh... in terms of quantifying that you know we've certainly given a sense for the size of the patient population what percent of that population we think is is dissatisfied and we said that over time we think in the U.S. market alone this could be a five hundred million dollar product in the existing indications now remember we're going to explore solar amphetol in indications beyond EDS and narcolepsy and OSA and that doesn't account for an ex-U.S. opportunity and obviously we believe we're uh... you know only a couple months away from getting an approval to bring that uh... agent to the european market as well so you know a really big opportunity for us we're just at the starting line from a commercial perspective a couple months into a U.S. launch and preparing for an EU launch So we've got a lot of work ahead of us, but there really is a tremendous opportunity including helping OSA treaters better recognize EDS in their patients. We believe that you know somewhere on the order of 40% of OSA patients, uh... have uh... excessive daytime sleepiness despite compliant use of CPAP uh... we're not coming along with something that's intended to replace CPAP this is something you would use along with your CPAP uh... to address that daytime symptomatology uh... with the daytime agents, And, you know, I think as they better understand that need, as overtime patients get more educated to talk to their OSA treaters about their daytime functioning, we see a real opportunity to improve treatment rate in the OSA population.

He said we think this is a very significant opportunity when you look at patients with excessive daytime sleepiness narcolepsy.

And the even broader population of patients with DDS in Oh, a say.

We know that based on our prior research that there's a fair amount of dissatisfaction with.

Available therapies, and we think.

Coming to market with a new agent new mechanism of action.

We think really compelling efficacy data.

Gives patients a another great option.

In terms of quantifying that we've certainly given a sense for the size of the patient population what percent of that population. We think is just satisfied and we said that over time, we think in the U.S. market alone this could be a $500 million product in the existing indications.

Now remember, we're going to explore sole ramp a tall in indications beyond Aesynt narcolepsy, you know assai and that doesn't account for an ex us opportunity and obviously, we believe were.

The only a couple of months away from getting an approval to bring that age into the European market as well so.

A really big opportunity for us we're just at the starting line from a commercial perspective, a couple months into U.S. launch and preparing for any you launch.

So we've got a lot of work ahead of us, but they're really as a tremendous opportunity.

Including helping Oh, let's say treaters better recognize mds in their patients we believe that somewhere on the order a 40% Oh, let's say patients.

Have a excessive daytime sleepiness, despite compliant use of see path.

We're not coming along with something that's intended to replace the path. This is something you would use along with receive path.

To address that daytime symptomatology.

With the daytime agents.

And.

I think as they better understand that need as overtime patients get more educated to talk to their own say treaters about their daytime functioning we see a real opportunity to improve treatment rate in the Oh, let's say population Bruce I'd also add to that I mean, I think our non branded campaign around raising the aware.

Bruce C. Cozadd: Bruce, I'd also add to that. I think our non-branded campaign around raising the awareness around EDS in OSA has really generated a lot of traffic, and we're very, As noted, we had 100 peer-to-peer, and 100 plus peer-to-peer programs in Q3, and that will certainly increase in Q4. Thank you. Thank you. And our next question comes from the line of Annabel Samimy with Stiefel. Your line is now open. Hi, this is Nick Rubino on behalf of Annabel.

Ornish around Mds say different kind of tired dot com has really generated a lot of track and we're very pleased about that occasional efforts continue Bruce noted we had 100.

Here.

Just a pair of programs in Q3 that will.

Certainly increase in Q4, then on two next year, we're excited about it.

Thank you.

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

Hi, This is Nick are being on Fran Bell, Thanks for taking my questions.

Bruce C. Cozadd: Thanks for taking our questions. How should we think about Sanosi's sampling and net pricing dynamics in early launch? And then maybe just some color on how we should think about IP and patent life for Sanosi. Thanks. So on your first question, how should you think about sampling and net pricing early in launch?

How should we think about Sanofi sampling and net pricing dynamics in the early launch and then maybe just some color on how we should think about IP and patent my personal see thanks.

So.

On your first question, how should do you think about sampling and a net pricing or early in launch.

Bruce C. Cozadd: You know, as we came into the launch and came into this year, we gave guidance on the revenue side of minimal revenues for, you know, sort of the second half of 2019. And we did that in large part because there was a very high gross-to-net adjustment early in launch. I mentioned that, you know, a number of patients are taking advantage of some of our programs to ensure they can get access to the drug with very reasonable out-of-pocket costs. We think that's a cost worth bearing to give people good trial and experience with the drug, both patients and through them, the prescribers, for them to get early clinical experience.

You know as we as we came into launch and came into this year, we gave guidance on the revenue side of minimal revenues.

For you know sort of the second half of 2019, and and we did that a large part because there is a very high gross to net.

Adjustment early in launch I I mentioned that.

You know a number of patients are taking advantage of some of our programs to ensure they can get access to the drug.

With a very reasonable out of pocket costs, we think thats a cost worth bearing to give people good trial and experience.

With the drug most patients and through patients the prescribers for them to get.

Early clinical experience. So we'll continue that will give you a different guidance as we move into next year.

Bruce C. Cozadd: So, you know, we'll continue that. We'll give you different guidance as we move into next year, but we think that's the right way to get started with this important new drug. And Kathy, can you take the IP patent side of sole re-inflammation? Yeah, it's a long patent life.

We think thats the right way to get started with this important new drugs and Kathy can you take the IP patent side of a us Orient football.

We can get.

Yes, it's long live patent life will come back you with exact date and Eminem.

Kathy Luttrell: We'll come back to you with the exact date. Alright, thank you. Operator, this will be the last question. No problem. And our last question does come from the line of Balaji Prasad with Barclays. Your line is now open.

All right. Thank you.

And operator this will be the last question coming out okay.

No problem.

And our last question does come from the line of my Lochee precise with Barclays. Your line is now open.

Bruce C. Cozadd: Hi, thank you. Good evening, and thanks for squeezing me in. Most of my questions have been answered. There are probably a couple of clarification questions.

Hi, Thank you good evening and thanks for squeezing me in most of my questions on the announcement a couple of.

Probably classification Cushe Swanton JCB create fly you said you plan to stop fees to be 2020 is it possible to provide any specific timelines smoke is more towards each one of which two andy fits to our they need to getting steps need to complete before then.

Rob: One on JZP385, you said you plan to start Phase 2B in 2020. Is it possible to provide any specific timelines? Is it more towards H1 or H2? And if H2, are there any other gating steps you need to complete before then? Yeah, Rob, you want to take that one?

Yeah, Rob you want to take that one.

I would anticipate it'd be more likely age to it as we mentioned.

Rob: I'd anticipate it would be more likely H2, and as we mentioned earlier in the call, we are finalizing a formulation that would be more appropriate for commercialization to be used in that 2B study. Thank you. Maybe if we could just squeeze in a question on Wixios. You mentioned that you expanded the team this quarter. Did you also imply that this was a cause for the growth, or is it going to be incremental from here on? Yeah, so we wanted to broaden our reach to make sure we had good coverage in the academic medical centers but also get out to the broader community providers.

In our earlier in the call. We are finalizing a formulation that would be more appropriate for commercialization to be used in that to be steady.

Thank you.

Maybe just quick question on weeks Hills, you mentioned that expanded the team this quarter.

Did you also light because it was close for the growth or is it going to be coming from me on.

Yes, so we wanted to broaden our reach to make sure. We had good coverage in the academic medical centers, but also get out to the broader.

Community Treaters, that's something I think we signaled even coming out of our second quarter call happy to say, we implemented a fairly rapid expansion of our team I got them trained up and they are out there out in the field, but they got out in the field as of October Onest. So no impact got a ton the third quarter, we'll see that going forward.

Bruce C. Cozadd: That's something I think we signaled even coming out of our second quarter call. I'm happy to say we implemented a fairly rapid expansion of our team, got them trained up, and they're out in the field. But they got out in the field as of October 1st, so they had no impact on the third quarter.

Bruce C. Cozadd: We'll see that going forward. Fantastic. That's really helpful.

Fantastic that's helpful. Thank you.

Bruce C. Cozadd: Thank you. Thank you. And that does include today's question and answer session.

Thank you and that does conclude today's question and answer session I would now like to turn the call back to Kathy Littrell for any further in March and Kathy Mabe. Thank you happy maybe before you go I just I just want to wrap up by.

Bruce C. Cozadd: I would now like to turn the call back to Kathy Luttrell for any further remarks. And, Kathy, maybe before you go, I just want to wrap up by thanking our teams at all our global sites and in the field for, you know, what was a pretty action-packed and successful quarter, really across our commercial launches, our existing products, and our R&D programs. We're not done. We've got a lot yet to accomplish this year.

Thank and our teams around all our global sites in the field for what was a pretty action packed and successful quarter.

Really across our commercial launches our existing products R&D programs.

We're not done we've got a lot you have to accomplish this year, but I really want to thank our employees around the world for just a really great job.

Kathy Luttrell: But I really want to thank our employees around the world for just a really great job. And I'll just follow up with one detail regarding exclusivity around CENOSI. We do have meaningful exclusivity, and that's patent protection through 2027 with the potential for a patent term extension.

I'll just follow up with the one detail to the question regarding exclusivity around.

We do have meaningful exclusivity and that patent protection through 2027 with the potential for patent term extension after approval.

Unknown Executive: And so, thank you all very much for joining us today. We will be participating in the upcoming conferences, the Piper Jaffray and the Evercore Healthcare Conferences, and hope to see many of you there. This now will end our conference call. Thank you for participating. You may now disconnect.

And so thank you all very much for joining us today, we will be participating in the upcoming Jefferies.

Conference the Piper Jaffrey, Andy Evercore health care comprehensive and hope to see many of you there is now well and our call.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.