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Item 1. Business

2025-02-26 compared with 2024-02-28 · 322 added, 353 removed, 726 unchanged (48% of the section changed)

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Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience.

Our strategy for growth is rooted in executing commercial launches and ongoing commercialization initiatives;

advancing robust research and development, or R&D, programs and delivering impactful clinical results;

effectively deploying capital to strengthen the prospects of achieving our short- and long-term goals through strategic corporate development;

and delivering strong financial performance.

Our strategy for growth is rooted in executing commercial launches and ongoing commercialization initiatives, advancing robust R&D programs and delivering impactful clinical results, effectively deploying capital to strengthen the prospects of achieving our short- and long-term goals through strategic corporate development, and delivering strong financial performance.

We focus on patient populations with high unmet needs.

We identify and develop differentiated therapies for these patients that we expect will be long-lived assets and that we can support with an efficient commercialization model.

We seek to identify and develop differentiated therapies for these patients that we expect will be long-lived assets and that we can support with an efficient commercialization model.

In addition, we leverage our efficient, scalable operating model and integrated capabilities across our global infrastructure to effectively reach patients around the world.

In January 2022, we announced our Vision 2025, which aims to deliver sustainable growth and enhanced value, driving our continued transformation to an innovative, high-growth global pharmaceutical leader.

The three core components of our Vision 2025 focus on commercial execution, pipeline productivity and operational excellence.

Our lead marketed products, listed below, are approved in countries around the world to improve patient care.

• Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution , a product approved by the U.S.

Food and Drug Administration, or FDA, in July 2020 and launched in the U.S.

in November 2020 for the treatment of cataplexy or excessive daytime sleepiness, or EDS, in patients seven years of age and older with narcolepsy, and also approved by FDA in August 2021 for the treatment of idiopathic hypersomnia, or IH, in adults and launched in the U.S.

• Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution , a product approved by FDA in July 2020, and launched in the U.S.

in November 2020 for the treatment of cataplexy or EDS in patients seven years of age and older with narcolepsy, and also approved by FDA in August 2021 for the treatment of IH in adults and launched in the U.S.

in November 2021.

Xywav contains 92% less sodium than Xyrem®.

• Xyrem (sodium oxybate) oral solution , a product approved by FDA and distributed in the U.S.

for the treatment of cataplexy or EDS in patients seven years of age or older with narcolepsy;

Jazz also markets Xyrem in Canada for the treatment of cataplexy in patients with narcolepsy.

Xyrem is also approved and distributed in the European Union, or EU (EU market authorizations include Northern Ireland), Great Britain and other markets through a licensing agreement;

Xywav is also approved in Canada for the treatment of cataplexy in patients with narcolepsy.

• Epidiolex® (cannabidiol) oral solution , a product approved by FDA and launched in the U.S.

in 2018 by GW Pharmaceuticals plc, or GW, and currently indicated for the treatment of seizures associated with Lennox-Gastaut syndrome, or LGS, Dravet syndrome, or DS, or tuberous sclerosis complex, or TSC, in patients one year of age or older;

in the EU and Great Britain (where it is marketed as Epidyolex®) and other markets listed in the table below, it is approved for adjunctive treatment of seizures associated with LGS or DS, in conjunction with clobazam (EU and Great Britain only), in patients 2 years of age and older and for adjunctive treatment of seizures associated with TSC in patients 2 years of age and older.

in 2018 by GW and currently indicated for the treatment of seizures associated with LGS, DS, or TSC in patients one year of age or older;

in the EU and Great Britain (where it is marketed as Epidyolex®) and other markets, it is approved for adjunctive treatment of seizures associated with LGS or DS, in conjunction with clobazam (EU and Great Britain only), in patients 2 years of age and older and for adjunctive treatment of seizures associated with TSC in patients 2 years of age and older.

• Rylaze® (asparaginase erwinia chrysanthemi (recombinant)-rywn) , a product approved by FDA in June 2021 and launched in the U.S.

in July 2021 for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma in adults and pediatric patients aged one month or older who have developed hypersensitivity to E.

in July 2021 for use as a component of a multi-agent chemotherapeutic regimen for the treatment of ALL or LBL in adults and pediatric patients aged one month or older who have developed hypersensitivity to E.

coli -derived asparaginase.

In September 2023, the European Commission, or EC, granted marketing authorization for this therapy under the trade name Enrylaze;

In September 2023, the European Commission granted marketing authorization under the trade name Enrylaze.

This therapy is also approved in markets including Great Britain, Canada and Switzerland.

• Zepzelca® (lurbinectedin) , a product approved by FDA in June 2020 under FDA's accelerated approval pathway and launched in the U.S.

in July 2020 for the treatment of adult patients with metastatic small cell lung cancer, or SCLC, with disease progression on or after platinum-based chemotherapy;

in July 2020 for the treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy;

in Canada, Zepzelca received conditional approval in September 2021 for the treatment of adults with Stage III or metastatic SCLC, who have progressed on or after platinum-containing therapy.

• Ziihera® (zanidatamab-hrii) , a product approved by FDA in November 2024 under FDA’s accelerated approval pathway and launched in the U.S.

in December 2024 for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) BTC, as detected by an FDA-approved test.

In 2024, consistent with our strategy, we continued to focus on research and development activities within our neuroscience and oncology therapeutic areas.

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Our Sleep Products .

We are the global leader in the development and commercialization of oxybate therapy for patients with sleep disorders.

Xyrem was approved by FDA in 2002 for treating EDS and cataplexy in narcolepsy.

We are the leader in the development and commercialization of oxybate therapy for patients with sleep disorders.

Xyrem was approved by FDA in 2002, and is indicated for treating cataplexy and EDS in patients seven years of age or older with narcolepsy.

In 2020, we received FDA approval for Xywav for the treatment of cataplexy or EDS in patients seven years of age and older with narcolepsy.

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Xywav has become a standard of care for patients with narcolepsy and IH.

In July 2020, FDA approved Xywav for the treatment of cataplexy and EDS in patients with narcolepsy.

In July 2020, FDA approved Xywav for the treatment of cataplexy and EDS in patients seven years of age and older with narcolepsy.

Narcolepsy is a chronic, debilitating neurological disorder characterized by EDS and the inability to regulate sleep-wake cycles normally.

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Narcolepsy may affect many areas of life, including limiting a patient’s education and employment opportunities, and may lead to difficulties at work, school, or in daily life activities like driving, operating machinery or caring for children.

Patients with narcolepsy may also suffer from significant medical comorbidities, including cardiac disorders, depression, suicide risk, anxiety, diseases of the digestive system and respiratory diseases.

Patients with narcolepsy may also suffer from significant medical comorbidities in both adult and pediatric populations, including increased psychiatric comorbidity (including anxiety disorders and mood disorders), intentional self-injury, attempted suicide, suicide-related mortality, other sleep disorders (such as periodic limb movement disorder), cardiovascular disorders (such as hypertension, coronary atherosclerosis, acute myocardial infarction, and congestive heart failure), and metabolic disorders (such as obesity, metabolic syndrome and diabetes).

Cataplexy, the sudden loss of muscle tone with retained consciousness, can be one of the most debilitating symptoms of narcolepsy.

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Therefore, we believe that reducing sodium intake compared to currently-marketed high-sodium oxybate products by 92% each day is a significant advancement for these patients.

The 92% reduction of sodium translates into a reduction of approximately 1,000 to 1,500 milligrams per day for a patient prescribed Xyrem, depending on the dose.

The 92% reduction of sodium translates into a reduction of approximately 1,000 to 1,500 milligrams per day for a patient prescribed high-sodium oxybate, depending on the dose.

Our commercial efforts are focused on educating patients and physicians about the lifelong impact of high sodium intake, and how the use of Xywav enables them to address what is a modifiable risk factor.

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We view the adoption of Xywav in narcolepsy as a positive indication that physicians and patients appreciate the benefits of a low-sodium oxybate option.

In June 2021, FDA recognized seven years of Orphan Drug Exclusivity, or ODE, for Xywav in narcolepsy through July 21, 2027.

Nevertheless, Lumryz, a fixed-dose, high-sodium oxybate, was approved by FDA on May 1, 2023 for the treatment of cataplexy or EDS in adults with narcolepsy.

In June 2021, FDA recognized seven years of ODE for Xywav in narcolepsy through July 21, 2027 (which was subsequently extended to January 21, 2028).

Nevertheless, Lumryz, a fixed-dose, high-sodium oxybate, was approved by FDA on May 1, 2023 for the treatment of cataplexy or EDS in adults with narcolepsy and was launched in the U.S.

market in June 2023.

FDA continues to recognize seven years of ODE for Xywav in narcolepsy.

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have been diagnosed with IH and are actively seeking healthcare.

We have agreements in place for Xywav with all three major pharmacy benefit managers, or PBMs, in the U.S.

We have agreements in place for Xywav with all three major PBMs in the U.S.

To date, we have entered into agreements with various entities and have achieved benefit coverage for Xywav in both narcolepsy and IH indications for approximately 90% of commercial lives.

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Xyrem was approved in the U.S.

for the treatment of cataplexy in adult patients with narcolepsy in 2002 and was approved for treatment of EDS in adult patients with narcolepsy in 2005.

for the treatment of cataplexy in patients with narcolepsy in 2002 and was approved for treatment of EDS in patients with narcolepsy in 2005.

In October 2018, Xyrem was also approved in the U.S.

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Our marketing, sales and distribution of Xywav and Xyrem in the U.S.

are subject to a risk evaluation and mitigation strategy, or REMS, which is required by FDA to mitigate the risks of serious adverse outcomes resulting from inappropriate prescribing, abuse, misuse and diversion of Xywav and Xyrem.

are subject to a REMS, which is required by FDA to mitigate the risks of serious adverse outcomes resulting from inappropriate prescribing, abuse, misuse and diversion of Xywav and Xyrem.

The Xywav and Xyrem REMS has the same requirements for both products.

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The central pharmacy ships the product directly to the patient (or caregiver) by a courier service.

We have had exclusive agreements with Express Scripts Specialty Distribution Services, Inc., or ESSDS, the central pharmacy for Xywav and Xyrem, to distribute Xywav and Xyrem in the U.S.

and provide patient support services related to Xyrem since 2002.

In December 2022, we entered into new agreements with ESSDS with a two-year term.

Since 2002, we have had exclusive agreements with ESSDS, the central pharmacy for Xywav and Xyrem, to distribute Xywav and Xyrem in the U.S.

and provide patient support services related to Xyrem.

In December 2022, we entered into new agreements with ESSDS with a two-year term and our ability to extend the term for an additional year.

Our current agreements with ESSDS, which expire on December 31, 2025, may be terminated by either party at any time without cause on 180 days’ prior written notice to the other party.

We acquired Epidiolex (Epidyolex outside the U.S.) in May 2021 as part of our acquisition of GW, which we refer to as the GW acquisition, which expanded our growing neuroscience business with a global, high-growth childhood-onset epilepsy franchise.

We acquired Epidiolex (Epidyolex outside the U.S.) in May 2021 as part of our GW Acquisition, which expanded our growing neuroscience business with a global, high-growth childhood-onset epilepsy franchise.

Epidiolex was approved in the U.S.

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FDA also approved the expansion of the other approved indications, LGS and DS, to patients one year of age and older.

The rolling European launch of Epidyolex is also underway following EC approval in September 2019 for use as adjunctive therapy of seizures associated with LGS or DS, in conjunction with clobazam, for patients two years of age and older.

In September 2019, the EC granted marketing authorization under the trade name Epidyolex for use as adjunctive therapy of seizures associated with LGS or DS, in conjunction with clobazam, for patients two years of age and older.

Epidyolex is now launched in all five key European markets:

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Epidyolex was also approved for adjunctive therapy in seizures associated with TSC for patients 2 years of age and older in the EU in April 2021 and Great Britain in August 2021, and is approved for this indication in other markets.

Outside the U.S.

and Europe, Epidiolex/Epidyolex is approved in Israel, Canada, Australia and New Zealand.

Epidiolex/Epidyolex is also approved in markets including Switzerland, Israel, Canada, and Australia.

See “Research and Development” below for a discussion of clinical development activities for Epidiolex.

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Net product sales of Epidiolex/Epidyolex in 2024 were $972.4 million , w hich represented 25% of our total net product sales for the year.

Rylaze was approved by FDA in June 2021 under the Real-Time Oncology Review, or RTOR, program, and was launched in the U.S.

in July 2021, for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute

lymphoblastic leukemia, or ALL, and lymphoblastic lymphoma, or LBL, in pediatric and adult patients one month and older who have developed hypersensitivity to E.

Rylaze was approved by FDA in June 2021 under the RTOR program, and was launched in the U.S.

in July 2021, for use as a component of a multi-agent chemotherapeutic regimen for the treatment of ALL, and LBL, in pediatric

and adult patients one month and older who have developed hypersensitivity to E.

coli-derived asparaginase.

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See “Research and Development” below for a discussion of clinical development activities for Rylaze.

The initial approved recommended dosage of Rylaze was for an intramuscular, or IM, administration of 25 mg/m 2 every 48 hours.

In November 2022, FDA approved a supplemental Biologics License Application, or sBLA, for a Monday/Wednesday/Friday 25/25/50 mg/m 2 IM dosing schedule.

In April 2022, we submitted a separate sBLA for intravenous, or IV, administration.

In February 2023, we received a complete response letter from FDA requesting additional clinical data on the IV administration of Rylaze.

There is no impact on the approved product labeling for Rylaze IM administration.

In September 2023, the EC granted marketing authorization for JZP458 (Rylaze) under the trade name Enrylaze and we have initiated a rolling launch in Europe.

The initial approved recommended dosage of Rylaze was for an IM administration of 25 mg/m 2 every 48 hours.

In November 2022, FDA approved an sBLA, for a Monday/Wednesday/Friday 25/25/50 mg/m 2 IM dosing schedule.

In September 2023, the EC granted marketing authorization for JZP458 (Rylaze) under the trade name Enrylaze.

Enrylaze was approved in Great Britain in January 2024, and is approved in other markets.

In 2024, net product sales of Rylaze were $410.8 million, which represented 11% of our total net product sales for the year.

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Our exclusive U.S.

development and commercialization rights to Zepzelca were acquired through an exclusive license agreement we entered into with Pharma Mar, S.A., or PharmaMar, in December 2019.

development and commercialization rights to Zepzelca were acquired through an exclusive license agreement we entered into with PharmaMar in December 2019.

In October 2020, we entered into an amendment to the license agreement with PharmaMar to expand our exclusive license to include rights to develop and commercialize Zepzelca in Canada.

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Zepzelca was granted orphan drug designation for adults with metastatic SCLC with disease progression on or after platinum-based chemotherapy by FDA in August 2018.

In December 2019, PharmaMar submitted a New Drug Application, or NDA, to FDA for accelerated approval of Zepzelca for relapsed SCLC based on data from a Phase 2 trial, and in February 2020, FDA accepted the NDA for filing with priority review.

In December 2019, PharmaMar submitted an NDA, to FDA for accelerated approval of Zepzelca for relapsed SCLC based on data from a Phase 2 trial, and in February 2020, FDA accepted the NDA for filing with priority review.

In June 2020, FDA granted accelerated approval of Zepzelca for the treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy.

Zepzelca is approved based on response rate and duration of response.

In collaboration with F.

Hoffmann-La Roche Ltd, or Roche, we have an ongoing Phase 3 pivotal clinical trial in first-line extensive stage SCLC of Zepzelca in combination with Tecentriq® (atezolizumab).

In collaboration with Roche, we have an ongoing Phase 3 pivotal clinical trial for Zepzelca for use as maintenance therapy in first-line extensive-stage SCLC in combination with Tecentriq® (atezolizumab) following induction therapy with carboplatin, etoposide and Tecentriq.

In October 2024, we announced positive top-line results from the trial showing a statistically significant and clinically meaningful benefit for Zepzelca and atezolizumab in combination in the first-line maintenance setting.

We plan to submit a sNDA in the first half of 2025 to support approval of this combination in the first-line maintenance setting.

In addition, our licensor PharmaMar is conducting a confirmatory trial in second-line SCLC.

This is a three-arm trial comparing Zepzelca as either monotherapy or in combination with irinotecan to investigator's choice of irinotecan or topotecan.

Data from either the first-line trial of Zepzelca in combination with Tecentriq or the PharmaMar trial could serve to confirm clinical benefit of Zepzelca and support full approval in the U.S.

Data from either the first-line maintenance trial of Zepzelca in combination with Tecentriq or the PharmaMar trial could serve to confirm clinical benefit of Zepzelca and support full approval in the U.S.

See “Research and Development” below for a discussion of clinical development activities for Zepzelca.

In 2024, net product sales of Zepzelca were $320.3 million, which represented 8% of our total net product sales for the year.

We acquired our exclusive development and commercialization rights to Ziihera in 2022 through a licensing agreement with a subsidiary of Zymeworks providing development and commercialization rights to zanidatamab across all indications in the U.S., Europe, Japan and all other territories except for those Asia/Pacific territories previously licensed by Zymeworks.

The term of the license agreement extends on a licensed product-by-licensed product and country-by-country basis until the expiration of the royalty term for such licensed product in such country.

We have the right to terminate the license agreement at will upon a specified notice period, and either party can terminate the license agreement for the other party’s uncured material breach or bankruptcy.

Ziihera is a bispecific HER2-directed antibody that binds to two extracellular sites on HER2.

Binding of zanidatamab-hrii with HER2 results in internalization leading to a reduction of the receptor on the tumor cell surface.

In the U.S., Ziihera is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) BTC, as detected by an FDA-approved test.

Ziihera was launched in December 2024.

In 2024, net product sales of Ziihera were $1.1 million, which represented less than 1% of our total net product sales for the year.

Revenue Diversification

As part of our objective to build a durable, growing commercial portfolio and reduce business risk by diversifying our revenue sources, we have been actively seeking to expand our commercial portfolio thorough a combination of launching internally developed therapies and commercial assets or investigational therapies acquired through corporate development.

In 2018, 74% of total revenue was generated by one product, Xyrem.

For the year ended December 31, 2023, 50% of total revenue was generated outside of our Sleep products, Xywav and Xyrem, plus high-sodium oxybate AG royalty revenue.

Our marketed products, listed below, are approved in countries around the world to improve patient care.

In 2020, 74% of total revenue was generated by one product, the high-sodium oxybate Xyrem.

For the year ended December 31, 2024, 11% of total revenue was generated by Xyrem plus high-sodium oxybate AG royalty revenue.

Our lead marketed products, listed below, are approved in countries around the world to improve patient care.

Product Indications Initial Approval Date Markets

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May 2023 Canada

Xyrem® (sodium oxybate) Treatment of cataplexy or EDS in patients seven years of age and older with narcolepsy.

July 2002 U.S.

Treatment of cataplexy in patients with narcolepsy.

August 2005 Canada

Treatment of narcolepsy with cataplexy in adult patients, adolescents and children from age of 7 years.

October 2005 EU, Great Britain, other markets (through licensing agreement)

Epidiolex® (cannabidiol) Treatment of seizures associated with LGS, DS, or TSC, in patients 1 year of age and older.

June 2018 U.S.

Epidyolex® (cannabidiol) For adjunctive therapy of seizures associated with LGS or DS, in conjunction with clobazam, for patients 2 years of age and older.* September 2019 EU, Great Britain, EEA**, Israel, Switzerland, Australia and New Zealand

Epidyolex® (cannabidiol) For adjunctive therapy of seizures associated with LGS or DS, in conjunction with clobazam, for patients 2 years of age and older.

September 2019 EU, Great Britain, EEA, Israel, Switzerland, Australia, other markets

For adjunctive therapy of seizures associated with TSC for patients 2 years of age and older.

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coli-derived asparaginase.

September 2023 EU, Great Britain

September 2023 EU, Great Britain, Switzerland, other markets

Zepzelca® (lurbinectedin) Treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy.

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September 2021 Canada (licensed from PharmaMar) 3

Defitelio® (defibrotide) Treatment of severe hepatic veno-occlusive disease, or VOD, also known as sinusoidal obstruction syndrome, or SOS, following hematopoietic stem cell transplantation, or HSCT, therapy.

October 2013 EU, Great Britain, EEA**, Switzerland, Israel, Australia, South Korea, Saudi Arabia

Defitelio® (defibrotide sodium) Treatment of adult and pediatric patients with hepatic VOD, also known as SOS, with renal or pulmonary dysfunction following HSCT.

March 2016 U.S.

Defitelio® (defibrotide sodium) Treatment of severe hepatic VOD, also known as SOS, following HSCT therapy.

July 2017 Canada, Brazil

Defitelio® (defibrotide) Treatment of hepatic SOS (hepatic VOD).

June 2019 Japan

Vyxeos® (daunorubicin and cytarabine) liposome for injection Treatment of newly-diagnosed therapy-related acute myeloid leukemia, or t-AML, or AML with myelodysplasia-related changes, or AML-MRC, in adults and pediatric patients one year and older.

August 2017 U.S.

Vyxeos® liposomal

44 mg/100 mg powder for concentrate for solution for infusion Treatment of adults with newly-diagnosed t-AML or AML-MRC.

August 2018 EU, Great Britain, Switzerland, Israel, Australia, South Korea, Saudi Arabia

Vyxeos® Daunorubicin and cytarabine liposome for injection Powder, 44 mg daunorubicin and 100 mg cytarabine per vial, IV infusion Treatment of adults with newly diagnosed therapy-related t-AML or AML with AML-MRC.

April 2021 Canada

Ziihera® (zanidatamab-hrii) Treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) BTC, as detected by an FDA-approved test.

November 2024 U.S.

(licensed from Zymeworks) 2

1 The clobazam restriction limited to EU and Great Britain

**European Economic Area

2 Accelerated approval received from FDA

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Research and Development Progress

A key aspect of our strategy is our continued investment in expanding our research and development organization and initiatives.

We actively explore new options for patients including novel compounds, small molecule advancements, biologics and innovative delivery technologies.

We are focused on research and development activities within our oncology and neuroscience therapeutic areas and exploring and potentially investing in adjacent therapeutic areas.

Our research and development activities encompass all stages of development and currently include clinical testing of new product candidates and activities related to clinical improvements of, or additional indications or new clinical data for, our existing marketed products.

We also have active preclinical programs for novel therapies, including neuroscience and precision medicines in oncology.

We are increasingly leveraging our growing internal research and development function, and we have

also entered into collaborations with third parties for the research and development of innovative early-stage product candidates and have supported additional investigator-sponsored trials, or ISTs, that are anticipated to generate additional data related to our products.

We are increasingly leveraging our growing internal research and development function, and we have also entered into collaborations with third parties for the research and development of innovative early-stage product candidates and have supported additional investigator-sponsored trials that are anticipated to generate additional data related to our products.

We also seek out investment opportunities in support of the development of early- and mid-stage technologies in our therapeutic areas and adjacencies.

We have a number of licensing and collaboration agreements with third parties, including biotechnology companies, academic institutions and research-based companies and institutions, related to preclinical and clinical research and development activities in hematology and precision oncology, as well as in neuroscience.

Zanidatamab .

We acquired our exclusive development and commercialization rights to Zanidatamab in 2022 through an exclusive licensing agreement with a subsidiary of Zymeworks Inc., or Zymeworks, providing development and commercialization rights to Zanidatamab across all indications in the U.S., Europe, Japan and all other territories except for those Asia/Pacific territories previously licensed by Zymeworks.

The term of the license agreement extends on a licensed product-by-licensed product and country-by-country basis until the expiration of the royalty term for such licensed product in such country.

We have the right to terminate the amended license agreement at will upon a specified notice period, and either party can terminate the amended license agreement for the other party’s uncured material breach or bankruptcy.

Zanidatamab is an investigational HER2-targeted bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding.

Zanidatamab is a HER2-targeted bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding.

Zanidatamab is currently being evaluated in multiple clinical trials as a treatment for patients with HER2-expressing cancers.

Following positive data from a pivotal Phase 2 clinical trial evaluating zanidatamab monotherapy in patients with previously treated advanced or metastatic HER2-amplified biliary tract cancers, or BTC, we initiated a rolling Biologics License Application, or BLA, submission for accelerated approval in second-line BTC.

In addition, we have an ongoing Phase 3 randomized clinical trial evaluating zanidatamab in combination with chemotherapy plus or minus tislelizumab as a first-line treatment for HER2-expressing gastroesophageal adenocarcinoma, or GEA, and an ongoing Phase 2 trial examining zanidatamab in combination with chemotherapy in first-line patients with HER2-expressing metastatic GEA.

In November 2024, we announced that zanidatamab had been approved by FDA for treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) BTC, as detected by an FDA-approved test.

We have an ongoing Phase 3 randomized clinical trial evaluating zanidatamab in combination with chemotherapy plus or minus tislelizumab as a first-line treatment for HER2-expressing GEA, an ongoing Phase 2 trial examining zanidatamab in combination with chemotherapy in first-line patients with HER2-expressing metastatic GEA and an ongoing Phase 3 trial examining zanidatamab in first-line patients with HER2-positive BTC.

There are also multiple ongoing clinical trials exploring zanidatamab in breast cancer and other HER2-expressing tumor types.

Our development plan for Zepzelca continues to progress.

In collaboration with Roche, we have an ongoing Phase 3 pivotal clinical trial in first-line extensive stage SCLC of Zepzelca in combination with Tecentriq ® (atezolizumab).

In collaboration with Roche, we have an ongoing Phase 3 pivotal clinical trial in use as maintenance therapy in first-line extensive-stage SCLC of Zepzelca in combination with Tecentriq ® (atezolizumab).

In addition, our licensor PharmaMar is conducting a confirmatory trial in second-line SCLC.

This is a three-arm trial comparing Zepzelca as either monotherapy or in combination with irinotecan to investigator's choice of irinotecan or topotecan.

Data from either the first-line trial of Zepzelca in combination with Tecentriq or the PharmaMar trial could serve to confirm clinical benefit of Zepzelca and support full approval in the U.S.

In 2023, we elected to close the Phase 2 basket trial evaluating Zepzelca as monotherapy in patients with select relapsed/refractory solid tumors based on limited response in three solid tumor cohorts.

We have an ongoing Phase 4 observational study to collect real world safety and outcome data in adult Zepzelca monotherapy patients with SCLC who progress on or after prior platinum-containing chemotherapy.

Vyxeos® (daunorubicin and cytarabine) liposome for injection is a product approved in the U.S., Canada, EU, Great Britain and other markets (marketed as Vyxeos® liposomal in the EU, Great Britain and other markets) for the treatment of adults with newly diagnosed t-AML or AML-MRC.

Our Vyxeos clinical development strategy is designed to target potential new patient segments across the AML landscape and to generate clinical data on Vyxeos when used in combination with other therapeutic agents.

JZP815 is a pan-RAF kinase inhibitor that targets specific components of the mitogen-activated protein kinase, or MAPK, pathway that, when activated by oncogenic mutations, can be a frequent driver of human cancer.

JZP815 is a pan-RAF kinase inhibitor that targets specific components of the MAPK pathway that, when activated by oncogenic mutations, can be a frequent driver of human cancer.

In October 2022, we enrolled our first patient in a Phase 1 study to investigate the safety, dosing, and initial antitumor activity of JZP815 in participants with advanced or metastatic solid tumors harboring alterations in the MAPK pathway.

JZP898 is a differentiated, conditionally-activated interferon alpha, or IFNα, INDUKINE™ molecule.

We acquired rights to JZP898 from Werewolf Therapeutics, Inc., or Werewolf, in 2022 under an exclusive, worldwide, royalty-bearing license to develop, manufacture and commercialize Werewolf's investigational WTX-613, now referred to as JZP898.

JZP898 is a differentiated, conditionally-activated IFNα INDUKINE™ molecule.

We acquired rights to JZP898 from Werewolf in 2022 under an exclusive, worldwide, royalty-bearing license to develop, manufacture and commercialize Werewolf's investigational WTX-613, now referred to as JZP898.

In November 2023, we enrolled our first patient in a Phase 1 study to investigate the safety, tolerability, pharmacokinetics, immunogenicity and preliminary antitumor activity of JZP898 both as a monotherapy and in combination with pembrolizumab in adults with advanced/metastatic solid tumors.

We have an ongoing Phase 3 trial of Epidyolex for LGS, DS and TSC in Japan.

Suvecaltamide (JZP385) .

Suvecaltamide (JZP385) is a highly selective modulator of T-type calcium channels currently in development for the potential treatment of essential tremor, or ET.

ET is the most common pathological movement disorder, and there have been no new approved therapies in more than 50 years.

We acquired suvecaltamide in our acquisition of Cavion, Inc., or Cavion, a clinical-stage biotechnology company, in August 2019.

We initiated a Phase 2b clinical trial of suvecaltamide in December 2021.

In this multicenter, double-blind, randomized, placebo-controlled trial, we are evaluating the safety and efficacy of suvecaltamide in the treatment of adults with moderate to severe ET.

The primary efficacy outcome measure is the change from baseline to Week 12 on the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) composite outcome score, which represents items from the TETRAS-Activities of Daily Living and TETRAS-Performance Subscale, and measures the functional impact due to tremor.

Additionally, in November 2022, we initiated a Phase 2 trial of suvecaltamide in patients with Parkinson's disease tremor.

JZP150 is a fatty acid amide hydrolase inhibitor program for the potential treatment of post-traumatic stress disorder, or PTSD, and associated symptoms.

We initiated a Phase 2 clinical trial of JZP150 for PTSD in December 2021.

In December 2023, we announced that this trial did not meet the primary endpoint in the treatment of adults with PTSD as measured by improvement in the Clinician Administered Post Traumatic Stress Disorder (PTSD) Scale (CAPS-5) Total Symptom Severity Score.

In August 2024, we announced top-line results from the trial.

The trial did not meet the primary efficacy endpoint of a pre-specified percentage change in indication-associated seizure frequency during the treatment period (up to 16 weeks) compared to baseline in Japanese pediatric patients;

however, numeric improvements were observed in the primary and several secondary endpoints.

No new safety signals were observed in the trial.

We are continuing to collect data in Japanese patients and plan to engage with regulatory authorities in Japan regarding a potential new drug application.

JZP441 is a potent, highly selective oral orexin-2 receptor agonist with potential application for the treatment of narcolepsy, IH and other sleep disorders.

In May 2022, we announced that we had entered into a licensing agreement with Sumitomo Pharma Co., Ltd, or Sumitomo, to acquire exclusive development and commercialization rights in the U.S., Europe and other territories for DSP-0187, now referred to as JZP441.

In May 2022, we announced that we had entered into a licensing agreement with Sumitomo to acquire exclusive development and commercialization rights in the U.S., Europe and other territories for DSP-0187, now referred to as JZP441.

Sumitomo initiated a Phase 1 trial in Japan in November 2021 to evaluate safety, tolerability and pharmacokinetics of JZP441 in healthy volunteers.

In November 2022, we initiated a Phase 1 development program to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of JZP441 in sleep-deprived healthy volunteers.

In November 2023, we announced that the study achieved proof of concept in healthy volunteers based on the Maintenance of Wakefulness Test and that the program is being paused as we analyze safety findings related to visual disturbances and cardiovascular effects;

In November 2022, we initiated a Phase 1 development

program to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of JZP441 in sleep-deprived healthy volunteers.

In November 2023, we announced that the study achieved proof of concept in healthy volunteers based on the Maintenance of Wakefulness Test and that the program was being paused as we analyzed safety findings related to visual disturbances and cardiovascular effects;

no liver toxicity signals were observed.

Following additional review of the trial findings and input from FDA, we plan to initiate a small Phase 1b trial of JZP441 in narcolepsy Type 1 patients in 2025.

We expect data from this trial will further our understanding of JZP441 and orexin-2 receptor agonism, providing learnings that could inform potential future development efforts.

We are also pursuing early-stage activities related to the development of JZP324, an extended-release low sodium oxybate formulation that we believe could provide a clinically meaningful option for patients with serious sleep disorders.

Through third parties, we are also pursuing oncology and neuroscience preclinical and clinical research and development activities under a number of licensing and collaboration agreements, including with:

• XL-protein GmbH, or XLp, for rights to use XLp’s PASylation ® technology to extend the plasma half-life of selected asparaginase product candidates;

• Redx Pharma plc, or Redx, for preclinical collaboration activities related to the Ras/Raf/MAP kinase pathway program that we purchased from Redx;

• XLp for rights to use XLp’s PASylation ® technology to extend the plasma half-life of selected asparaginase product candidates;

• Redx for preclinical collaboration activities related to the Ras/Raf/MAP kinase pathway program that we purchased from Redx;

• We are also evaluating the use of our CombiPlex delivery technology platform in a number of therapeutic formulations and combinations in oncology as part of our internal oncology research and development activities;

• Autifony Therapeutics Limited to collaborate on discovering and developing drug candidates targeting two different ion channel targets associated with neurological disorders.

• Autifony to collaborate on discovering and developing drug candidates targeting two different ion channel targets associated with neurological disorders.

Below is a summary of our key ongoing and planned development projects related to our products and pipeline and their corresponding current stages of development:

Product Candidates Description

Zanidatamab HER2-positive GEA (ongoing trial)

Zepzelca First-line extensive stage SCLC in combination with Tecentriq (collaboration with Roche) (ongoing trial)

Confirmatory Study (PharmaMar study) (ongoing trial)

Vyxeos AML or high-risk Myelodysplastic Syndrome, or MDS (AML18) (cooperative group studies) (ongoing trial)

Regulatory Review

Zanidatamab Second-line HER2-expressing BTC (under EMA review)

Zanidatamab First-line HER2-positive GEA (ongoing trial)

Zanidatamab First-line HER2-positive BTC (ongoing trial)

Zanidatamab Previously treated HER2-positive breast cancer in patients whose disease has progressed on previous T-DXd treatment (EmpowHER-BC-303) (ongoing trial)

Zepzelca First-line maintenance for extensive-stage SCLC in combination with Tecentriq (collaboration with Roche) (ongoing trial)

Confirmatory second-line trial (PharmaMar study) (ongoing trial)

Vyxeos AML or MDS (AML18) (cooperative group studies) (ongoing trial)

Newly diagnosed adults with standard- and high-risk AML (AML Study Group cooperative group study) (ongoing trial)

Newly diagnosed pediatric patients with AML (Children’s Oncology Group cooperative group study) (ongoing trial)

Pivotal Phase 2

Zanidatamab Previously treated, advanced HER2-expressing BTC (ongoing trial) (pivotal trial)

Newly diagnosed pediatric patients with AML (COG cooperative group study) (ongoing trial)

Zanidatamab HER2-expressing GEA, BTC or colorectal cancer in combination with standard first-line chemotherapy (ongoing trial)

Zanidatamab Basket trial including HER2-positive solid tumors (DiscovHER-Pan-206) (ongoing trial)

Vyxeos High-risk MDS (European Myelodysplastic Syndromes) (cooperative group study) (ongoing trial)

Newly diagnosed untreated patients with high-risk AML (cooperative group study) (planned trial)

Vyxeos + other approved therapies Relapsed/refractory, or R/R, AML or hypomethylating agent failure MDS (MD Anderson collaboration study) (ongoing trial)

Newly diagnosed untreated patients with intermediate- and high-risk AML (cooperative group study) (ongoing trial)

Vyxeos + other approved therapies R/R AML or hypomethylating agent failure MDS (MD Anderson collaboration study) (ongoing trial)

De novo or R/R AML (MD Anderson collaboration study) (ongoing trial)

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JZP815 Raf and Ras mutant tumors (acquired from Redx) (ongoing trial)

Zanidatamab Previously treated metastatic HER2-expressing cancers in combination with select antineoplastic therapies (ongoing trial)

JZP341 (long-acting Erwinia asparaginase)

Solid tumors (licensed from Ligand Pharmaceuticals Incorporated, or Ligand) (ongoing trial)

Zanidatamab Previously treated metastatic HER2-expressing cancers in combination with select antineoplastic therapies (cooperative group study) (ongoing trial)

JZP898 Conditionally-activated IFNα INDUKINE™ molecule in solid tumors (ongoing trial)

Vyxeos Low intensity dosing for higher risk MDS (MD Anderson collaboration study) (ongoing trial)

Undisclosed target Ras/Raf/MAP kinase pathway (collaboration with Redx)

KRAS inhibitor targets G12D selective and pan-KRAS molecules (acquired from Redx)

Undisclosed targets Oncology

Oncology exploratory activities

Hematology/oncology exploratory activities

Epidyolex LGS, TSC and DS (ongoing trial in Japan)

Suvecaltamide (JZP385)

ET (ongoing trial)

Suvecaltamide (JZP385)

Parkinson's disease tremor (ongoing trial)

JZP324 Oxybate extended-release formulation (planned trial)

JZP441* Potent, highly selective oral orexin-2 receptor agonist (paused)

Undisclosed cannabinoids Other neuroscience (ongoing trials)

JZP441* Potent, highly selective oral orexin-2 receptor agonist (ongoing trial)

Undisclosed targets Sleep

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We have direct Jazz commercial operations in the U.S., Europe, Australia and Canada and a network of commercial distributors that represent our commercial interests in other key markets across the globe.

In the U.S., our products are commercialized through a number of teams, including a team of experienced, trained sales professionals who provide education and promote Xywav, Xyrem, Epidiolex, Zepzelca, Rylaze, Vyxeos and Defitelio to healthcare providers in the appropriate specialties for each product, a team that interacts with payors and institutions to ensure access and coverage for the products, and a team that distributes the products throughout the U.S.

In the U.S., our products are commercialized through a number of teams, including a team of experienced, trained sales professionals who provide education and promote Xywav, Epidiolex, Zepzelca, Rylaze, Ziihera, Vyxeos and Defitelio to healthcare providers in the appropriate specialties for each product.

In addition, we have a team that interacts with payors and institutions to ensure access and coverage for the products, as well as Xyrem, and a team that distributes the products throughout the U.S.

healthcare system (wholesalers, pharmacies, hospitals, and community and academic institutions) and provides patient services.

In Canada and in approved markets in Europe where we commercialize Defitelio and Vyxeos, we have a field force of hematology sales specialists.

In Canada and in approved markets in Europe and Australia where we commercialize Defitelio and Vyxeos, we have a field force of hematology sales specialists.

In markets where these products either are not approved or are unable to be promoted under local regulation, we have medical affairs personnel responsible for responding to medical information requests and for providing information consistent with local treatment protocols with respect to such products.

In certain European markets, we have a sales team and a team of medical science liaisons supporting our rolling launch of Epidyolex.

In addition, we directly market Xyrem and Zepzelca in Canada.

In certain European markets and Australia, we have a sales team and a team of medical science liaisons supporting our commercialization of Epidyolex.

In addition, we directly market Xywav, Xyrem and Rylaze in Canada.

Other commercial activities include marketing related services, pricing and access, industry analytics and insights, distribution services and commercial support services.

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We intend to scale the size of our sales force as appropriate to effectively reach our target audience in the specialty markets in which we currently operate.

We promote Zepzelca, Rylaze, Vyxeos and Defitelio to many hematology and oncology specialists who operate in the same hospitals and outpatient clinical sites, and we believe that we benefit from operational synergies from this overlap.

We expect that the launch of Enrylaze in Europe will be executed primarily through our existing team.

We promote Zepzelca, Rylaze, Vyxeos, Defitelio and Ziihera to many hematology and oncology specialists who operate in the same hospitals and outpatient clinical sites, and we believe that we benefit from

operational synergies from this overlap.

Continued growth of our current marketed products and the launch of any future products may require a reevaluation of our field force and support organization in and outside the U.S.

Human Capital Management and Environment, Health and Safety

We are committed to creating a company where the culture embodies our corporate purpose to innovate to transform the lives of patients and reflects our key goals:

(1) be a great place to work and (2) live our core values of Integrity, Collaboration, Passion, Innovation, and Pursuit of Excellence.

High Performance Organization and Human Capital Management

We are committed to creating a high performing company where the culture embodies our corporate purpose to innovate to transform the lives of patients and reflects our key goals:

(1) be a purpose-driven, people-centric, and great place to work and (2) live our core values of Integrity, Collaboration, Passion, Innovation, and Pursuit of Excellence.

Employee Demographics .

As of December 31, 2024, Jazz employed approximately 2,800 people worldwide, of which approximately 50% were employed in the U.S.

and approximately 50% were employed outside the U.S.

primarily in the U.K., Ireland and across the EU.

and approximately 50% were employed outside the U.S., primarily in the U.K., Ireland and across the EU.

As an innovative biopharmaceutical company, we have over 740 employees — representing approximately 27% of our global workforce — supporting our research and development activities.

We consider our employee relations to be very good.

Diversity, Equity, Inclusion and Belonging.

We make diversity, equity, inclusion and belonging, or DEIB, a priority because it is a key to driving business performance, unlocking the potential of our people and living our core values.

We consider our employee relations to be good.

Company Culture .

We believe a culture rooted in purpose, centered on people, and focused on performance is key to unlocking our full potential and achieving sustainable success.

By prioritizing a people-centric and performance-based approach, we aim to create a workplace where purpose fuels passion, leading to innovative solutions and exceptional business outcomes.

We aim to create an environment where our employees live our core values to unlock the full potential of our people as a key to driving business performance.

We are committed to fostering an inclusive environment where all employees feel they belong, which in turn brings a variety of perspectives that drive innovation and business success.

We strive to create a workplace culture that fosters the ability of our employees to be their authentic selves and contribute boldly.

We aspire to have diversity through our entire workforce.

We seek to surround underrepresented groups with allies to enable all employees to thrive equitably.

Our board of directors and management team are committed to fostering DEIB in all parts of our business.

Our DEIB strategy includes:

(1) building a more diverse workforce in terms of gender identity, race, ethnicity and sexual orientation and that represent unique backgrounds, experiences, thoughts and talents;

(2) investing in talent development and driving equity;

and (3) and creating a culture of inclusion and belonging.

We believe an employee community that fosters diversity and inclusion leads to innovation and improved business performance.

We have created three Employee Resource Teams, or ConcERTos, and five Affinity Forums and provided a platform for broader company engagement and education.

Our three ConcERTos, “Community Beat,” “All Dimensions of Diversity” and “Inclusion for Innovation,” were established as broad self-led teams of employee volunteers with diverse backgrounds with the aim of connecting our employees, or Jazzicians, with similar visions and interests in an inclusive, welcoming, and collaborative setting.

The five Affinity Forums include, ¡HOLA Jazz!

(Hispanic Organization for Leadership Advancement), JazzSoul, JAWS (Jazz Association for Women Supporters), Jazz Pride and Pan-Asian and are places of connection and learning for members of these communities and their allies.

As of the end of 2023, 32% of our global workforce were active in at least one of these groups.

We have established aspirational goals related to the diversity of our workforce, including representation of women and people of color, particularly at the leadership level (i.e., employees at executive director and above).

In this regard, we have made some meaningful progress, as demonstrated by the following, as of December 31, 2023:

• 50% of our board of directors and 60% of our executive committee is diverse in terms of gender, ethnicity and sexual orientation.

Our belonging and inclusion strategy includes:

(1) cultivating a workforce that reflects unique backgrounds, experiences, and talents and represents the varied perspectives of the patients and customers we serve;

(2) investing in talent development and ensuring equal opportunities for all;

and (3) creating a culture of inclusion and belonging.

As of December 31, 2024,

• 50% of our board of directors and 56% of our executive committee is diverse in terms of gender, ethnicity and/or sexual orientation.

• Women represent 55% of our global workforce and 46% at the leadership level (employees at executive director and above).

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workforce and 20% at the leadership level.

While we are proud of what we have accomplished to date, we remain committed to our aspiration of providing a diverse, equitable and inclusive workplace that is supportive of all backgrounds, including among our broader leadership.

We believe an employee population that reflects the communities that we serve and a culture that fosters belonging and inclusion leads to innovation, employee engagement, and strong business performance.

We have created various employee resource groups with membership open to all employees consisting of three ConcERTos, and six Affinity Forums representing the wide variety of backgrounds of our employees and providing a platform for broader company engagement and education.

Our ConcERTos and Affinity Forums were established as broad self-led teams of employee volunteers with varied backgrounds and perspectives with the aim of connecting Jazz employees with similar visions and interests in inclusive, welcoming, and collaborative settings.

As of the end of 2024, 37% of our global workforce were active in at least one of these groups.

While we are proud of what we have accomplished to date, we remain committed to our aspiration of providing an inclusive and high-performing workplace that is supportive of all backgrounds, including among our broader leadership.

Employee Engagement .

We have a strong employee value proposition anchored in our shared commitment to our purpose to innovate to transform the lives of patients.

We are committed to ensuring that we create a rich culture that provides a great place to work for our employees through company-wide efforts to connect employees to our shared purpose and to create an environment where our people feel valued, respected, and able to contribute to their full potential.

We believe employee engagement and the power of our employee voices is foundational to strong performance.

We have transparent and regular communication channels with our employees consisting of many forms – including all employee meetings, regular communication messages from executive leadership, town halls, top leadership forums, pulse check feedback mechanisms and engagement surveys.

In 2023, to mark our 20-Year Anniversary we provided the opportunity for all employees to come together and reconnect to our Purpose and Values in a series of in-person and virtual events.

In advance of the events, a culture diagnostic was completed to help us understand what behaviors will help drive future business success across Jazz and informed a refresh of the behavioral descriptors that underpin the Jazz Values.

In total, 31 in-person and 11 virtual sessions across 9 global locations took place in the fourth quarter of 2023, with almost 2,000 employees taking part.

The goal of these events, in addition to other 20 th anniversary observances throughout the year, was to promote greater feelings of employee belonging and an increase in overall employee engagement, as well as help shift our culture to ensure sustained business success.

We have a strong employee value proposition anchored in our shared commitment to our purpose to innovate to transform the lives of patients and their families.

We believe employee engagement and the power of our employee voices is foundational to employee belonging and strong performance.

Our employee feedback surveys are designed to help us measure overall employee engagement as well as gather insights on other important areas of our employee experience, and we consistently achieve participation rates above 75%.

We consistently have high levels of engagement as measured by feelings of connection to our purpose, as well as Jazz being considered a good place to work by our employees.

Our surveys also provide important insight into the areas where we have opportunities to focus, such as decision-making, planning and prioritizing work, and creating a greater sense of belonging.

We consistently have high levels of engagement as measured by employees’ feelings of connection to our purpose, a sense of belonging, as well as Jazz being considered a good place to work by our employees.

We continue to focus on high-performance practices we have deemed critical, such as decision-making, planning and prioritizing work, speaking up and constructive challenge, accountability, and a growth mindset.

Our survey informs programs and activities aligned with achieving our corporate objectives and achieving our goal of evolving our operating culture for agility and scalability.

Our Community Beat ConcERTo is made up of employee volunteers and representatives that promote company culture and create a sense of belonging and camaraderie among our employees.

They foster programs and engagement activities on a local level to draw better connections to employees with the company strategy and business milestones, give back through community service, and promote different health and well-being initiatives.

Our Community Beat ConcERTo is made up of employee volunteer teams that promote company culture and create a sense of belonging and camaraderie among our employees.

They organize programs and engagement activities on a local level to connect employees with the company strategy and business goals, support local communities, and promote employee health

and well-being initiatives.

They play a pivotal role in fostering community within our working model by engaging remote employees and maximizing connection during times together at our sites and offices.

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In 2024, we continued to focus on developing the capabilities of our Global Leadership Team (Top 80 leaders) to build leadership excellence, strengthen relationships, and encourage cross functional collaboration in pursuit of our enterprise strategic goals.

Our focus in 2023 was on building critical mindsets and behaviors linked to a high-performance culture, e.g., how to create an environment where people feel able to constructively challenge one another.

Our management and leadership teams place significant focus and attention to diversity, capability development, and succession planning for critical roles.

Our focus in 2024 was on building people manager excellence and behaviors linked to a high-performance culture, e.g., how to create an environment where people feel able to constructively challenge one another.

Our management and leadership teams place significant focus and attention to capability development and succession planning for critical roles.

We regularly review talent development and succession plans for each of our functions to successfully maintain business operations and develop a pipeline of talent.

We have aspirational goals concerning employee retention, diversity, and talent development.

We provide our employees with what we believe to be market competitive and locally relevant compensation and benefits that support our overarching strategy to attract, retain and reward highly talented employees in an extremely competitive and dynamic industry.

This includes broad-based participation in our annual incentive plan, which rewards employees based on the company’s achievement of pre-established goals (or sales targets in the case of sales incentive plans) as well as performance against their personal objectives and our long-term equity incentive plans, which fosters an ownership culture and provides employees with the opportunity to share in the long-term success they help create.

We strive to create a culture of health and well-being throughout the organization by offering a diverse and customizable set of programs focusing on employee experience, self-care, work-life balance, flexibility and early intervention.

In addition to traditional employee benefits, we support employees and their families through access to a suite of innovative programs that are designed to enhance their physical, financial, emotional and social well-being.

• We provide a robust set of offerings centered around mental and emotional health including our employee assistance program, which provides employees and their family counseling support – from everyday matters to more serious ones.

• We offer an enhanced suite of differentiated global leave and time-off polices to address the needs of our diverse employee population through varying stages of life, including minimum standards for new parent leave (irrespective of gender or how a family is created), family caregiver leave and bereavement leave.

We also offer a global volunteer day to provide employees time off with full pay to give back to their communities.

• We recently introduced our Wellbeing Reimbursement Account, which reimburses employees for a wide array of expenses that support their overall wellbeing, empowering them to choose what is most important to them.

Workplace Safety & Employee Care .

Workplace safety is always a top priority for us.

To create and sustain a safe and healthy workplace, we have implemented initiatives designed to address risk evaluation, education and training of employees, use of appropriate personal protective equipment, and compliance with relevant national and international health and safety standards.

We leverage an employee support framework focused on Care, Connection, Continuity and Consciousness (our “4Cs”) to enable our employees to live into our values and support one another while doing everything we can to deliver on our patient mission.

Important to this framework are new leader expectations and tools given the rise and complexity of emerging employee demands and needs – including more flexibility to address personal needs, a greater connection to understand the whole person and their lives, and more active support surrounding social injustice.

This includes broad-based participation in our annual incentive plan, which rewards employees based on the company’s achievement of pre-established goals (or sales targets in the case of sales incentive plans) as well as performance against their personal objectives and our long-term equity incentive plans, which fosters an ownership culture and provides eligible employees with the opportunity to share in the long-term success they help create.

Fundamental to creating a high performing company is our commitment to building and maintaining a culture of health and wellbeing throughout the organization.

We do this by supporting employees and their families through access to a suite of innovative programs that inspire them to focus on their mind, body, finances and work/life balance.

• We provide a robust set of offerings centered on mental and emotional health, including resilience, stress management, mindfulness and managing clinical conditions.

• We offer programs that promote activity, healthy nutrition habits, chronic condition prevention and early detection of more serious disease/illness.

• We offer an enhanced suite of global paid leave and other time-off polices to address the differing needs of our employee population through varying stages of life, including minimum standards for new parent leave (irrespective of gender or how a family is created), family caregiver leave and bereavement leave.

We offer a global volunteer day to provide employees time off with full pay to give back to their communities.

• Our Wellbeing Reimbursement Account reimburses employees for a wide array of expenses that support their overall wellbeing, empowering them to choose what is most important to them.

• In 2025, we will hold our first-ever Jazz Wellbeing Week, providing dedicated time off to all employees to focus on wellbeing and self-care.

Employee Care .

We are committed to providing a great workplace experience where people feel invested in, valued and cared for, and a sense of belonging.

We strive to enable our employees to live into our values and support one another while doing everything we can to deliver on our patient mission.

Important to this are leader expectations and tools given the rise and complexity of emerging employee demands and needs – including more flexibility to address personal needs, a greater connection to understand the whole person and their lives, and creating supportive and productive work environments for people to thrive.

We provide productivity and collaboration tools and resources for employees working remotely, including training and toolkits to help leaders effectively lead and manage remote teams;

increased flexibility within work schedules and leave programs to support employees caring for children and others;

expanded employees assistance and mindfulness programs to help employees and their families manage anxiety, stress, and overall wellbeing;

expanded employees assistance and mindfulness programs

to help employees and their families manage anxiety, stress, and overall wellbeing;

and increased investment in resources focused on inclusion and belonging.

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In certain cases, such laws, directives and regulations may impose strict liability for pollution of the environment and contamination resulting from spills, disposals or other releases of hazardous substances or waste.

Costs, damages and/or fines may result from the presence, investigation and remediation of such contamination at properties currently or formerly owned, leased or operated by us or at off-site locations,

including where we have arranged for the disposal of hazardous substances or waste.

In addition, we may be subject to third party claims, including for natural resource damages, personal injury and property damage, in connection with such contamination.

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We and others have launched products to treat EDS in narcolepsy and may in the future launch products to treat cataplexy in narcolepsy that are competitive with or disrupt the market.

Xywav and Xyrem face competition from Lumryz, a branded product for treatment of cataplexy and/or EDS in narcolepsy.

Avadel’s Lumryz, a once-nightly dose, high-sodium oxybate, was launched in the U.S.

Xywav and Xyrem face competition from Avadel’s Lumryz, a branded product for treatment of cataplexy and/or EDS in narcolepsy.

Lumryz, a once-nightly dose, high-sodium oxybate, was launched in the U.S.

market in June 2023.

On June 22, 2023, we filed a complaint in the United States District Court for the District of Columbia seeking a declaration that FDA’s approval of the NDA for Avadel's Lumryz was unlawful.

In the complaint, we allege that FDA acted outside its authority under the Orphan Drug Act, when, despite ODE protecting Xywav, FDA approved the Lumryz NDA and granted Lumryz ODE based on FDA’s finding that Lumryz makes a major contribution to patient care, and is therefore clinically superior to Xywav and Xyrem.

We cannot at this time predict the timing or ultimate outcome of this litigation or the impact of this litigation on our sleep products, Xywav and Xyrem.

For additional information on litigation involving this matter, see “ FDA Litigation ” and “ Avadel Patent Litigation ” in Note 14, Commitments and Contingencies-Legal Proceedings of the Notes to Consolidated Financial Statements, included in Part IV of this Annual Report on Form 10‑K.

In addition, since January 2023 our oxybate products have faced competition from an AG version of high-sodium oxybate pursuant to a settlement agreement we entered into with an abbreviated new drug application, or ANDA, filer, and since July 2023, an additional AG version of high-sodium oxybate from a volume-limited ANDA filer.

Collectively, these AG version of high-sodium oxybate have negatively impacted and are expected to continue to negatively impact Xyrem and Xywav sales for patients with narcolepsy.

Specifically, a wholly owned subsidiary of Hikma Pharmaceuticals PLC, or Hikma, launched its AG version of sodium oxybate in January 2023 and Amneal Pharmaceuticals LLC, or Amneal, launched its AG version of sodium oxybate in July 2023.

We and Avadel are engaged in various litigation regarding Lumryz and our oxybate products.

We cannot at this time predict the timing or ultimate outcome of the litigation or the impact of the litigation on our sleep products, Xywav and Xyrem.

For additional information on litigation involving this matter, see “ FDA Litigation ” and “ Avadel Litigation ” in Note 13, Commitments and Contingencies-Legal Proceedings of the Notes to Consolidated Financial Statements, included in Part IV of this Annual Report on Form 10‑K.

In addition, since January 2023 our oxybate products have faced competition from AG high-sodium oxybate pursuant to a settlement agreement we entered into with an ANDA filer, and since July 2023, an additional AG version of

high-sodium oxybate from a volume-limited ANDA filer.

Collectively, these AG versions of high-sodium oxybate have negatively impacted and are expected to continue to negatively impact Xyrem and Xywav sales for patients with narcolepsy.

Specifically, a wholly owned subsidiary of Hikma launched its AG version of high-sodium oxybate in January 2023 and Amneal launched its AG version of high-sodium oxybate in July 2023.

Hikma has elected to continue to sell the Hikma AG product, with royalties to be paid to us, for a total of up to four years beginning in January 2024, which election may be terminated by Hikma in accordance with the notice provisions in the agreements between the parties.

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For a description of generic versions of sodium oxybate and/or new products for the treatment of cataplexy and/or EDS that currently compete or could in the future compete with, or otherwise disrupt the market for, Xywav and Xyrem, as well as a description of our settlement agreements with ANDA filers, see the risk factor under the heading “ The introduction of new products in the U.S.

market that compete with, or otherwise disrupt the market for, our oxybate

products has adversely affected and may continue to adversely affect sales of our oxybate products” in Part I, Item 1A of this Annual Report on Form 10‑K.

market that compete with, or otherwise disrupt the market for, our oxybate products has adversely affected and may continue to adversely affect sales of our oxybate products” in Part I, Item 1A of this Annual Report on Form 10‑K.

In addition, Xywav and Xyrem may face competition in the future from other new sodium oxybate formulations for treatment of narcolepsy.

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Non-oxybate products intended for the treatment of EDS or cataplexy in narcolepsy or IH (Xywav is the first and only FDA-approved therapy to treat IH), including new market entrants, even if not directly competitive with Xywav or Xyrem, could have the effect of changing treatment regimens and payor or formulary coverage of Xywav or Xyrem in favor of other products, and indirectly materially and adversely affect sales of Xywav and Xyrem.

Xywav and Xyrem face competition from Sunosi® (solriamfetol), which we sold to Axsome Therapeutics, Inc.

Xywav and Xyrem face competition from Sunosi, which we sold to Axsome in 2022.

Xywav and Xyrem may face increased competition from new branded entrants to treat EDS or cataplexy in narcolepsy such as pitolisant, which has been approved by FDA for the treatment of both cataplexy and EDS in adult patients with narcolepsy.

Harmony Biosciences has announced a phase 3 study for pitolisant for IH after receiving a refusal to file from FDA in February 2025.

Other companies have announced that they have product candidates in various phases of development to treat the symptoms of narcolepsy, such as Axsome’s reboxetine, and various companies are performing research on orexin agonists for the treatment of sleep disorders, including Takeda Pharmaceutical Company Limited, Merck & Co., Inc., Eisai Co., Ltd., Centessa Pharmaceuticals plc and Alkermes plc.

In addition, we are also aware that prescribers often prescribe branded or generic medications for cataplexy before prescribing or instead of prescribing oxybate therapy, and that payors often require patients to try such medications before they will cover Xywav or Xyrem, even if they are not approved for this use.

In addition, we are also aware that prescribers often prescribe branded or generic medications for cataplexy and IH before prescribing or instead of prescribing oxybate therapy, and that payors often require patients to try such medications before they will cover Xywav or Xyrem, even if they are not approved for this use.

For example, prescribers often treat mild cataplexy with drugs that have not been approved by FDA for this indication, including tricyclic antidepressants and selective serotonin reuptake inhibitors or selective norepinephrine reuptake inhibitors.

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FDA approved Marinus Pharmaceuticals, Inc.’s ganaxolone for the treatment of seizures associated with cyclin-dependent kinase-like 5 deficiency disorder in March 2022.

Ovid Therapeutics Inc./Takeda Pharmaceutical Company Limited and Eisai Company Limited are developing therapies for treating Developmental and Epileptic Encephalopathies (includes DS and LGS).

Stiripentol has been approved in Europe for several years to treat DS and was approved in 2018 by the FDA.

Zynerba Pharmaceuticals, Inc.

is developing a topical formulation of cannabidiol, or CBD, for which it is working with FDA on a path forward on CONNECT-FX data for Zygel in Fragile X syndrome.

There are a number of public and private companies in the early stages of developing genetic therapies for DS, including Stoke Therapeutics, Inc., which has an antisense oligonucleotide, STK-001, in early clinical trials.

Ovid Therapeutics Inc./Takeda Pharmaceutical Company Limited, Eisai Company Limited and H Lundbeck A/S are developing therapies for treating Developmental and Epileptic Encephalopathies (includes DS and LGS).

Stiripentol has been approved in Europe for several years to treat DS and was approved in 2018 by FDA.

Harmony Biosciences is developing a topical formulation of CBD for which it is working with FDA on a path forward on CONNECT-FX data for Zygel in Fragile X syndrome.

There are a number of public and private companies in various stages of developing genetic therapies for DS, including Stoke Therapeutics, Inc., which has an antisense oligonucleotide, STK-001, in clinical trials.

In addition, there are non-FDA approved CBD preparations being made available from companies in the medical marijuana industry, which might attempt to compete with Epidiolex.

While federal law prohibits the sale and distribution of most marijuana products not approved or authorized by FDA, the vast majority of states and the District of Columbia have legalized either CBD or marijuana for either recreational or medical use, or both.

While federal law prohibits the sale and distribution of most marijuana products not approved or authorized by FDA, the vast majority of states and the

District of Columbia have legalized either CBD or marijuana for either recreational or medical use, or both.

Under the U.S.

Farm Bill, enacted in late 2018, certain extracts and other material derived from cannabis are no longer controlled under the Federal Controlled Substances Act, or CSA.

Farm Bill, enacted in late 2018, certain extracts and other material derived from cannabis are no longer controlled under the CSA.

However, the marketing of such products as a food, dietary supplement, or for medical purposes remains subject to FDA requirements.

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In addition, Congressional efforts related to legalization of marijuana continue.

Although our business is distinct from that of entities marketing FDA-unapproved marijuana and CBD-containing dietary supplement, future legislation or federal government action authorizing the sale, distribution, use, and insurance reimbursement of non-FDA approved marijuana or CBD products could increase competition for and adversely affect our ability to generate sales of Epidiolex and our cannabinoid product candidates.

Although our business is distinct from that of entities marketing FDA-unapproved marijuana and CBD-containing dietary supplements, future legislation or federal government action authorizing the sale, distribution, use, and insurance reimbursement of non-FDA approved marijuana or CBD products could increase competition for and adversely affect our ability to generate sales of Epidiolex and our cannabinoid product candidates.

We are aware of exploratory research into the effects of tetrahydrocannabinol, often referred to as THC, and CBD drug formulations;

discovery research within the pharmaceutical industry into synthetic agonists and antagonists of

CB1 and CB2 receptors;

discovery research within the pharmaceutical industry into synthetic agonists and antagonists of CB1 and CB2 receptors;

companies that supply synthetic cannabinoids and cannabis extracts to researchers for pre-clinical and clinical investigation;

and various companies that cultivate cannabis plants with a view to supplying herbal cannabis or nonpharmaceutical cannabis-based formulations to patients.

These activities have not been approved by the FDA but may in the future compete with our products.

These activities have not been approved by FDA but may in the future compete with our products.

Moreover, we expect that Epidiolex will face competition from generic products in the future.

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Zepzelca faces competition from topotecan, which is also an approved treatment in second line SCLC in the U.S., as well as other regimens for relapsed SCLC currently recommended in compendia guidelines, including rechallenge with first line platinum chemotherapy.

There are also a number of products and immunotherapies for the treatment of second line SCLC in various phases of development, including Amgen Inc.’s tarlatamab.

There are also a number of products and immunotherapies for the treatment of second line SCLC in various phases of development, including Amgen Inc.’s tarlatamab, which was approved for use in the U.S.

Moreover, we expect that Zepzelca will face competition from generic products in the future.

In July and August 2024, we received notices from various ANDA filers that they have each filed with FDA an ANDA for a generic version of Zepzelca (lurbinectedin).

In September 2024, we filed patent infringement suits against these ANDA filers.

For a description of this litigation, see “ Zepzelca Patent Litigation ” in Note 13, Commitments and Contingencies-Legal Proceedings of the Notes to Consolidated Financial Statements, included in Part IV of this Annual Report on Form 10‑K.

As a result of these lawsuits, we expect that a stay of approval of up to 30 months will be imposed by FDA on these ANDA filers.

Rylaze may face competition from Erwinaze in the future.

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coli -derived asparaginase.

In April 2020, Porton Biopharma Limited, or PBL, granted Clinigen Group plc, or Clinigen, a global license for Erwinaze.

In April 2020, PBL granted Clinigen a global license for Erwinaze.

However, in December 2021, Clinigen announced that FDA issued a complete response letter to PBL’s BLA for Erwinaze, indicating that the BLA cannot be approved in its current form.

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midostaurin, enasidenib and ivosidenib), immunotherapies (e.g., gemtuzumab ozogamicin and chimeric antigen receptor T-cell therapy), and agents disrupting leukemia cell survival (e.g., glasdegib).

We are also aware of the increasing use of venetoclax combined with either a hypomethylating agent or low-dose cytarabine, a treatment approved by FDA in newly diagnosed AML patients who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.

We are also aware of the increasing use of venetoclax combined with either a hypomethylating

agent or low-dose cytarabine, a treatment approved by FDA in newly diagnosed AML patients who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.

With ongoing trends in the U.S.

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• Defitelio .

Defitelio is the first and only approved treatment for patients with VOD, sVOD, or VOD with renal or pulmonary dysfunction following HSCT by regulatory authorities in the U.S., Europe, Japan and other markets.

Utilization of Defitelio is in part driven by evolving treatment practices in HSCT.

While there is currently no direct competition to Defitelio to treat severe VOD, changes in the types of conditioning regimens used as part of HSCT may affect the incidence of VOD diagnosis and demand for Defitelio.

There was a significant decline in the number of patients receiving HSCT due to the effects of the COVID-19 pandemic.

Moving forward, while HSCT procedures are gradually returning to pre-pandemic numbers, we expect changes in chemotherapy regimens and the increasing use of cell therapies to potentially lower the incidence of sVOD;

additionally, there has been a reduction of prophylactic use of Defitelio in Europe.

In December 2024, FDA accepted an ANDA for a generic version of Defitelio (defibrotide sodium).

We have yet to receive notice of this ANDA filing.

Ziihera faces competition from generic chemotherapies, including cisplatin/gemcitabine rechallenge, and other HER2 directed therapies, including Enhertu and trastuzumab.

An important part of our corporate strategy is to build a diversified product pipeline, including by acquiring or in-licensing and developing, or partnering to license and develop, additional products and product candidates that we believe are highly differentiated and have significant commercial potential.

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Also in the U.S., Epidiolex is sold to specialty pharmacies, wholesalers and specialty distributors.

is sold to hospital customers through subsidiary specialty distributors of McKesson Corporation, or McKesson.

Zepzelca, Rylaze and Vyxeos are sold to customers through subsidiary specialty distributors of McKesson, Cencora, Inc.

(formerly named AmerisourceBergen Corporation), or Cencora, and Cardinal Health, Inc., or Cardinal.

We have distribution services agreements made in the ordinary course of business with McKesson, Cencora and Cardinal and a pharmacy services agreement with ESSDS that provides for the distribution of Xywav and Xyrem to patients.

For more information regarding our relationship with ESSDS, see “Business—Our Commercialized Products—Xyrem” in this Part I, Item 1.

Defitelio is sold to hospital customers through subsidiary specialty distributors of McKesson.

Zepzelca, Rylaze, Vyxeos and Ziihera are sold to customers through subsidiary specialty distributors of McKesson, Cencora, and Cardinal.

We have distribution services agreements made in the ordinary course of business with McKesson, Cencora and Cardinal and a pharmacy services agreement with ESSDS.

For more information regarding our relationship with ESSDS, see “Business—Our Commercialized Products—Xywav and Xyrem REMS” in this Part I, Item 1.

Purchases are made on a purchase order basis.

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We commercialize and distribute Xyrem in Canada for the treatment of cataplexy in patients with narcolepsy.

Xyrem is also sold in 21 countries by UCB (which has rights to market Xyrem in 54 countries).

Xyrem is also sold in certain countries outside the U.S.

and Canada by UCB under the UCB license.

In July 2024, the parties agreed to terminate the UCB license.

UCB has up to two years from the execution of the termination agreement to withdraw the marketing authorization for Xyrem in all applicable territories.

Manufacturing

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where we produce Epidiolex/Epidyolex, and a manufacturing plant in Villa Guardia, Italy where we produce defibrotide drug substance.

We currently do not have our own commercial manufacturing or packaging capability for our other products, product candidates or their active pharmaceutical ingredients, or APIs.

We currently do not have our own commercial manufacturing or packaging capability for our other products, product candidates or their APIs.

As a result, our ability to develop and supply products in a timely and competitive manner depends on third party suppliers being able to meet our ongoing commercial and clinical trial needs for API, other raw materials, packaging materials and finished products.

Lead Marketed Products

Marketed Products

Xywav is manufactured at our Athlone facility.

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The API of Xywav are the calcium, magnesium, potassium and sodium salts of gamma-hydroxybutyric acid (as gamma-hydroxybutyric acid is the API for Xyrem), which are Schedule I controlled substances in the U.S.

As a result, Xywav and Xyrem are subject to regulation by the U.S.

Drug Enforcement Administration, or DEA, under the CSA, and its manufacturing and distribution are highly restricted.

As a result, Xywav and Xyrem are subject to regulation by the DEA under the CSA, and its manufacturing and distribution are highly restricted.

Quotas from the DEA are required in order to manufacture or procure calcium, magnesium, potassium and sodium salts of gamma-hydroxybutyric acid in the U.S.

For information related to DEA quota requirements, see “Business—Government Regulation—Other Post-Approval Pharmaceutical Product Regulation—Controlled Substance Regulations” in this Part I, Item 1.

Xyrem is manufactured by us in our Athlone facility and by Patheon Pharmaceuticals Inc., which we refer to together with its affiliates as Patheon, under a Master Manufacturing Services Agreement, or the Patheon Agreement, entered into with Patheon in 2015.

For information related to DEA quota requirements, see “Business—Government

Regulation—Other Post-Approval Pharmaceutical Product Regulation—Controlled Substance Regulations” in this Part I, Item 1.

Xyrem is manufactured by us in our Athlone facility and by Patheon under the Patheon Agreement entered into with Patheon in 2015.

We manufacture Xyrem in our Athlone facility for most of our U.S.

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In addition, we may terminate the Patheon Agreement for any reason upon 12 months’ prior written notice.

Siegfried USA, LLC and its European affiliates, or Siegfried, supply sodium oxybate, the API of Xyrem, to Patheon and our Athlone facility.

Siegfried supply sodium oxybate, the API of Xyrem, to Patheon and our Athlone facility.

Although Siegfried has been our only supplier of sodium oxybate since 2012, we have the right to purchase a portion of our worldwide requirements of sodium oxybate from other suppliers.

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under highly controlled and standardized conditions.

Zepzelca is manufactured by Simtra Biopharma Solutions, or Simtra.

Zepzelca is manufactured by Simtra.

The current term of the agreement with Simtra will expire in December 2025 and will then be subject to automatic two-year extensions, unless either party provides advance notice of its intent to terminate the agreement.

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If Patheon does not or is not able to supply us with Defitelio for any reason, it may take time and resources to implement and execute the necessary technology transfer to another processor, and such delay could negatively impact our anticipated revenues from Defitelio and could potentially cause us to breach contractual obligations with customers or to violate local laws requiring us to deliver the product to those in need.

Ziihera is manufactured by WuXi Biologics (Hong Kong) Limited at their manufacturing site in WuXi, China.

The initial term of the agreement with WuXi will expire in March 2029 and will then be subject to automatic three year extensions, unless either party provides advance notice of its intent to terminate the agreement.

We have the right to appoint an alternate contract manufacturer at our discretion.

Product Candidates

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Patents extend for varying periods according to the date of the patent filing or grant and the legal term of patents in the various countries where patent protection is obtained.

The patent laws of non-U.S.

countries differ from those in U.S., and the degree of protection afforded by non-U.S.

The patent laws of ex-U.S.

countries differ from those in U.S., and the degree of protection afforded by ex-U.S.

patents may be different from the protection offered by U.S.

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In addition, we have patent applications that relate to Xywav for use in additional indications that would, if issued, expire between 2040 and 2041.

Xywav has been granted ODE by FDA to treat narcolepsy through 2027 and to treat IH through 2028.

Xywav has been granted ODE by FDA to treat narcolepsy through January 2028 (inclusive of six months of pediatric exclusivity) and to treat IH through August 2028.

Some of our Xywav patents have been subject to patent litigation with the companies who filed ANDAs seeking to market a generic version of Xywav.

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For additional information on litigation involving these matters, see Note 13, Commitments and Contingencies-Legal Proceedings of the Notes to Consolidated Financial Statements, included in Part IV of this Annual Report on Form 10‑K.

We currently have six issued patents in the U.S.

relating to Xyrem listed in FDA’s publication “Approved Drug Products with Therapeutic Equivalence Evaluations,” or the Orange Book.

Our patents relate to Xyrem’s restricted distribution system and a drug-drug interaction, or DDI, between Xyrem and divalproex sodium.

In October 2018, as a result of FDA’s grant of pediatric exclusivity, an additional six months was added to the original expiration dates of all of our Orange Book-listed patents that existed at that time.

We currently have seven issued patents in the U.S.

relating to Xyrem listed in the Orange Book.

Our patents relate to a DDI between Xyrem and divalproex sodium.

In October 2018, due to FDA’s grant of pediatric exclusivity, an additional six months was added to the original expiration dates of all of our Orange Book-listed patents that existed at that time.

As a result, our Orange Book-listed patents have periods of exclusivity between December 2022 (with an additional six months for pediatric exclusivity) and September 2033.

Some of our Xyrem patents have been subject to patent litigation with the companies who filed

ANDAs seeking to market a generic version of Xyrem, including challenge through the inter partes review, or IPR, procedures of the Patent Trial and Appeal Board, or PTAB, of the U.S.

Patent and Trademark Office, or USPTO.

Some IPR petitions were dismissed by the PTAB.

Some of our Xyrem patents have been subject to patent litigation with the companies who filed ANDAs seeking to market a generic version of Xyrem, including challenge through the IPR procedures of the PTAB.

The PTAB dismissed some of the IPR petitions.

However, in July 2018, the United States Court of Appeals for the Federal Circuit upheld on appeal PTAB decisions finding that six patents associated with the Xywav and Xyrem REMS and three claims of a seventh REMS patent were unpatentable.

As a result, we will not be able to enforce patents or claims that the PTAB found unpatentable.

Although we have settled all patent litigation against the ten companies that filed ANDAs, it is possible that additional companies may challenge our U.S.

Although we have settled all patent litigation against the ten companies that filed ANDAs, additional companies may challenge our U.S.

patents for Xyrem in the future.

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For additional information on litigation involving or Orange Book-listed patents, see “ Avadel Patent Litigation ” in Note 14, Commitments and Contingencies-Legal Proceedings of the Notes to Consolidated Financial Statements, included in Part IV of this Annual Report on Form 10‑K.

A Xyrem formulation patent that had issued in multiple non-U.S.

countries expired in 2019.

The European Patent Office has issued a method of administration patent relating to the DDI between Xyrem and divalproex sodium that will expire in 2034.

That patent is licensed to UCB as the marketing authorization holder outside of the U.S.

and Canada, and UCB has the right to enforce it.

In addition to our issued patents, we have patent applications relating to Xyrem pending in the U.S.

and other countries.

For additional information on litigation involving our Orange Book-listed patents, see “ Avadel Litigation ” in Note 13, Commitments and Contingencies-Legal Proceedings of the Notes to Consolidated Financial Statements, included in Part IV of this Annual Report on Form 10‑K.

The European Patent Office issued a method of administration patent relating to the DDI between Xyrem and divalproex sodium that expires in 2034.

Our patent portfolio relating to the use of CBD in the treatment of epileptic encephalopathies includes 32 issued U.S.

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We have filed corresponding patent applications in many jurisdictions worldwide, including Europe, U.K., Canada, Japan, Mexico, Australia and New Zealand.

The USPTO has granted a patent based on data that demonstrates that Epidiolex provides a benefit over synthetic CBD in an animal model of epilepsy, which will expire in 2039 and we have listed it in the Orange Book.

The USPTO has granted two patents based on data that demonstrates that Epidiolex provides a benefit over synthetic CBD in an animal model of epilepsy, which will expire in 2039 and which are listed in the Orange Book.

Epidiolex has received ODE to treat seizures associated with LGS and DS through 2025 and TSC through 2027.

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Zepzelca has also been granted ODE for the treatment of adults with metastatic SCLC with disease progression on or after platinum-based chemotherapy until 2027 and new chemical entity exclusivity until 2025 in the U.S.

In 2016, we obtained worldwide rights from Pfenex, Inc., or Pfenex, including Pfenex’s patent rights relating to Rylaze, to develop and commercialize multiple early-stage hematology product candidates, including a license to two U.S.

In July and August 2024, we received notices from various ANDA filers that they have each filed with FDA an ANDA for a generic version of Zepzelca (lurbinectedin).

In September 2024, we filed patent infringement suits against these ANDA filers.

As a result of these lawsuits, we expect that a stay of approval of up to 30 months will be imposed by FDA on these ANDA filers.

In 2016, we obtained worldwide rights from Pfenex, including Pfenex’s patent rights relating to Rylaze, to develop and commercialize multiple early-stage hematology product candidates, including a license to two U.S.

process patents relating to Rylaze, with respective expirations in 2026 and 2038.

Pfenex has been acquired by Ligand Pharmaceuticals Incorporated.

Pfenex has been acquired by Ligand.

Rylaze has been granted orphan drug designation for the treatment of patients with ALL or LBL.

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These patents are listed in the Orange Book.

Vyxeos has been granted ODE by FDA until August 2024, seven years from its FDA approval, for the treatment of adults with newly-diagnosed t-AML or AML-MRC.

FDA granted Vyxeos ODE for the treatment of adults with newly-diagnosed t-AML or AML-MRC, which expired in August 2024.

In March 2021, FDA approved an expanded label for Vyxeos for the treatment of t-AML or AML-MRC in pediatric patients 1 year and older.

In addition, Vyxeos has

been granted orphan drug designation by the EC until August 2028, ten years from its EC approval for the treatment of adults with newly-diagnosed t-AML or AML-MRC and was approved by Health Canada for treatment of adults with newly diagnosed t-AML or AML-MRC in April 2021.

In addition, Vyxeos was granted OME by the EC until August 2028, ten years from its EC approval for the treatment of adults with newly-diagnosed t-AML or AML-MRC.

Vyxeos was approved by Health Canada for treatment of adults with newly diagnosed t-AML or AML-MRC in April 2021.

Vyxeos was approved in March 2024 in Japan and designated as an orphan drug.

• Defitelio .

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patents are listed in the Orange Book.

Defibrotide has also been granted orphan drug designation by the Korean Ministry of Food and Drug Safety to treat and prevent VOD, by the Commonwealth of Australia-Department of Health for the treatment of VOD and by the EC for the prevention of acute Graft-versus-Host Disease and has also received approvals in Canada, Brazil and Switzerland.

In December 2024, FDA accepted an ANDA for a generic version of Defitelio (defibrotide sodium).

We have yet to receive notice of this ANDA filing.

We acquired the rights to defibrotide for the treatment and prevention of VOD in North America, Central America and South America from Sigma-Tau Pharmaceuticals, Inc.

The patents and/or patent applications that relate to our product candidates include:

• Zanidatamab .

Through a license agreement with Zymeworks BC Inc.

in 2022, we obtained a license to a portfolio of U.S.

patents and patent applications, including rights relating to compositions and methods of using zanidatamab.

In 2022, we obtained a license from Zymeworks BC Inc., which included rights to a portfolio of U.S.

patents and patent applications, including compositions and methods of using Ziihera.

The portfolio contains a U.S.

composition of matter patent relating to zanidatamab, which expires in 2034 (excluding any adjustments or extensions).

composition of matter patent relating to Ziihera, which expires in 2034 (excluding any adjustments or extensions).

The patents and/or patent applications that relate to our product candidates include:

Through a collaboration agreement and an asset purchase agreement with Redx in 2019, we acquired a portfolio of U.S.

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for a drug or biologic product candidate generally includes:

• conducting preclinical laboratory and animal testing and submitting the results to FDA in an investigational new drug, or IND, application requesting approval to test the product candidate in human clinical trials;

• conducting preclinical laboratory and animal testing and submitting the results to FDA in an IND application requesting approval to test the product candidate in human clinical trials;

• conducting adequate and well-controlled human clinical trials to establish the safety and efficacy of the product candidate in the desired indication;

• submitting an NDA, supplemental New Drug Application, or sNDA or BLA as appropriate, to FDA seeking approval for a specific indication;

• completing inspections by FDA of the facilities where the product candidate is manufactured, analyzed and stored to demonstrate compliance with current Good Manufacturing Practices, or cGMP, and any requested FDA audits of the clinical trial sites that generated the data supporting the application.

• submitting an NDA, sNDA, BLA or sBLA as appropriate, to FDA seeking approval for a specific indication;

• completing inspections by FDA of the facilities where the product candidate is manufactured, analyzed and stored to demonstrate compliance with cGMP, and any requested FDA audits of the clinical trial sites that generated the data supporting the application.

Human clinical trials conducted before approval of a product generally proceed in three sequential phases, although the phases may overlap.

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FDA enforces good clinical practices through periodic inspections of trial sponsors, clinical investigators and trial sites.

Once an NDA, sNDA or BLA has been compiled and submitted, FDA performs an initial review before it accepts the application for filing.

Once an NDA, sNDA, BLA or sBLA has been compiled and submitted, FDA performs an initial review before it accepts the application for filing.

FDA may refuse to file an application and/or request additional information before acceptance.

Once accepted for filing, FDA begins an in-depth review of the application.

Under the current goals and policies agreed to by FDA under the Prescription Drug User Fee Act, or PDUFA, for a new molecular entity, FDA has ten months from the filing decision in which to complete its initial review of a standard application and respond to the applicant, and six months from the filing decision for a priority application.

Under the current goals and policies agreed to by FDA under the PDUFA for a new molecular entity, FDA has ten months from the filing decision in which to complete its initial

review of a standard application and respond to the applicant, and six months from the filing decision for a priority application.

FDA does not always meet its PDUFA goal dates, and in certain circumstances, the PDUFA goal date may be extended.

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For example, FDA granted Vyxeos Breakthrough Therapy and Fast Track designations and granted Priority Review with respect to our NDA for Vyxeos for the treatment of t-AML and AML-MRC that was approved in August 2017.

In addition, a priority review voucher, or PRV, may be used to obtain priority review by FDA for one of our future regulatory submissions.

We used the PRV we acquired in May 2018 to obtain priority review for our Xywav for the treatment of IH sNDA, which was approved by FDA in August 2021.

In addition, a PRV may be used to obtain priority review by FDA for one of our future regulatory submissions.

We used the PRV we acquired in May 2018 to obtain priority review for our Xywav sNDA for the treatment of IH, which was approved by FDA in August 2021.

In June 2020, FDA granted Accelerated Approval to Zepzelca for relapsed SCLC.

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For example, as a condition of approval, FDA may require the sponsor to agree to certain post-marketing requirements, such as conducting Phase 4, or post-approval, clinical trials to gain additional safety data or to document a clinical benefit in the case of products approved under Accelerated Approval regulations.

FDA’s approval of the NDA for Defitelio included a number of post-marketing commitments and requirements, including the requirement that we conduct a clinical trial to analyze the safety of defibrotide versus best supportive care in the prevention of VOD in adult and

pediatric patients.

For its approval of Vyxeos, FDA required that we conduct a safety study to characterize infusion-related reactions in patients treated with Vyxeos and a clinical trial to determine dosing to minimize toxicity in patients with moderate and severe renal impairment.

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In the EU, there are several procedures for requesting marketing authorization which can be more efficient than applying for authorization on a country-by-country basis.

There is a “centralized” procedure allowing submission of a single marketing authorization application to the European Medicines Agency, or EMA.

If the EMA issues a positive opinion, the EC will grant a centralized marketing authorization that is valid in all EU member states and three of the four European Free Trade Association countries (Iceland, Liechtenstein and Norway).

There is a “centralized” procedure allowing submission of a single marketing authorization application to EMA.

If EMA issues a positive opinion, the EC will grant a centralized marketing authorization that is valid in all EU member states and three of the four European Free Trade Association countries (Iceland, Liechtenstein and Norway).

The centralized procedure is mandatory for certain medicinal products, including orphan medicinal products and biotechnology-derived medicinal products, and optional for others.

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To mitigate the immediate impact of this in December 2020, the EU and U.K.

reached an agreement in principle on the framework for their future relationship, the EU-U.K.

Trade and Cooperation Agreement, or TCA.

reached an agreement in principle on

the framework for their future relationship, the EU-U.K.

With regard to EU regulations, Northern Ireland continues to follow the EU regulatory rules.

As part of the TCA, the EU and the U.K.

recognize Good Manufacturing Practice, or GMP, inspections carried out by the other party and the acceptance of official GMP documents issued by the other party.

recognize GMP, inspections carried out by the other party and the acceptance of official GMP documents issued by the other party.

The TCA also encourages, although it does not oblige, the parties to consult one another on proposals to introduce significant changes to technical regulations or inspection procedures.

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The marketing authorization in the EU for Defitelio was granted under exceptional circumstances because it was not possible to obtain complete information about the product due to the rarity of the disease and because ethical considerations prevented conducting a study directly comparing Defitelio with best supportive care or a placebo.

As a result, the marketing authorization requires us to comply with a number of post-marketing obligations, including obligations relating to the manufacture of the drug substance and finished product, the submission of data concerning patients treated with the product collected through a third-party patient registry and the establishment of a multi-center, multinational and prospective observational patient registry to investigate the

long-term safety, health outcomes and patterns of utilization of Defitelio during normal use.

We are in the process of conducting the post-authorization study in the EU to provide further data on long-term safety, health outcomes and patterns of utilization of Defitelio in normal use.

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The manufacturing process for pharmaceutical products is highly regulated, and regulators may shut down manufacturing facilities that they believe do not comply with regulations.

We and the third party suppliers of our products are subject to cGMP, which are extensive regulations governing manufacturing processes, stability testing, recordkeeping and quality standards as defined by FDA, the EC, the EMA, competent authorities of EU member states and other regulatory authorities.

We and the third party suppliers of our products are subject to cGMP, which are extensive regulations governing manufacturing processes, stability testing, recordkeeping and quality standards as defined by FDA, the EC, EMA, competent authorities of EU member states and other regulatory authorities.

FDA also periodically inspects manufacturing facilities and the sponsor’s and manufacturer’s records related to manufacturing, and assesses compliance with cGMP.

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In the EU, a manufacturing authorization is required to manufacture medicinal products, and the manufacturing authorization holder must comply with various requirements set out in applicable EU laws, regulations and guidance.

These requirements include compliance with EU cGMP standards when manufacturing products and their APIs, including APIs manufactured outside of the EU with the intention of importing them into the EU.

These requirements include compliance with EU cGMP standards when manufacturing products and their APIs, including APIs

manufactured outside of the EU with the intention of importing them into the EU.

In addition to inspection reports, manufacturers and marketing authorization holders may be subject to civil, criminal or administrative sanctions, including suspension of manufacturing authorization, in cases of non-compliance with the EU or EU member states’ requirements applicable to manufacturing.

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In the EU, the advertising and promotion of our products are subject to laws governing promotion of medicinal products, interactions with physicians, misleading and comparative advertising and unfair commercial practices.

For example, applicable laws require that promotional materials and advertising in relation to medicinal products comply with the product’s Summary of Product Characteristics, or SmPC, as approved by the competent authorities in connection with a marketing authorization approval.

For example, applicable laws require that promotional materials and advertising in relation to medicinal products comply with the product’s SmPC as approved by the competent authorities in connection with a marketing authorization approval.

The SmPC is the document that provides information to physicians concerning the safe and effective use of the product.

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The statute has been interpreted to apply to arrangements between pharmaceutical companies on one hand and patients, prescribers, purchasers and formulary managers on the other.

Although there are a number of statutory exemptions and regulatory safe harbors protecting certain common manufacturer business arrangements and activities from prosecution and administrative sanction, the exemptions and safe harbors are drawn narrowly and are subject to regulatory revision or changes in interpretation by the U.S.

Department of Justice, or DOJ, and the Office of Inspector General of the U.S.

Department of Health and Human Services, or OIG.

Practices or arrangements that involve remuneration may be subject to scrutiny if they do not qualify for an exemption or safe harbor.

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Violations of the federal Anti-Kickback Statute may be established without providing specific intent to violate the statute, and may be punishable by civil, criminal, and administrative fines and penalties, damages, imprisonment, and/or exclusion from participation in federal healthcare programs.

The federal civil False Claims Act prohibits, among other things, any person from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment of federal funds, or knowingly making, or causing to be made, a false statement to get a false claim paid.

A claim resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim.

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Pharmaceutical companies are subject to other federal false claim and statements laws, some of which extend to non-government health benefit programs.

For example, the healthcare fraud provisions under the Health Insurance Portability and Accountability Act of 1996 and its implementing regulations, or HIPAA, impose criminal liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any health care benefit program, including private third party payors, or falsifying or covering up a material fact or making any materially false or fraudulent statement in connection with the delivery of or payment for health care benefits, items or services.

For example, the healthcare fraud provisions under HIPAA impose criminal liability for,

among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any health care benefit program, including private third party payors, or falsifying or covering up a material fact or making any materially false or fraudulent statement in connection with the delivery of or payment for health care benefits, items or services.

Violations of HIPAA fraud provisions may result in criminal, civil and administrative penalties, fines and damages, including exclusion from participation in federal healthcare programs.

The majority of individual states also have statutes or regulations similar to the federal anti-kickback law and the False Claims Act, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.

The majority of individual states also have statutes or regulations similar to the federal Anti-Kickback Statute and the False Claims Act, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.

Other states restrict whether and when pharmaceutical companies may provide meals to health care professionals or engage in other marketing-related activities, and certain states and cities require identification or licensing of sales representatives.

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Safety Reporting/Pharmacovigilance

FDA, the EMA and other governmental authorities track information on side effects and adverse events reported during clinical studies and after marketing approval.

FDA, EMA and other governmental authorities track information on side effects and adverse events reported during clinical studies and after marketing approval.

We are required to file periodic safety update reports with the authorities concerning adverse events.

If, upon review, an authority determines that any events and/or reports indicate a trend or signal, they can require a change in a product label, restrict sales and marketing, require post-approval safety studies, require a labor intensive collection of data regarding the risks and benefits of marketed products and ongoing assessments of those risks and benefits and/or require or conduct other actions, potentially including withdrawal or suspension of the product from the market.

For example, if the EMA has concerns that the risk-benefit profile of a product has changed, it can, following an investigation procedure, adopt an opinion advising that the existing marketing authorization for the product be varied or suspended and requiring the marketing authorization holder to conduct post-authorization safety studies.

The opinion is then submitted for

approval by the EC.

For example, if EMA has concerns that the risk-benefit profile of a product has changed, it can, following an investigation procedure, adopt an opinion advising that the existing marketing authorization for the product be varied or suspended and requiring the marketing authorization holder to conduct post-authorization safety studies.

The opinion is then submitted for approval by the EC.

Also, from time to time, FDA issues drug safety communications on its adverse event reporting system based on its review of reported adverse events.

FDA and the competent authorities of the EU member states on behalf of the EMA also periodically inspect our records related to safety reporting.

FDA and the competent authorities of the EU member states on behalf of EMA also periodically inspect our records related to safety reporting.

Following such inspections, FDA may issue notices on FDA Form 483 and warning letters that could cause us to modify certain activities.

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Failure to adequately and promptly correct the observation(s) can result in a warning letter or other regulatory enforcement action.

Similarly, the EMA’s Pharmacovigilance Risk Assessment Committee may propose to the Committee for Medicinal Products for Human Use that the marketing authorization holder be required to take specific steps.

Similarly, EMA’s Pharmacovigilance Risk Assessment Committee may propose to the Committee for Medicinal Products for Human Use that the marketing authorization holder be required to take specific steps.

Non-compliance can lead to the variation, suspension or withdrawal of marketing authorization or imposition of financial penalties or other enforcement measures.

Sunshine Act and Transparency Laws

The Physician Payment Sunshine Act requires tracking of payments and transfers of value to physicians and teaching hospitals and ownership interests held by physicians and their families, and reporting to the federal government and public disclosure of these data.

The Sunshine provisions require tracking of payments and transfers of value to physicians and teaching hospitals and ownership interests held by physicians and their families, and reporting to the federal government and public disclosure of these data.

Since 2022, reporting has been required of information regarding payments and transfers of value provided to physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, and certified nurse-midwives.

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Controlled substances that are pharmaceutical products are subject to a high degree of regulation under the CSA, which establishes, among other things, certain registration, manufacturing quotas, security, recordkeeping, reporting, import, export and other requirements administered by the DEA.

The DEA classifies controlled substances into five schedules.

Schedule I substances by definition have a high potential for abuse, have no currently “accepted medical use” in the U.S., lack accepted safety for use under medical supervision, and may not be prescribed, marketed or sold in the U.S.

The DEA classifies controlled substances into five

Schedule I substances have a high potential for abuse, have no currently “accepted medical use” in the U.S., lack accepted safety for use under medical supervision, and may not be prescribed, marketed or sold in the U.S.

Pharmaceutical products approved for use in the U.S.

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We also require DEA quotas for Patheon to manufacture and procure the API of Xywav oxybate salt.

Xywav and Xyrem manufactured at our plant in Ireland enters the U.S.

as a Schedule III drug and thus does not require a DEA manufacturing or procurement quota.

Xywav and Xyrem manufactured at our plant in Ireland enter the U.S.

as Schedule III drugs and therefore do not require a DEA manufacturing or procurement quota.

As Schedule III drugs, Xywav and Xyrem are also subject to DEA and state regulations relating to the importation, manufacturing, storage, distribution and physician prescription procedures, including limitations on prescription refills.

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Our business activities outside of the U.S.

are subject to the U.S.

Foreign Corrupt Practices Act, or FCPA, and similar anti-bribery or anti-corruption laws, regulations, industry self-regulation codes of conduct and physicians’ codes of professional conduct or rules of other countries in which we operate, including the U.K.

Bribery Act of 2010, or the U.K.

are subject to the FCPA, and similar anti-bribery or anti-corruption laws, regulations, industry self-regulation codes of conduct and physicians’ codes of professional conduct or rules of other countries in which we operate, including the U.K.

The FCPA and similar anti-corruption laws in other countries generally prohibit the offering, promising, giving, or authorizing others to give anything of value, either directly or indirectly, to U.S.

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Bribery Act and similar laws.

Recently the Securities and Exchange Commission, or SEC, and the DOJ have increased their FCPA enforcement activities with respect to pharmaceutical companies.

Recently the SEC, and the DOJ have increased their FCPA enforcement activities with respect to pharmaceutical companies.

In addition, under the Dodd-Frank Wall Street Reform and Consumer Protection Act, private individuals who report to the SEC original information that leads to successful enforcement actions may be eligible for a monetary award.

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However, there is no certainty that all employees and third party business partners (including our distributors, wholesalers, agents, contractors, and other partners) will comply with anti-bribery laws.

In particular, we do not control the actions of our suppliers and other third party agents, although we may be liable for their actions.

particular, we do not control the actions of our suppliers and other third party agents, although we may be liable for their actions.

Violation of these laws may result in civil or criminal sanctions, which could include monetary fines, criminal penalties, disgorgement of past profits, and could cause disruption to our business, including through procurement bans or similar administrative actions.

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The legislative and regulatory landscape for privacy and data security continues to evolve with an increased attention in countries globally that could potentially affect our business.

In particular, we are subject to the EU General Data Protection Regulation, which imposes penalties up to 4% of annual global revenue, the California Consumer Privacy Act of 2018 and numerous other federal, state, national and international laws and regulations that govern the privacy and security of the personal data we collect and maintain.

In particular, we are subject to the EU General Data Protection Regulation, which imposes penalties up to 4% of annual global revenue, the California Consumer Privacy Act of 2018, as amended by the California Consumer Privacy Rights Act, and numerous other federal, state, national and international laws and regulations that govern the privacy and security of the personal data we collect and maintain.

These laws and regulations applicable to our business, increase potential enforcement and litigation activity.

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is premised on the applicant being the owner of, or having obtained a right of reference to, all of the data required to prove the safety and effectiveness of a drug product.

This type of marketing application, sometimes referred to as a “full” or “stand-alone” NDA, is governed by Section 505(b)(1) of the United

States Federal Food, Drug, and Cosmetic Act, or FDCA.

This type of marketing application, sometimes referred to as a “full” or “stand-alone” NDA, is governed by Section 505(b)(1) of the FDCA.

A Section 505(b)(1) NDA contains full reports of investigations of safety and effectiveness, which includes the results of preclinical and clinical trials, together with detailed information on the manufacture and composition of the product, in addition to other information.

As an alternative, the Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, provides two abbreviated approval pathways for certain drug products.

The first path, under Section 505(b)(2) of the FDCA, usually is used for the approval of a product that is similar, but not identical, to a previously-approved brand-name product, referred to as the reference listed drug, or RLD.

As an alternative, the Hatch-Waxman Act provides two abbreviated approval pathways for certain drug products.

Under this path, the applicant is permitted to rely to some degree on FDA’s finding that the RLD is safe and effective and must submit its own product-specific data on safety and effectiveness only to the extent necessary to bridge the differences between the products.

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The overall ten-year period may be extended for a further year to a maximum of 11 years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.

In April 2023, the European Commission proposed the “Pharmaceutical Package”, which aims to revise and replace existing pharmaceutical legislation to enhance the availability, accessibility, and affordability of medicinal products across the EU.

This package includes a proposal for a new directive and a new regulation that would replace the current pharmaceutical legislation in the EU.

Among others, the standard data protection period is proposed to decrease from eight to six years but would allow extensions of up to 12 years if specific conditions are met.

As of January 2025, the legislative process is ongoing.

Once an agreement is reached between the Council and the European Parliament, the legislation will be formally adopted and published.

Its adoption is likely to occur in 2026, with implementation following thereafter.

Orphan Drug and Other Exclusivities

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ODE does not prevent approval of another sponsor’s application for different indications or uses of the same drug, or for different drugs for the same indication.

Defibrotide has been granted ODE by FDA to treat and prevent VOD until March 2023.

Vyxeos has been granted ODE by FDA for the treatment of AML until August 2024.

Defibrotide was granted ODE by FDA to treat and prevent VOD until March 2023.

Vyxeos was granted ODE by FDA for the treatment of AML until August 2024.

Epidiolex has received ODE to treat seizures associated with LGS and DS through 2025 and TSC through 2027.

In June 2021, FDA, recognized seven years of ODE for Xywav stating that Xywav is clinically superior to Xyrem by means of greater safety due to reduced chronic sodium burden.

Xywav has been granted ODE by FDA to treat narcolepsy through 2027 and to treat IH through 2028.

Xywav has been granted ODE by FDA to treat narcolepsy through January 2027 and to treat IH through August 2028.

Rylaze has been granted ODE for the treatment of patients with ALL or LBL until 2028.

Biologic products approved under a BLA are subject to the Biologics Price Competition and Innovation Act, or BPCIA, which authorizes an abbreviated approval pathway for a biological product that is “biosimilar” to an already approved biologic, or reference product.

Biologic products approved under a BLA are subject to the BPCIA, which authorizes an abbreviated approval pathway for a biological product that is “biosimilar” to an already approved biologic, or reference product.

The BPCIA provides periods of exclusivity that protect a reference product from competition by biosimilars.

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In October 2018, FDA approved the sNDA and notified us that we had been granted pediatric exclusivity, extending by six months the preclusive effect of our Orange Book-listed patents for Xyrem, as well as the three-year regulatory exclusivity period granted to the Xyrem pediatric indication because of the clinical studies that were necessary for approval of the sNDA.

In the EU, orphan drug designation may be granted to products that can be used to treat life-threatening diseases or chronically debilitating conditions with an incidence of no more than five in 10,000 people or that, for economic reasons, would be unlikely to be developed without incentives.

Orphan designated medicinal products are entitled to a range of benefits during the development and regulatory review process and ten years of market exclusivity in all EU member states upon approval.

As in the U.S., a similar medicinal product with the same orphan indication may be approved, notwithstanding orphan product exclusivity, if the exclusivity holder gives consent or if the manufacturer of the original orphan medicinal product is unable to supply sufficient quantities.

In the EU, orphan designation may be granted to products that can be used to treat life-threatening diseases or chronically debilitating conditions with an incidence of no more than five in 10,000 people or that, for economic reasons, would be unlikely to be developed without incentives.

Orphan designated medicinal products are entitled to a range of benefits during the development and regulatory review process and ten years of OME in all EU member states upon approval.

As in the U.S., a similar medicinal product with the same orphan indication may be approved, notwithstanding OME, if the exclusivity holder gives consent or if the manufacturer of the original orphan medicinal product is unable to supply sufficient quantities.

Marketing authorization may also be granted to a similar medicinal product with the same orphan indication if the similar product is deemed safer, more effective or otherwise clinically superior to the original orphan medicinal product.

The period of market exclusivity granted in relation to the original orphan medicinal product may, in addition, be reduced to six years if it can be demonstrated, on the basis of available evidence, that the original orphan medicinal product is sufficiently profitable not to justify maintenance of market exclusivity.

Defibrotide has been granted orphan drug designation by the EC for the treatment of VOD and prevention of GvHD until October 2023, by the Korean Ministry of Food and Drug

Safety to treat and prevent VOD, and by the Commonwealth of Australia-Department of Health for the treatment of VOD.

Vyxeos has been granted orphan drug designation by the EC until August 2028.

We also received Orphan Designation from EMA’s Committee for Orphan Medicinal Products, or COMP, for Epidyolex for DS, LGS and TSC, and the COMP reconfirmed the designation for DS, LGS and TSC upon EC’s approval.

The period of OME granted in relation to the original orphan medicinal product may, in addition, be reduced to six years if it can be demonstrated, on the basis of available evidence, that the original orphan medicinal product is sufficiently profitable not to justify maintenance of market exclusivity.

Defibrotide was granted orphan drug designation by the EC for the treatment of VOD and prevention of GvHD until October 2023, by the Korean Ministry of Food and Drug Safety to treat and prevent VOD, and by the Commonwealth of Australia-Department of Health for the treatment of VOD.

Vyxeos has been granted OME by the EC until August 2028.

Epidyolex has been granted OME for use as adjunct therapy of seizures associated with DS and LGS until September 2029, and for use as adjunctive therapy of seizures associated with TSC until April 2031.

Pharmaceutical Pricing, Reimbursement by Government and Private Payors and Patient Access

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Medicare Part B pays physicians who administer our products.

Under the Medicaid Drug Rebate Program, as a condition of having federal funds made available to the states for our drugs under Medicare Part B, we are required to pay a rebate to each state Medicaid program for our covered outpatient drugs that are dispensed to Medicaid beneficiaries and paid for by a state Medicaid program.

Medicaid rebates are based on pricing data we report on a monthly and quarterly basis to the U.S.

Centers for Medicare & Medicaid Services, or CMS, the federal agency that administers the Medicaid Drug Rebate Program and Medicare.

These data include the average manufacturer price and, in the case of innovator products, the best price for each drug which, in general, represents the lowest price available from the manufacturer to any entity in the U.S.

Under the Medicaid Drug Rebate Program, as a condition of having federal funds made available to the states for our drugs under Medicaid and Medicare Part B, we are required to pay a rebate to each state Medicaid program for our covered outpatient drugs that are dispensed to Medicaid beneficiaries and paid for by a state Medicaid program.

Medicaid rebates are based on pricing data we report on a monthly and quarterly basis to the CMS, the federal agency that administers Medicare and Medicaid, including the Medicaid Drug Rebate Program.

These data include the average manufacturer price and, in the case of innovator products, the best price

for each drug which, in general, represents the lowest price available from the manufacturer to any entity in the U.S.

in any pricing structure, calculated to include all applicable sales and associated rebates, discounts and other price concessions.

If we become aware that our reporting for a prior quarter was incorrect, or has changed as a result of recalculation of the pricing data, we are obligated to resubmit the corrected data for up to three years after those data originally were due.

We are required to provide average sales price, or ASP, information for certain of our products to CMS on a quarterly basis.

We are required to provide ASP information for certain of our products to CMS on a quarterly basis.

The ASP is calculated based on a statutorily defined formula as well as regulations and interpretations of the statute by CMS.

This information is used to compute Medicare payment rates, with rates for Medicare Part B drugs outside the hospital outpatient setting and in the hospital outpatient setting consisting of ASP plus a specified percentage.

Federal law requires that any company that participates in the Medicaid Drug Rebate Program also participate in the Public Health Service’s 340B program, or the 340B program, in order for federal funds to be available for the manufacturer’s drugs under Medicaid and Medicare Part B.

The 340B program, which is administered by the Health Resources and Services Administration, or HRSA, requires participating manufacturers to agree to charge statutorily defined covered entities no more than the 340B “ceiling price” for the manufacturer’s covered drugs used in an outpatient setting.

This information may be used to compute Medicare payment rates, with rates for Medicare Part B drugs outside the hospital outpatient setting and in the hospital outpatient setting consisting of ASP plus a specified percentage.

Federal law requires that any company that participates in the Medicaid Drug Rebate Program also participate in the 340B program, in order for federal funds to be available for the manufacturer’s drugs under Medicaid and Medicare Part B.

The 340B program, which is administered by the HRSA requires participating manufacturers to agree to charge statutorily defined covered entities no more than the 340B “ceiling price” for the manufacturer’s covered drugs used in an outpatient setting.

These 340B covered entities include certain qualifying community health clinics, a variety of entities that receive health services grants from the Public Health Service, and multiple categories of hospitals, including children’s hospitals, critical access hospitals, free standing cancer hospitals and hospitals that serve a disproportionate share of low-income patients.

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A provision in The American Rescue Plan Act of 2021 eliminated, effective January 2024, the statutory cap on rebates drug manufacturers are required to pay under the Medicaid Drug Rebate Program.

The elimination of the cap on rebates means

that manufacturer discounts to Medicaid may rise beginning in 2024 and, in certain circumstances, rebates could exceed the amount that state Medicaid programs pay for the drug.

The elimination of the cap on rebates means that manufacturer discounts to Medicaid may rise beginning in 2024 and, in certain circumstances, rebates could exceed the amount that state Medicaid programs pay for the drug.

This policy change will have the greatest impact on drugs whose prices have reached the 100 percent Average Manufacturer Price rebate cap.

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Effective January 2023, a provision of the Infrastructure Investment and Jobs Act requires a manufacturer of single source drugs or biologicals in single-use packages or single dose containers to pay a refund on discarded amounts of drug under Medicare Part B where the discarded amount exceeds an applicable threshold.

In order to be eligible to have our products paid for with federal funds under the Medicaid and Medicare Part B programs and purchased by certain federal agencies and grantees, we also participate in the U.S.

Department of Veterans Affairs, or VA, Federal Supply Schedule, or FSS, pricing program.

Under this program, we are obligated to make our products available for procurement on an FSS contract under which we must comply with standard government terms and conditions and charge a price to certain federal agencies that is no higher than the statutory Federal Ceiling Price, or FCP.

The FCP is based on the non-federal average manufacturer price, or Non-FAMP, which we calculate and report to the VA on a quarterly and annual basis.

We also participate in the Tricare Retail Pharmacy program, under which we pay quarterly rebates on utilization of innovator products that are dispensed through the Tricare Retail Pharmacy network to Tricare beneficiaries.

The FCP is based on the Non-FAMP, which we calculate and report to the VA on a quarterly and annual basis.

We also participate in the Tricare program, under which we pay quarterly rebates on utilization of innovator products that are dispensed through the Tricare Retail Pharmacy network to Tricare beneficiaries.

The rebates are calculated as the difference between the annual Non-FAMP and FCP.

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For example, in 2017, California adopted a prescription drug price transparency state bill requiring advance notice of and an explanation for price increases of certain drugs that exceed a specified threshold.

Similar bills have been previously introduced at the federal level and additional legislation could be introduced this year.

Additionally, some individual states have begun establishing Prescription Drug Affordability Boards to review high-cost drugs and, in some cases, set upper payment limits.

Similar bills have been previously introduced at the federal level and additional legislation could be introduced in the near future.

Similar to what is occurring in the U.S., political, economic and regulatory developments outside of the U.S.

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In various EU member states, we expect to be subject to continuous cost-cutting measures, such as voluntary and temporary sales rebates, lower maximum prices, lower or lack of reimbursement coverage and incentives to use cheaper, usually generic, products as an alternative.

Health technology assessment, or HTA, of medicinal products is becoming an increasingly common part of the pricing and reimbursement procedures in some EU member states, including countries representing major markets.

HTA of medicinal products is becoming an increasingly common part of the pricing and reimbursement procedures in some EU member states, including countries representing major markets.

The HTA process, which is governed by the national laws of these countries, is the procedure according to which the assessment of the public health impact, therapeutic impact and the economic and societal impact of use of a given medicinal product in the national healthcare systems of the individual country is conducted.

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In December 2021, the EC adopted a HTA regulation intended to boost cooperation among EU member states in assessing health technologies, including new medicinal products.

The regulation will apply to all EU member states from January 2025 provides that EU member states will be able to use common HTA tools, methodologies, and procedures across the EU.

Individual EU member states will continue to be responsible for drawing conclusions on the overall value of a new health technology for their healthcare system, and pricing and reimbursement decisions.

The HTA regulation entered into application in January 2025 and provides that EU member states must use common HTA tools, methodologies, and procedures across the EU.

However, individual EU member states continue to be responsible for drawing conclusions on the overall value of a new health technology for their healthcare system, and pricing and reimbursement decisions.

In the EU, our products are marketed through various channels and within different legal frameworks.

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Such reimbursement may no longer be available if authorization for named patient or compassionate use programs expire or is terminated or if marketing authorization is granted for the product.

In some EU member states, authorization and reimbursement policies may also delay commercialization of our products, or

may adversely affect our ability to sell our products on a profitable basis.

In some EU member states, authorization and reimbursement policies may also delay commercialization of our products, or may adversely affect our ability to sell our products on a profitable basis.

After initial price and reimbursement approvals, reductions in prices and changes in reimbursement levels can be triggered by multiple factors, including reference pricing systems and publication of discounts by third party payors or authorities in other countries.

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Attorney’s Office for the District of Massachusetts requesting documents related to our support of charitable organizations that provide financial assistance to Medicare patients.

In April 2019, we finalized our civil settlement agreement with the DOJ and OIG, and entered into a corporate integrity agreement requiring us to maintain our ongoing corporate compliance program and obligating us to implement or continue, as applicable, a set of defined corporate integrity activities to ensure compliance with OIG’s policies around charitable contributions for a period of five years from the effective date of the corporate integrity agreement.

implement or continue, as applicable, a set of defined corporate integrity activities to ensure compliance with OIG’s policies around charitable contributions for a period of five years from the effective date of the corporate integrity agreement.

As of August 2024, we have fulfilled the terms and OIG closed out our corporate integrity agreement.

About Jazz Pharmaceuticals plc

Jazz Pharmaceuticals plc was formed under the laws of Ireland (registered number 399192) as a private limited liability company in March 2005 under the name Azur Pharma Limited and was subsequently re-registered as a public limited company under the name Azur Pharma Public Limited Company, or Azur Pharma, in October 2011.

On January 18, 2012, the businesses of Jazz Pharmaceuticals, Inc.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business