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Item 1. Business

2026-02-24 compared with 2025-02-26 · 417 added, 355 removed, 693 unchanged (53% of the section changed)

Jazz Pharmaceuticals plc is a global biopharmaceutical company whose purpose is to innovate to transform the lives of patients and their families.

We are dedicated to developing life-changing medicines for people with serious diseases - often with limited or no therapeutic options.

We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments.

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 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 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.

We are dedicated to developing life-changing medicines for people with rare disease – often with limited or no therapeutic options.

We have a diverse portfolio of medicines, including leading therapies addressing epilepsies, cancers and sleep disorders.

Our patient-focused and science-driven approach powers pioneering R&D advancements across our robust pipeline of innovative therapeutics.

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

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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.

• 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 (IHC3+) BTC, as detected by an FDA-approved test.

In June 2025, the EC granted conditional marketing authorization for Ziihera for the treatment of adults with unresectable locally advanced or metastatic HER2-positive (IHC3+) BTC previously treated with at least one prior line of systemic therapy.

In January 2026, Ziihera obtained conditional approval in Canada for the treatment of adults with previously treated, unresectable locally advanced or metastatic HER2-positive (IHC3+) BTC, as monotherapy.

• Modeyso™ (dordaviprone) , a product approved by FDA in August 2025 under FDA's accelerated approval pathway for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.

• 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 SCLC with disease progression on or after platinum-based chemotherapy;

approved by FDA in October 2025 in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs as a first-line maintenance treatment for adults with extensive-stage SCLC whose disease has not progressed after first-line induction therapy with atezolizumab, carboplatin and etoposide;

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

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

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coli -derived asparaginase.

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 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.

For a summary of our ongoing research and development activities, see “Business—Research and Development” in this Part I, Item 1.

In September 2023, the EC granted marketing authorization under the trade name Enrylaze ® .

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

We continue to invest in pipeline programs that further our rare disease strategy.

For a summary of our ongoing R&D activities, see “Business—Research and Development Progress” in this Part I, Item 1.

We focus on rare diseases, which often have high unmet needs and small patient populations, resulting in efficient, concentrated call points.

We seek to identify and develop highly 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.

Our strategy to deliver sustainable growth and enhanced value continues to be focused on:

• Strong commercial execution to drive diversified revenue growth and address unmet medical needs of our patients who often have limited or no therapeutic options;

• Expanding and advancing our pipeline to achieve a valuable portfolio of durable, highly differentiated products;

• Building an efficient and productive development engine to identify and progress early-, mid- and late-stage assets;

• Identifying and acquiring novel product candidates and approved therapies to complement our existing pipeline and commercial portfolio;

• Investing in an efficient, scalable operating model and differentiated capabilities to enable growth;

• Unlocking further value through indication expansion and entry into global markets.

Our Commercialized Products

Our Sleep Products .

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.

Our Rare Sleep Products .

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

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.

In August 2021, Xywav became the first and only therapy approved by FDA for the treatment of IH in adults.

Xywav is an oxybate therapy that contains 92% less sodium than Xyrem.

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

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When patients transition from Xyrem to Xywav, Xywav treatment is initiated at the same dose and regimen (gram for gram) and titrated as needed based on efficacy and tolerability.

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 ODE for Xywav in narcolepsy through July 21, 2027 (which was subsequently extended to January 21, 2028).

We view the continued 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 ODE for Xywav in EDS and cataplexy 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.

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Lumryz has the same sodium content as Xyrem.

Xywav is the only approved oxybate therapy that does not carry a warning and precaution related to high sodium intake.

Our first medicine in rare sleep disorders was Xyrem, which contains 1640mg of sodium per 9-gram dose per night.

Xyrem is indicated for the treatment of cataplexy and EDS in patients seven years of age and older with narcolepsy.

Xywav contains 92% less sodium than Xyrem and is the only approved oxybate therapy that does not carry a warning and precaution related to high sodium intake.

On August 12, 2021, FDA approved Xywav for the treatment of IH in adults.

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In January 2022, FDA recognized seven years of ODE for Xywav in IH through August 12, 2028.

IH is a debilitating neurologic sleep disorder characterized by chronic EDS (the inability to stay awake and alert during the day resulting in the irrepressible need to sleep or unplanned lapses into sleep or drowsiness), severe sleep inertia, and prolonged and

non-restorative nighttime sleep.

Although there are overlapping clinical features with other conditions, including narcolepsy, IH has its own specific diagnostic criteria.

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We have seen strong adoption of Xywav in narcolepsy since its launch in November 2020 and increasing adoption in IH since its launch in November 2021.

At the end of 2025, there were approximately 16,175 patients taking Xywav, including approximately 10,950 patients with narcolepsy and approximately 5,225 patients with IH.

In 2025, net product sales of Xywav were $1,657.0 million, which represented 41% of our total net product sales for the year.

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for the treatment of cataplexy or EDS in pediatric patients seven years of age and older with narcolepsy.

As of January 2026, we are aware of two high-sodium oxybate generics of Xyrem that have been launched.

In 2025, net product sales of Xyrem were $146.0 million, which represented 4% of our total net product sales for the year.

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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 GW Acquisition, which expanded our growing neuroscience business with a global, high-growth childhood-onset epilepsy franchise.

Our current agreements with ESSDS were amended in November 2025 to extend the term of the central pharmacy agreement to December 31, 2026, and the patient support services agreement to September 1, 2026.

The agreements may be terminated by either party at any time without cause on 180 days’ prior written notice to the other party.

Our Rare Epilepsy Product

We acquired Epidiolex (Epidyolex outside the U.S.) in May 2021 as part of our GW Acquisition, which added a durable and long-lived asset in rare epilepsies to our portfolio.

Epidiolex was approved in the U.S.

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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:

United Kingdom, Germany, Italy, Spain and France.

The clobazam restriction is limited to the EU and Great Britain .

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.

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.

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.

Epidyolex is now launched and reimbursed in more than 40 countries.

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

LGS and DS are severe childhood-onset, drug-resistant epilepsy syndromes.

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TSC affects approximately 50,000 individuals in the U.S.

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

Epidiolex has received ODE to treat seizures associated with TSC, which expires in July 2027.

From October 2023 through January 2025, we entered into settlement agreements with each of the Epidiolex ANDA Filers that resolved our patent litigation with them related to Epidiolex.

Under the settlement agreements, we granted each of the Epidiolex ANDA Filers a license to manufacture, market, and sell its own generic version of Epidiolex beginning in the very late 2030s, or earlier under certain circumstances, including but not limited to the launch of another generic Epidiolex product or a final decision that all unexpired claims of the Epidiolex patents are not infringed, or are invalid and/or unenforceable.

Net product sales of Epidiolex/Epidyolex in 2025 were $1,059.2 million , w hich represented 26% of our total net product sales for the year.

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.

Rylaze is the only recombinant Erwinia asparaginase manufactured product that maintains a clinically meaningful level of serum asparaginase activity throughout the entire intended course of treatment.

We developed Rylaze to address the needs of patients and health care providers for an innovative, high-quality Erwinia asparaginase with reliable supply.

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

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.

Our Rare Oncology Products

We acquired our exclusive development and commercialization rights to Ziihera in 2022 through an exclusive licensing and collaboration 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 was granted accelerated approval by FDA in November 2024 and is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC3+) BTC, as detected by an FDA-approved test.

Ziihera was launched in December 2024.

Continued approval for BTC may be contingent upon verification and description of clinical benefit in the Phase 3 HERIZON-BTC-302 confirmatory trial.

In 2025, net product sales of Ziihera were $24.8 million, which represented less than 1% of our total net product sales for the year.

We completed the Chimerix Acquisition in April 2025 for a total of cash consideration of $944.2 million, adding Modeyso (dordaviprone), a protease activator of the mitochondrial ClpP that also inhibits DRD2, to our rare oncology portfolio.

In August 2025, Modeyso was granted accelerated approval by FDA for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.

Modeyso is the first and only treatment option approved by FDA for this ultra-rare and aggressive brain tumor that mainly affects children and young adults.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in the Phase 3 ACTION confirmatory trial.

In connection with the approval by FDA of Modeyso in August 2025, we received a rare pediatric disease PRV, which we sold in January 2026 for total cash consideration of $200.0 million of which 50% is attributable to us.

Net product sales of Modeyso in 2025 were $48.0 million , w hich represented 1% of our total net product sales for the year.

We acquired U.S.

development and commercialization rights to Zepzelca in early 2020, and launched six months thereafter, with an indication for treatment of patients with SCLC with disease progression on or after platinum-based chemotherapy.

development and commercialization rights to Zepzelca in early 2020, and launched six months thereafter, with an indication for treatment of patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy.

Zepzelca is an alkylating drug that binds guanine residues within DNA.

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Our education and promotional efforts are focused on SCLC-treating physicians.

We are continuing to raise awareness of Zepzelca across academic and community cancer centers.

We are continuing to market Zepzelca across academic and community cancer centers.

Our exclusive U.S.

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

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 October 2024, we announced positive top-line results from the Phase 3 IMforte trial showing a statistically significant and clinically meaningful progression-free survival and overall survival benefit for Zepzelca and atezolizumab in combination in the first-line maintenance setting.

In June 2025, the sNDA submission for the combination of Zepzelca with atezolizumab or atezolizumab and hyaluronidase-tqjs was granted priority review by FDA and subsequently approved in October 2025 as a first-line maintenance treatment for adults with extensive-stage SCLC whose disease has not progressed after first-line induction therapy with atezolizumab, or atezolizumab and hyaluronidase-tqjs carboplatin and etoposide.

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 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 2025, net product sales of Zepzelca were $307.3 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.

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.

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 patients with ALL, and LBL, in pediatric and adult patients one month and older who have developed hypersensitivity to E.

coli-derived asparaginase.

Rylaze is the only recombinant erwinia asparaginase manufactured product that maintains a clinically meaningful level of serum asparaginase activity throughout the entire intended course of treatment.

We developed Rylaze to address the needs of patients and health care providers for an innovative, high-quality erwinia asparaginase with reliable supply.

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 also approved in Canada, Switzerland and Australia.

In 2025, net product sales of Rylaze were $402.9 million, which represented 10% 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.

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 through a combination of launching internally developed therapies and commercial assets or investigational therapies acquired through corporate development.

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

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

June 2018 U.S.

June 2018 and July 2020 U.S.

Adjunctive therapy of seizures associated with LGS, DS, or TSC in patients 1 year of age and older.

April and October 2021 Israel

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

November 2023 Canada

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

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

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

April 2021 EU, Great Britain, Israel and Switzerland

Epidiolex® (cannabidiol) For adjunctive therapy of seizures associated with LGS, DS or TSC for patients 2 years of age and older.

November 2023 Canada

April 2021 EU, Great Britain, EEA and Switzerland

Ziihera® (zanidatamab-hrii) Treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC3+) BTC, as detected by an FDA-approved test.

November 2024 U.S.

(licensed from Zymeworks) 2

Treatment of adults with unresectable locally advanced or metastatic HER2-positive (IHC3+) BTC previously treated with at least one prior line of systemic therapy.

June 2025 EU (licensed from Zymeworks) 3

Treatment of adults with previously treated, unresectable locally advanced or metastatic HER2-positive (IHC3+) BTC, as monotherapy.

January 2026 Canada (licensed from Zymeworks) 4

Modeyso™ (dordaviprone) Treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.

August 2025 U.S.

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

June 2020 U.S.

(licensed from PharmaMar) 2

Treatment of adults with Stage III or metastatic SCLC who have progressed on or after platinum-containing therapy.

September 2021 Canada (licensed from PharmaMar) 4

In combination with atezolizumab or atezolizumab and hyaluronidase-tqjs for the first-line maintenance treatment of adult patients with extensive-stage SCLC whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin and etoposide.

October 2025 U.S.

(licensed from PharmaMar)

Rylaze® (asparaginase erwinia chrysanthemi (recombinant)-

rywn) A component of a multi-agent chemotherapeutic regimen for the treatment of ALL or LBL in adult and pediatric patients 1 month or older who have developed hypersensitivity to E.

rywn) A component of a multi-agent chemotherapeutic regimen for the treatment of ALL, and LBL, in adult and pediatric patients 1 month or older who have developed hypersensitivity to E.

coli-derived asparaginase.

June 2021 U.S.

Rylaze® (crisantaspase recombinant) A component of a multi-agent chemotherapeutic regimen for the treatment of ALL and LBL, in adults and pediatric patients 1 year or older who have developed hypersensitivity to

coli-derived asparaginase.

3 unchanged sentences

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.

June 2020 U.S.

(licensed from PharmaMar) 2

Treatment of adults with Stage III or metastatic SCLC who have progressed on or after platinum-containing therapy.

September 2021 Canada (licensed from PharmaMar) 3

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

2 Accelerated approval received from FDA

3 Conditional marketing authorization granted by EC

4 Conditional approval received from Health Canada

Research and Development Progress

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 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 in precision oncology, as well as in neuroscience.

Our R&D 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 and early-stage programs for novel therapies that further our rare disease strategy and leverage the strong R&D capabilities we have built.

We are increasingly leveraging our internal R&D function, and we have entered into collaborations with third parties for the R&D 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 areas where we have deep expertise with a focus on validated targets and mechanisms.

Zanidatamab .

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

Following positive data from a pivotal Phase 2 clinical trial evaluating zanidatamab monotherapy in patients with previously treated advanced or metastatic HER2-amplified BTC, we completed a BLA submission in second-line BTC in March 2024.

In May 2024, FDA granted priority review of the BLA;

we received FDA accelerated approval for this BLA in November 2024.

In April 2025, we announced that CHMP adopted a positive opinion recommending the conditional marketing authorization of zanidatamab in second-line BTC.

In November 2025, we announced positive top-line results from the pivotal Phase 3 HERIZON-GEA-01 trial of zanidatamab in combination with chemotherapy, with or without tislelizumab, as first-line treatment for adults with HER2-positive locally advanced or metastatic GEA.

In January 2026, we presented late-breaking results from the trial at ASCO GI.

The investigational arm containing zanidatamab plus tislelizumab and chemotherapy demonstrated a statistically significant and clinically meaningful overall survival benefit of more than two years of median overall survival.

The greater than seven-month improvement in median overall survival represents a 28% reduction in the risk of death versus the control arm.

Both investigational arms led to a statistically significant and clinically meaningful median progression-free survival of more than one year, representing a greater than four-month improvement and 35% reduction in the risk of disease progression or death versus the control arm.

FDA granted BTD for zanidatamab's development for patients with HER2+ unresectable locally advanced or metastatic GEA.

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

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.

a Phase 2 DiscovHER-Pan-206 trial evaluating zanidatamab monotherapy in previously-treated patients with various HER2-positive (IHC3+) cancers, a Phase 2 EmpowHER-BC-208 trial to evaluate zanidatamab in patients with HER2-positive neoadjuvant and adjuvant breast cancer, a Phase 3 trial EmpowHER-303 to evaluate zanidatamab plus chemotherapy or trastuzumab plus chemotherapy in patients with HER2-positive breast cancer whose disease has progressed on previous T-DXd treatment, and a Phase 3 confirmatory trial examining zanidatamab in first-line patients with HER2-positive BTC.

Our development plan for Zepzelca continues to progress.

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 October 2024, we announced positive top-line results from the Phase 3 IMforte trial showing a statistically significant and clinically meaningful benefit for Zepzelca and atezolizumab in combination in the first-line maintenance setting.

In April 2025, we announced the submission of an sNDA to support this combination in the first-line maintenance setting.

In June 2025, FDA granted priority review of the sNDA and we subsequently received FDA approval in October 2025 for the combination as a first-line maintenance treatment of adult patients with extensive-stage SCLC whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin and etoposide.

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.

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.

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

Updated results from the Phase 4 observational trial were presented at the 2025 WCLC that showed Zepzelca demonstrated clinically meaningful effectiveness across subgroups, including those with platinum-resistant disease and those with CNS metastases.

The safety and tolerability profile observed in this Phase 4 study was consistent with prior findings, with no new safety signals reported.

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.

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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.

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 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 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:

We have an ongoing Phase 1b study of Epidiolex for the treatment of focal-onset seizures.

The study will assess the efficacy of Epidiolex as an adjunctive treatment in reducing the frequency of focal seizures compared to baseline as well as the effect of Epidiolex on health outcome endpoints in early line and refractory participants with focal-onset seizures.

Through third parties, we are also pursuing preclinical and clinical R&D activities under a number of licensing and collaboration agreements, including with:

• 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;

• Redx for preclinical collaboration activities related to G12D selective and pan-KRAS molecules that we purchased from Redx;

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

• Saniona to develop a small molecule activator of Kv7.2/Kv7.3 potassium channels for epilepsy and other potential indications;

• We are also evaluating the use of our CombiPlex platform in a number of therapeutic formulations and combinations in oncology as part of our internal oncology R&D activities.

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

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 (COG cooperative group study) (ongoing trial)

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

Zanidatamab First-line HER2-positive GEA (HERIZON-GEA-01) (ongoing trial)

First-line HER2-positive BTC (HERIZON-BTC-302) (ongoing confirmatory trial)

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

Dordaviprone First-line H3 K27M-mutant diffuse glioma (ACTION trial) (ongoing confirmatory trial)

Vyxeos Newly diagnosed adults with standard- and high-risk AML (AMLSG 30-18) (cooperative group study) (ongoing trial)

Newly diagnosed pediatric patients with AML (AAML 1831) (COG cooperative group study) (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 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)

Neoadjuvant and adjuvant breast cancer (EmpowHER-BC-208) (ongoing trial)

HER2+ advanced GEA in combination with paclitaxel and ramucirumab (Canadian Cancer Trials Group collaboration) (ongoing trial)

HER2+/PD-L1+ mGEA in combination with pembrolizumab and chemotherapy (ZANGEA) (collaboration study) (trial enrolling)

Early stage HER2/neu positive (HER2+) breast cancer (collaboration study) (ongoing trial)

Vyxeos High-risk MDS (PALOMA) (cooperative group study) (ongoing trial)

Newly diagnosed untreated patients with high-risk AML (MyeloMATCH Tier SWOG) (cooperative group study) (ongoing trial)

De novo intermediate or adverse risk AML stratified by genomics (ALFA2101) (collaboration study) (ongoing trial)

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

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

Zanidatamab Previously treated HER2+ HR+ breast cancer in combination with palbociclib (ongoing trial)

Zanidatamab First-line breast cancer and GEA (BeiGene trial) (ongoing trial)

Zanidatamab HER2-expressing breast cancer in combination with ALX148 (ongoing trial)

AML or high-risk MDS that has IDH1 mutation (MD Anderson collaboration study) (ongoing trial)

Pheochromocytoma and paraganglioma (acquired from Chimerix) (ongoing trial)

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

Primary central nervous system tumors (acquired from Chimerix) (ongoing trial)

Newly diagnosed or recurrent diffuse midline gliomas and other recurrent primary malignant CNS tumors (UCSF collaboration) (acquired from Chimerix) (ongoing trial)

Epidiolex Focal-onset seizures

JZP047 Absence epilepsy

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

Undisclosed targets Oncology

Hematology/oncology exploratory activities

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

JZP324 Oxybate extended-release formulation (planned trial)

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

CombiPlex® Hematology/oncology exploratory activities

Undisclosed targets Sleep

Other Neuroscience

*Also known as DSP-0187 (see discussion above in this section for JZP441)

1 Also known as ONC206

2 Also known as ONC212

3 Also known as SAN2355

Commercialization Activities

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, 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.

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, Ziihera, Modeyso, Zepzelca, Rylaze, 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, 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.

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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 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.

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

In addition, we directly market Xywav, Zepzelca 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, 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.

We promote Ziihera, Modeyso, 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.

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.

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.

We are committed to creating a high performing organization grounded in purpose, defined by disciplined execution, and united by our mission to innovate to transform the lives of patients.

Our goals are clear:

(1) create a purpose-driven, people-centric, and exceptional place to work, and (2) live our core values of Integrity, Collaboration, Passion, Innovation, and Pursuit of Excellence in everything we do.

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.

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

As of December 31, 2025, Jazz employed approximately 2,890 people worldwide, with approximately 53% in the U.S.

and approximately 47% outside the U.S., primarily in the U.K., Ireland and across the EU.

More than 740 employees – approximately 26% of our workforce – support our R&D activities, reflecting our continued investment in scientific excellence and innovation.

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.

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).

• In the U.S., people of color represent 35% of our U.S.

workforce and 20% at the leadership level.

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.

Our culture is rooted in purpose to make an impact on patients’ lives, shaped by deep scientific expertise and defined by disciplined execution.

We bring a rare-disease mindset to our work – moving with urgency, clarity, and accountability.

By fostering a people-centric and performance driven environment, we aim to create a workplace where purpose fuels passion and accountability drives results.

At Jazz, our people and culture are central to driving innovation, performance, and long-term growth – we aim to foster a workplace where employees feel supported, connected, and empowered to deliver their best work.

We strive to create an environment where employees live our values, bring bold ideas forward, and operate with clarity and focus.

We are committed to fostering an inclusive culture where all employees feel they belong – a culture that reflects the diverse perspectives of the patients and communities we serve and strengthens our ability to innovate and compete.

Our belonging and inclusion strategy focuses on:

(1) cultivating a workforce that reflects unique backgrounds, experiences, and talents (2) investing in and ensuring equal opportunities for our talent to develop;

and (3) building a culture where inclusion and belonging are core to how we work.

We believe in a workforce and culture that fosters belonging and inclusion, and strengthens innovation, engagement, and performance.

Our employee resource groups are open to all employees and include three ConcERTos, and six Affinity Forums.

They provide platform engagement, education and community involvement.

As of the end of 2025, 38% of our global workforce participated in at least one of these groups.

While we are proud of our progress, we remain committed to building an inclusive, high-performing workplace that supports employees of all backgrounds, including within 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 and their families.

We believe employee engagement and the power of our employee voices is foundational to employee belonging and 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 employee feedback surveys.

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 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 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.

Growth, Development and Total Rewards .

Our talent strategy focuses on attracting the best talent, recognizing and rewarding the performance of our employees as defined by both what they accomplished and how they accomplished it, and continually developing our talent through new experiences and learning opportunities.

We believe there is ample opportunity for growth and development at Jazz and there is not a one size fits all approach to growing our talent.

We strive to create the best career experience for all of our employees and encourage them to have regular dialogue with their leadership to create meaningful career development plans.

Our performance management process supports our culture of continual feedback and coaching, and ongoing growth and development through new experiences and learning.

We encourage all employees to have an individual development plan to outline learning and growth interests and focus areas.

We leverage digital learning platforms to provide on demand, bite-sized learning to all employees that can be accessed 24/7 on a range of topics from leadership, personal effectiveness and well-being.

In addition, we provide a number of self-service learning resources via our intranet site on topics such as High-Performance Teamwork, Decision Making, Hybrid Working, and Digital Skills development.

We continue to offer tuition reimbursement in our major markets aimed at growth and career development.

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 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 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 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 believe employee engagement and the power of employee voice is foundational to belonging and strong performance.

Our teams are motivated by the opportunity to deliver meaningful impact for patients and are supported by a culture that values clarity, accountability, and scientific rigor.

We maintain transparent and regular communication channels – including all-employee meetings, leadership messages, town halls, top leadership forums, pulse checks, and employee feedback surveys.

Our surveys consistently achieve participation rates above 75% and reflect strong engagement, including connection to purpose, sense of belonging, and confidence in Jazz as a great place to work.

We continue to strengthen high-performance practices such as decision-making discipline, planning and prioritizing work, constructive challenge, accountability, and a growth mindset.

Survey insights inform programs and activities that support our strategic priorities and our goal of building an agile, scalable operating culture.

Community Beat ConcERTo plays a key role in strengthening culture and belonging through local engagement activities that connect employees to our strategy, support communities, and promote well-being.

They help foster connection across our hybrid working model by engaging remote employees and maximizing meaningful time together at our sites and offices.

Capabilities and Talent – Growth, Development and Total Rewards .

As we enter our next chapter, we are strengthening the capabilities and culture that support our long-term growth ambition – expanding our rare-disease portfolio, executing with discipline, and building durable franchises that deliver meaningful value for patients and shareholders.

We invest in the specialized scientific, clinical, and commercial capabilities that differentiate Jazz in rare disease and strengthen our right to win.

Our talent strategy focuses on building and sustaining the capabilities required to advance our rare disease portfolio and deliver a disciplined approach to drive innovation.

We believe our people are the foundation of our future.

Their expertise, resilience, and commitment to patients enable us to advance our strategy with focus and confidence.

We aim to attract exceptional talent, recognize and reward high performance, and continually develop our people through meaningful experiences and learning opportunities.

We maintain a strong focus on capability development and succession planning for critical roles.

We regularly review talent development and succession plans across functions to support business continuity and develop a strong pipeline of future leaders.

We encourage our employees to engage in regular dialogue with their leaders to create development plans aligned to their aspirations and business needs.

Our performance management process reinforces continual feedback, coaching, and growth through new experiences and learning.

We encourage all employees to maintain an individual development plan outlining learning interests and focus areas.

We continue to sharpen the capabilities that fuel our performance – investing in capability development in key areas such as patient insights and evidence generation, clinical development excellence, AI-enabled tools, and customer experience platforms that support long-term success.

Broadly across the organization, we leverage digital learning platforms to provide on demand learning across leadership, personal effectiveness, and well-being.

We also offer self-service learning resources on topics such as high-performance teamwork, decision-making, hybrid working, and digital skills.

Tuition reimbursement is available in our major markets to support career development.

We have strengthened our operating discipline through clearer enterprise priorities, aligned quarterly expectations, and cross functional ways of working that support consistent high-quality execution.

In 2025, we continued to focus on the capabilities of our Global Leadership Team (Top 80 leaders) to strengthen leadership excellence and cross functional collaboration in pursuit of our enterprise strategic goals.

We focused on a broader leadership group of people managers in 2025 to strengthen leadership behaviors linked to a high-performance culture, including constructive challenge, accountability, and enterprise-wide alignment to our goals.

We provide our employees with competitive and locally relevant compensation and benefits that support our overarching strategy to attract, retain and reward highly talented employees.

This includes (1) 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 (2) participation in our long-term equity incentive plans, which fosters an ownership culture and (3) benefits that support employee well-being.

We are committed to building and maintaining a culture of health and wellbeing.

We support employees and their families through programs that inspire them to focus mental and emotional health, physical well-being, financial wellness, 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 an enhanced suite of global paid leave and other time-off policies 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.

• In 2026, we will hold our second-ever Jazz Wellbeing Week, providing dedicated time off for 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;

and increased investment in resources focused on inclusion and belonging.

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

We strive to enable our employees to live our values and support one another while delivering on our patient mission.

Leader expectations and tools are essential as employee needs evolve – including flexibility, whole-person support, and productive work environments.

We provide productivity and collaboration tools and resources for remote work, training and tools for leaders managing distributed teams, flexibility within work schedules and leave programs, expanded employees assistance and mindfulness programs, and increased investment in resources focused on inclusion and belonging.

Through direct input from employees, external insights and best practices, we developed our flexible working model;

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Our manufacturing activities involve the controlled storage, use and disposal of chemicals and solvents.

Environmental and health and safety authorities in Ireland, the U.K.

and Italy administer laws governing, among other matters, the emission of pollutants into the air (including the workplace), the discharge of pollutants into bodies of water, the storage, use, handling and disposal of hazardous substances, the exposure of persons to hazardous substances, and the general health, safety and welfare of employees and members of the public.

Environmental and health and safety authorities administer laws governing, among other matters, the emission and discharge of pollutants, hazardous substances, workplace exposure, and employee and public welfare.

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.

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We seek to operate our manufacturing facilities in an environmentally responsible way to protect our people, our business, our environment and the local communities in which we operate.

In light of the potential impact of our business on the environment, we have adopted a number of internal environmental policies and management systems designed to manage our operations in compliance with applicable laws, directives and regulations on environmental protection and in support of environmental sustainability and local biodiversity.

Our environmental policies and management systems include procedures for assessing compliance with applicable environmental laws and regulations and reporting incidents of non-compliance to applicable governmental authorities.

We have adopted internal environmental policies and management systems designed to support compliance with applicable laws, directives and regulations on environmental protection and in support of environmental sustainability and local biodiversity.

These include procedures for assessing compliance with applicable environmental laws and regulations and reporting incidents of non-compliance to applicable governmental authorities.

For example, we have environmental policies governing our manufacturing facilities in Ireland, the U.K.

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for the treatment of both cataplexy and EDS in both adult and pediatric patients with narcolepsy.

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 Avadel’s Lumryz, a branded product for treatment of cataplexy and/or EDS in narcolepsy.

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

Xywav and Xyrem face competition from Alkermes’ Lumryz (acquired through its acquisition of Avadel), 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.

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.

market in June 2023, as well as potential future competition from generic versions of high-sodium oxybate , including a generic version of high-sodium oxybate from Amneal approved in September 2025 and from Ascent approved in November 2025.

We and Avadel were engaged in various litigation regarding Lumryz and our oxybate products, which was settled in September 2025.

For additional information on litigation and the related settlement 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 from July 2023 through the end of 2025, 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.

We have the right to receive a meaningful royalty from Hikma on net sales of the Hikma AG product;

the royalty rate was fixed for the second half of 2023.

There was also a substantial increase in the royalty rate beginning in January 2024, which will remain fixed for the duration of the agreement's term.

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

In September, 2023, Hikma had elected to continue to sell the Hikma AG product, with royalties to be paid to us, for an additional four years beginning in January 2024.

Pursuant to amendments to our AG agreement with Hikma, effective January 1, 2026, we extended the period during which Hikma is permitted to sell the Hikma AG product until December 31, 2029.

Either we or Hikma may provide notice of intent to terminate the amended agreement as early as October 1, 2026, in accordance with notice provisions in the agreement.

Under these amendments, we continue to have the right to a meaningful royalty from Hikma on net sales of the Hikma AG product throughout the extended Hikma AG period, which royalty rate was fixed through the end of 2025 and then subject to specified reductions as set forth in our agreement with Hikma.

We are also paid for supply of the Hikma AG product and are reimbursed by Hikma for a portion of the services costs associated with the operation of the Xywav and Xyrem REMS, and distribution of the Hikma AG product.

Hikma also maintains a license to launch its own generic sodium oxybate product, but, if it elects to launch its own generic product, Hikma will no longer have the right to sell the Hikma AG product.

In addition, Hikma would need to set up its own REMS (or join an existing REMS operated by another company), which must be open to any other company seeking to commercialize a sodium oxybate product.

Amneal also had rights to sell a low-single-digit percentage of historical Xyrem sales over each 6-month sales period, which terminated at the end of 2025.

In September 2025, Amneal received FDA approval for a generic version of high-sodium oxybate.

In addition, in November 2025, Ascent received FDA approval for a generic version of high-sodium oxybate.

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.

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Also, in the future we expect competition from generic versions of sodium oxybate.

For example, we received notices in June 2021 and February 2023, that Lupin and Teva, respectively, filed ANDAs for generic versions of Xywav.

For example, we received notices in June 2021, February 2023 and July 2025, that Lupin, Teva and Granules, respectively, filed ANDAs for generic versions of Xywav.

Furthermore, in January 2026, we received notices from Tris Pharma that it had filed with FDA a Section 505(b)(2) NDA for generic versions of Xyrem and Xywav.

On October 13, 2023, Lupin announced that it has received tentative approval for its application to market a generic version of Xywav.

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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, Alkermes acquired Avadel in February 2026, which may strengthen both companies and

we may experience increased competition from the combined company.

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 R&D on orexin 2 receptor agonists for the treatment of sleep disorders, including narcolepsy and IH, which companies include Takeda, Merck & Co., Inc., Eisai Co., Ltd., Centessa Pharmaceuticals plc and Alkermes.

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.

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

Ovid Therapeutics Inc./Takeda, Eisai Company Limited, Praxis Precision Medicines, Inc., Bright Minds Biosciences Inc., H Lundbeck A/S and others 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.

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With respect to the marketing of CBD as a food or dietary supplement, in January 2023, FDA concluded that the existing regulatory frameworks for foods and supplements were not appropriate for CBD products and denied three citizen petitions that had asked the agency to conduct rulemaking to allow the marketing of CBD products as dietary supplements.

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

In addition, U.S.

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 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.

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In January 2023, we filed patent infringement suits against these ANDA filers.

For a description of this litigation, see “ Epidiolex 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.

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, which was approved for use in the U.S.

From October 2023 through January 2025, we entered into settlement agreements with each of the Epidiolex ANDA Filers that resolved our patent litigation with them related to Epidiolex.

Zepzelca faces competition from topotecan and tarlatamab, which are approved treatments 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 for the treatment of first and second line SCLC in various phases of development, including Amgen Inc.’s tarlatamab, which was approved for second line 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 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.

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

In September 2025, we filed an additional lawsuit against each of the Zepzelca ANDA Filers, alleging that, by filing its ANDA, each party infringed the newly-issued patent related to a method of treatment using Zepzelca.

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.

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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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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.

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.

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

In December 2024, FDA accepted an ANDA for a generic version of Defitelio.

In March 2025, we received a notice from Almaject that it had filed with FDA an ANDA for a generic version of Defitelio.

In April 2025, we filed a patent infringement lawsuit against Almaject.

For a description of this litigation, see “ Defitelio 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 this lawsuit, we expect that a stay of approval of up to 30 months will be imposed by FDA on Almaject’s ANDA.

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

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In the U.S., Xywav and Xyrem are sold to one certified specialty pharmacy, ESSDS, that ships Xywav and Xyrem directly to patients.

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

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

Modeyso is sold to one certified specialty pharmacy, Onco360, that ships Modeyso directly to patients.

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.

Zepzelca, Rylaze, Ziihera and Vyxeos 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.

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In countries where there is no marketing authorization, Epidyolex is available pursuant to named patient programs, temporary use authorizations or similar authorizations in accordance with local regulations controlling the medical use of unapproved products.

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

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

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

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Marketed Products

Xywav is manufactured at our Athlone facility.

Xywav, like Xyrem, is a Schedule III controlled substance in the U.S.

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 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 under the Patheon Agreement entered into with Patheon in 2015.

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

commercial supply and rely on Patheon to supply Xyrem for other markets, though we are not required to purchase Xyrem exclusively from Patheon.

Xywav and Xyrem .

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

Most of our U.S.

commercial supply is manufactured by Patheon.

The current term of the Patheon Agreement will expire in December 2026, subject to further automatic two-yearly extensions if Patheon is then providing manufacturing services for any product, unless either party provides prior notice of termination.

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

Xywav, like Xyrem, is a Schedule III controlled substance in the U.S.

The API of Xywav are the calcium, magnesium, potassium and sodium salts of GHB, which are Schedule I controlled substances in the U.S.

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 GHB 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.

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

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under highly controlled and standardized conditions.

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

The term of the agreement with WuXi (Hong Kong) 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.

In January 2026, we enter ed into a development and services agreement with Lonza AG and Lonza Sales AG for the commercial supply of Ziihera in the U.S.

beginning in 2029.

Modeyso is manufactured by Adare, which is a sole source supplier.

We source the API of Modeyso from ChemSpec USA, LLC.

Adare is the sole provider of our commercial and clinical supply of Modeyso;

however, we are not required to purchase Modeyso exclusively from Adare.

If Adare does not or is not able to supply us with Modeyso for any reason, it may take time and resources to implement and execute the necessary technology transfer to another processor, this could be executed with a relative low technical risk and minimal risk of delay, as such this is unlikely to negatively impact our anticipated revenues from Modeyso.

Zepzelca is manufactured by Simtra.

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Rylaze is currently manufactured by Patheon, and the API of Rylaze is manufactured by AGC Biologics A/S.

The initial term of the agreement with Patheon 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.

The initial term of the agreement with Patheon expired in December 2025 and allows for automatic two-year extensions, unless either party provides advance notice of its intent to terminate the agreement.

Patheon informed us that they will terminate the manufacturing agreement effective end of 2026.

The initial term of the agreement with AGC Biologics A/S will expire in October 2026 and will then be subject to automatic three-year extensions, unless either party provides advance notice of its intent to terminate the agreement.

Vyxeos is manufactured by Simtra, which is a sole source supplier from a single site location, using our CombiPlex technology platform.

Vyxeos is manufactured by Simtra, which is a sole source supplier from a single site location, using our CombiPlex platform.

CombiPlex products represent formulations with increased manufacturing complexities associated with producing drug delivery vehicles encapsulating two or more drugs that are maintained at a fixed ratio and, in the case of Vyxeos, two drugs that are co-encapsulated in a freeze-dried liposomal format.

Our manufacturing agreement with Simtra expires in August 2025, subject to automatic three-year renewal terms, unless either party provides advance notice of its intent to terminate the agreement.

Our manufacturing agreement with Simtra expires in December 2029, subject to automatic three-year renewal terms, unless either party provides advance notice of its intent to terminate the agreement.

While other contract manufacturers may be able to produce Vyxeos, the proprietary technology that supports the manufacture of Vyxeos is not easily transferable.

The marketing authorization in the EU for Vyxeos also requires us to comply with certain manufacturing-related post-approval commitments.

We are our own sole supplier of, and we believe that we are currently the sole worldwide producer of, defibrotide API.

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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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The patent laws of ex-U.S.

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

countries differ from those in the 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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These patents expire from 2033 to 2041.

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

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 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.

For example, we received notices in June 2021 and February 2023, that Lupin and Teva, respectively, filed ANDAs for generic versions of Xywav.

For example, we received notices in June 2021, February 2023 and July 2025 that Lupin, Teva and Granules, respectively, filed ANDAs for generic versions of Xywav.

In January 2026, we received notices from Tris Pharma that it had filed with FDA a Section 505(b)(2) NDA for generic versions of Xyrem and Xywav.

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.

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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 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, additional companies may challenge our U.S.

As a result, our Orange Book-listed patents have periods of exclusivity between March and September 2033.

Although we have settled all patent litigation against the ten companies that filed ANDAs seeking to market a generic version of Xyrem, additional companies may challenge our U.S.

patents for Xyrem in the future.

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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.

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.

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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.

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

In November and December 2022, ten companies sent us notices that they had filed ANDAs seeking approval to market a generic version of Epidiolex.

Epidiolex has received ODE to treat seizures associated with LGS and DS, which expired in September 2025, and TSC, which expires in July 2027.

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 Ziihera, which expires in 2034 (excluding any adjustments or extensions).

As a result of the Chimerix Acquisition, we acquired a portfolio of U.S.

and international patents and patent applications for Modeyso, which cover methods of use and pharmaceutical formulations.

There are seven patents listed in the Orange Book, with the last patent set to expire on January 30, 2037.

This expiration excludes an additional two years of patent term extension, for which the application is currently pending with the USPTO.

Modeyso has also received orphan drug designation and new chemical entity status, which will expire on August 6, 2030.

ODE for Modeyso is expected and, if granted, will expire on August 6, 2032.

In December 2019, we entered into an exclusive license agreement with PharmaMar pursuant to which we obtained exclusive U.S.

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A request for extension (CSP) has also been filed in Canada.

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 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 October 2025, we received approval for Zepzelca in a second indication, as a first-line maintenance treatment for adults with ES-SCLC in combination use of lurbinectedin with atezolizumab.

ODE for the second indication is anticipated, which if granted, would expire in October 2032.

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.

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.

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We have a portfolio of U.S.

patents and patent applications for Vyxeos and the CombiPlex technology platform relating to various compositions and methods of making and use.

These include seven U.S.

patents covering Vyxeos compositions and methods of use expiring between 2025 and 2032 and two U.S.

patents covering CombiPlex (which also cover Vyxeos) expiring in January 2027.

These patents are listed in the Orange Book.

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

patents and patent applications for Vyxeos and the CombiPlex platform relating to various compositions and methods of making and use.

These include six Orange Book listed U.S.

patents covering Vyxeos compositions and methods of use expiring between 2026 and 2033 (including pediatric extensions) and two U.S.

patents covering CombiPlex (which also cover Vyxeos) expiring in July 2027 (including pediatric extensions).

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.

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patents are listed in the Orange Book.

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.

In December 2024, FDA accepted an ANDA from Almaject for a generic version of Defitelio.

We received notice by Almaject of this ANDA filing in March 2025.

In April 2025, we filed a patent infringement lawsuit against Almaject.

As a result of this lawsuit, we expect that a stay of approval of up to 30 months will be imposed by FDA on Almaject’s ANDA.

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.

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.

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 Ziihera, which expires in 2034 (excluding any adjustments or extensions).

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

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composition of matter patent relating to JZP898, which, if granted, expires in 2040 (excluding any adjustments or extensions).

• Suvecaltamide (JZP385) .

Through the acquisition of Cavion in 2019, we obtained a portfolio of U.S.

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

The portfolio includes a U.S.

composition of matter patent relating to suvecaltamide, which expires in 2027, but which may be extended to 2032 depending on regulatory approval.

patent to the treatment of ET may provide supplemental protection to 2039.

Through a license agreement with Sumitomo 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 JZP441.

The portfolio contains a U.S.

composition of matter patent relating to JZP441, which expires in 2040 (excluding any adjustments or extensions).

In addition, we have rights to a number of trademarks and service marks, and pending trademark and service mark applications, in the U.S.

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As a global pharmaceutical company, our activities are subject to extensive regulation in the U.S., Europe and other countries where we do business.

Regulatory requirements encompass the entire life cycle of pharmaceutical products, from research and development activities to marketing approval, manufacturing, labeling, packaging, adverse event and safety reporting, storage, advertising, promotion, sale, pricing and reimbursement, recordkeeping, distribution, importing and exporting.

Regulatory requirements encompass the entire life cycle of pharmaceutical products, from R&D activities to marketing approval, manufacturing, labeling, packaging, adverse event and safety reporting, storage, advertising, promotion, sale, pricing and reimbursement, recordkeeping, distribution, importing and exporting.

Regulations differ from country to country and are constantly evolving.

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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 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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Generally, products may be eligible for one or more of these programs if they are intended for serious or life-threatening diseases or conditions, have potential to address unmet medical needs, or may provide meaningful benefit over existing treatments.

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 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.

In December 2020, we initiated the submission of a BLA for Rylaze for ALL under the RTOR pilot program, which was approved by FDA in June 2021.

Modeyso was also granted fast track designations and priority review for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation, which was granted accelerated approval in August 2025.

During its review of an application, FDA evaluates whether the product demonstrates the required level of safety and efficacy for the indication for which approval is sought and conducts the inspections and audits described above.

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Even if a product is approved, the approval may be subject to limitations based on FDA’s interpretation of the data submitted in the application.

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.

Further, FDA granted Accelerated Approval to Zepzelca for relapsed SCLC based on data from a Phase 2 trial, which approval is contingent upon verification and description of clinical benefit in a post-marketing clinical trial.

document a clinical benefit in the case of products approved under accelerated approval regulations.

FDA granted accelerated approval to Zepzelca for relapsed SCLC based on data from a Phase 2 trial and to Modeyso for diffuse midline glioma harboring an H3 K27M mutation with progressive diseases following prior therapy;

both approvals are contingent upon verification and description of clinical benefit in a post-marketing clinical trial.

In addition, if FDA determines that a REMS is necessary to ensure that the benefits of the product outweigh the risks, a sponsor may be required to include a proposed REMS (either as part of the application or after approval), which may include a patient package insert or a medication guide to provide information to consumers about the product’s risks and benefits;

a plan for communication to healthcare providers;

or conditions on the product’s prescribing or distribution referred to as elements to assure safe use.

or conditions on the product’s prescribing or distribution referred to as ETASU.

Xywav and Xyrem are required to have a REMS.

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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 EMA.

There is a “centralized” procedure allowing submission of a single MAA 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).

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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.

reached an agreement in principle on the framework for their future relationship, the TCA.

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

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Northern Ireland, however, continues to be covered by the marketing authorizations granted by the EC.

The maximum timeframe for the evaluation of an application in the EU under the centralized procedure is 210 days, subject to certain exceptions and clock stops.

An initial marketing authorization granted in the EU is valid for five years, with renewal subject to re-evaluation of the risk-benefit profile of the product.

The maximum timeframe for the evaluation of a MAA in the EU under the centralized procedure is 210 days, subject to certain exceptions and clock stops.

An initial marketing authorization granted in the EU is valid for five years, with renewal subject to re-evaluation of the risk-benefit profile of the medicinal product.

Once renewed, the authorization is usually valid for an unlimited period unless the national competent authority or the EC decides on justified grounds to proceed with one additional five-year renewal.

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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.

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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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 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.

The SmPC is the document describing the properties and the officially approved conditions of use of a medicine and providing information to physicians concerning the safe and effective use of the medicinal product.

Promotional activity that does not comply with the SmPC is considered off-label and is prohibited in the EU.

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For example, in November 2020, the OIG issued a Special Fraud Alert to highlight certain inherent risks of remuneration related to speaker programs sponsored by drug and device companies, which may not in all circumstances qualify under either safe harbor or statutory exception protection.

The Special Fraud Alert sent a clear signal that speaker programs will be subject to potentially heightened enforcement scrutiny, in particular for those programs with certain characteristics identified as risk factors by OIG, including meals exceeding modest value or where alcohol is made available;

The Special Fraud Alert sent a clear signal that speaker programs will be subject to potentially heightened enforcement scrutiny, in particular for those programs with certain characteristics identified as risk factors by the OIG, including meals exceeding modest value or where alcohol is made available;

lack of substantive or new content presented;

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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 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.

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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, 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 CHMP 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.

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Controlled Substance Regulations

A drug product approved by FDA may be subject to scheduling as a controlled substance under the CSA depending on the drug’s potential for abuse.

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

The DEA is the U.S.

federal agency responsible for domestic enforcement of the federal CSA and similar state and foreign laws based on the drug’s potential for abuse, among other factors.

Controlled substances 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 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.

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Certain product candidates we are developing contain controlled substances as defined in the CSA.

Drug products approved by FDA that contain cannabis or cannabis extracts may be controlled substances and will be rescheduled to Schedules II-V after approval or, like Epidiolex, removed completely from the schedules by operation of other laws.

Drug products approved by FDA that contain cannabis or cannabis extracts may be controlled substances and, if so, will be rescheduled to Schedules II-V after approval or, like Epidiolex, removed completely from the schedules by operation of other laws.

The DEA limits the quantity of certain Schedule I and II controlled substances that may be manufactured and procured in the U.S.

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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.

In addition, the third parties who perform our clinical and commercial manufacturing, distribution, dispensing and clinical studies for Xywav and Xyrem are required to maintain necessary DEA registrations and state licenses.

In addition, the third parties who perform certain activities related to our products that contain controlled substances, including manufacturing, distributing, dispensing and conducting clinical studies for Xywav and Xyrem, are required to maintain necessary DEA registrations and state licenses and comply with federal and state controlled substance requirements.

The DEA periodically inspects facilities for compliance with its rules and regulations.

For all controlled substances, there are potential criminal and civil penalties that apply for the failure to meet applicable legal requirements, and, in general, healthcare

professionals may be required to have a federal and/or state license in order to handle, prescribe, or dispense controlled substances.

Other Regulations

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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.

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

In 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, 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.

Compliance with these laws requires a flexible privacy framework and substantial resources, and compliance efforts will likely be an increasing and substantial cost in the future.

We may be subject to fines, penalties, or private actions in the event of non-compliance with such laws.

In particular, we are subject to the GDPR, 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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The Hatch-Waxman Act also permits a patent term extension of up to five years (but not beyond 14 years from the date of approval) for an NDA, including a Section 505(b)(2) NDA, that is approved for a product that contains an active ingredient that has not previously been approved.

The extension, which compensates for patent term lost during product development and FDA regulatory review process, is generally equal to the sum of one-half the time between the effective date of an IND application and the submission date of an NDA, and all of the time between the submission date of an NDA and the approval of that application.

The extension, which compensates for patent term lost during product development and

FDA regulatory review process, is generally equal to the sum of one-half the time between the effective date of an IND application and the submission date of an NDA, and all of the time between the submission date of an NDA and the approval of that application.

It is available for only one patent for a given product, and it must be a patent that claims the product or a method of using or manufacturing the product.

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In the EU, innovative medicinal products that are subject to marketing authorization on the basis of a full dossier qualify for eight years’ data exclusivity upon marketing authorization and an additional two years’ market exclusivity.

Data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic application or biosimilar application for eight years from the date of authorization of the innovative product, after which a generic or biosimilar marketing authorization application can be submitted, and the innovator’s data may be referenced.

Data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic application or biosimilar application for eight years from the date of authorization of the innovative product, after which a generic or biosimilar MAA can be submitted, and the innovator’s data may be referenced.

However, the generic product or biosimilar products cannot be marketed in the EU for a further two years thereafter.

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.

In December 2025, the European Parliament and the Council of the EU reached a provisional agreement on the comprehensive reform of the EU pharmaceutical legislation to enhance the availability, accessibility, and affordability of medicinal products across the EU.

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

Among others, the new legislation provides for certain changes to regulatory exclusivity periods.

The provisional agreement is still subject to the formal approval by the European Parliament and the Council of the EU and subsequent publication in the Official Journal of the EU.

Orphan Drug and Other Exclusivities

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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.

Vyxeos was granted ODE by FDA for the treatment of adults with AML until August 2024 and pediatric patients ages 1 year and older with AML until March 2028.

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

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

Ziihera has been granted ODE through November 2031 for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC3+) BTC, as detected by an FDA-approved test.

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.

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We consider seeking pediatric exclusivity for our products whenever appropriate.

For example, in response to a written request from FDA, we conducted a Phase 3 clinical trial to assess the safety and efficacy of Xyrem in children and adolescents aged seven to 17 who have narcolepsy with cataplexy, and submitted study results in a supplement to the Xyrem NDA, seeking approval for this indication.

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 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.

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 marketing authorization.

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 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.

Defibrotide was granted OME 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.

Ziihera has been granted OME through June 2033, for the treatment of BTC.

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 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.

Under the Medicaid Drug Rebate Program, as a condition of having federal funds made available 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.

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.

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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.

The 340B ceiling price is calculated using a statutory formula, which is based on the average manufacturer price and rebate amount for the covered outpatient drug as calculated under the Medicaid Drug Rebate Program, and in general, products subject to Medicaid price reporting and rebate liability are also subject to the 340B ceiling price calculation and discount requirement.

discount requirement.

A regulation regarding the calculation of the 340B ceiling price and the imposition of civil monetary penalties on manufacturers that knowingly and intentionally overcharge covered entities became effective on January 1, 2019.

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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.

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

Further, the Inflation Reduction Act of 2022 among other things, requires the U.S.

Department of Health and Human Services Secretary to negotiate, with respect to Medicare units and subject to a specified cap, the price of a set number of certain high Medicare spend drugs and biologicals per year starting in 2026, penalizes manufacturers of certain Medicare Parts B and D drugs for price increases above inflation, and makes several changes to the Medicare Part D benefit, including a limit on annual out-of-pocket costs and a change in manufacturer liability under the program, which could negatively affect our business and financial condition.

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

Further, the IRA, among other things, requires the HHS Secretary to negotiate, with respect to Medicare units and subject to a specified cap, the price of a set number of certain high Medicare spend drugs and biologicals per year starting in 2026 and penalizes manufacturers of certain Medicare Parts B and D drugs for price increases above inflation.

The IRA also made several changes to the Medicare Part D benefit, including a limit on annual out-of-pocket costs and a change in manufacturer liability under the program, which could negatively affect our business and financial condition.

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.

Further, HHS imposes rebates on many Medicare Part B and Medicare Part D products to penalize price increases that outpace inflation on an annual basis.

HHS has also been empowered to negotiate the price of certain single-source drugs that have been on the market for at least 7 years covered under Medicare as part of the Medicare Drug Price Negotiation Program.

Each year up to twenty (20) products will be selected by HHS for the Medicare Drug Price Negotiation Program.

Drugs and biologics designated for one or more rare diseases or conditions, and approved only for such rare indications, are excluded from the Medicare Drug Price Negotiation Program.

Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.

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 VA FSS pricing program.

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

State legislatures are also becoming increasingly aggressive in passing legislation that could expand the availability of the ceiling price under the federal government's 340B program.

Legislative and regulatory proposals to reform the regulation of the U.S.

pharmaceutical industry and reimbursement for pharmaceutical drugs are continually changing.

On July 4, 2025, President Trump signed into law the OBBBA, which includes significant changes to Medicaid, Medicare, and the ACA.

These reforms are anticipated to decrease federal health care spending by approximately $1 trillion by significantly reducing Medicaid spending and enrollment, making changes to the Medicare program, and altering ACA marketplace enrollment provisions.

The OBBBA is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program.

The OBBBA also narrows access to ACA marketplace exchange enrollment and declines to extend the ACA enhanced advanced premium tax credits that expired at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance.

Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expired ACA subsidies.

Other legislative and regulatory proposals that have recently been considered include, among other things,

proposals to limit the terms of patent litigation settlements with generic sponsors, to define certain conduct around patenting and new product development as unfair competition, to address the scope of orphan drug exclusivity and to facilitate the importation of drugs into the U.S.

from other countries, and changes to health care coverage.

For example, the current administration has announced agreements with several pharmaceutical companies that require the drug manufacturers to offer Medicaid programs prescription drug MFN pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues.

The current administration is pursuing policies to reduce regulations and expenditures across government agencies including at HHS, the FDA, CMS and related agencies.

These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business.

Other recent actions, for example, include (1) directing agencies to reduce agency workforce and cut programs;

(2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives, including by improving upon the Medicare Drug Price Negotiation Program and establishing MFN pricing for pharmaceutical products;

(3) imposing tariffs on imported pharmaceutical products;

and (4) as part of the MAHA Commission’s Strategy Report released in September 2025, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising.

Additionally, the current administration recently called on U.S.

Congress to enact “The Great Healthcare Plan,” to codify and expand MFN pricing, lower government subsidies to private insurance companies, increase healthcare price transparency, expand pharmaceutical drugs available for over-the-counter purchase, and enact restrictions on PBM payment methodologies, among other things.

These actions and policies may significantly reduce U.S.

drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks.

In June 2024, the U.S.

Supreme Court’s Loper Bright decision greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations.

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

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The outcome of HTA regarding specific medicinal products will often influence the pricing and reimbursement status granted to these medicinal products by the competent authorities of individual EU member states.

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 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.

In December 2021, the European Parliament and the Council of the EU adopted HTA Regulation 2021/2282, which intends to boost cooperation and collaboration among EU member states in assessing health technologies, including new medicinal products.

The HTA Regulation entered into application in January 2025 establishes a framework of rules, procedures and methodologies for conducting Joint Clinical Assessments at EU level which are intended to support EU member states in their national HTA processes.

Under this regulation, 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.

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For more information, including with respect to recent legal developments regarding the Medicaid Drug Rebate Program, Medicare Part B, and the 340B program, see the risk factors under the headings “ Adequate coverage and reimbursement from third party payors may not be available for our products and we may be unable to successfully contract for coverage from pharmacy benefit managers and group purchasing organizations, which could diminish our sales or affect our ability to sell our products profitably;

conversely, to secure coverage from these organizations, we may be required to pay rebates or other discounts or other restrictions to reimbursement that could diminish our sales,” “ The pricing of pharmaceutical products has come under increasing scrutiny as part of a global trend toward healthcare cost containment and resulting changes in healthcare law and policy may impact our business in ways that we cannot currently predict, which could have a material adverse effect on our business and financial condition” and “If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate Program or other governmental pricing programs, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects” in Part I, Item 1A of this Annual Report on Form 10‑K.

conversely, to secure coverage from these organizations, we may be required to pay rebates or other

discounts or other restrictions to reimbursement that could diminish our sales,” “ The pricing of pharmaceutical products has come under increasing scrutiny as part of a global trend toward healthcare cost containment and resulting changes in healthcare law and policy may impact our business in ways that we cannot currently predict, which could have a material adverse effect on our business and financial condition” and “If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate Program or other governmental pricing programs, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects” in Part I, Item 1A of this Annual Report on Form 10‑K.

Patient Copay Assistance and Free Product Programs

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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.

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.

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.

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

About Jazz Pharmaceuticals plc

6 unchanged sentences

Our website is www.jazzpharmaceuticals.com.

We file or furnish pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended, as applicable, our Annual Reports on Form 10‑K, Quarterly Reports on Form 10‑Q, Current Reports on Form 8-K, amendments to those reports, proxy statements and other information electronically with the SEC.

We file or furnish pursuant to Section 13(a) or 15(d) of the Exchange Act, as applicable, our Annual Reports on Form 10‑K, Quarterly Reports on Form 10‑Q, Current Reports on Form 8-K, amendments to those reports, proxy statements and other information electronically with the SEC.

Through a link on our website, we make copies of our periodic and current reports, amendments to those reports, proxy statements and other information available, free of charge, as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

Information found on, or accessible through, our website is not a part of, and is not incorporated into, this Annual Report on Form 10‑K.

Such reports and other information may also be accessed through the SEC’s website at www.sec.gov.

Information found on, or accessible through, our website is not a part of, and is not incorporated into, this Annual Report on Form 10‑K or any other report that we file with or furnish to the SEC.

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