What changed in this filing

/stocks — the workspaceLOADING

Item 7. Management’s Discussion and Analysis

2026-02-24 compared with 2025-02-26 · 318 added, 328 removed, 434 unchanged (60% of the section changed)

2 unchanged sentences

This discussion contains forward-looking statements that involve risks and uncertainties.

When reviewing the discussion below, you should keep in mind the substantial risks and uncertainties that impact or could impact our business.

In particular, we encourage you to review the risks and uncertainties described in “Risk Factors” in Part I, Item 1A in this Annual Report on Form 10‑K.

These risks and uncertainties could cause actual results to differ materially from those projected in forward-looking statements contained in this report or implied by past results and trends.

Forward-looking statements are statements that attempt to forecast or anticipate future developments in our business, financial condition or results of operations.

See the “Cautionary Note Regarding Forward-Looking Statements” that appears at the beginning of this Annual Report.

These statements, like all statements in this report, speak only as of the date of this Annual Report on Form 10-K (unless another date is indicated), and we undertake no obligation to update or revise these statements in light of future developments.

You should review the risks and uncertainties described in “Risk Factors” in Part I, Item 1A in this Annual Report on Form 10‑K for a discussion of important factors that could cause actual results to differ materially from those projected in forward-looking statements contained in this report or implied by past results and trends.

Forward-looking statements are statements that attempt to forecast or anticipate future developments in our business, financial condition or results of operations.

See the “Cautionary Note Regarding Forward-Looking Statements” that appears at the beginning of this Annual Report.

See the “Cautionary Note Regarding Forward-Looking Statements” that appears at the beginning of this Annual Report on Form 10-K.

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.

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 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.

We focus on rare disease, 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 across our product portfolio, which focuses on neuroscience and oncology medicines;

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

• Continuing to build a flexible, efficient and productive development engine for targeted therapeutic areas 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.

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 Part I, Item 1 of this Annual Report on Form 10-K.

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 Part I, Item 1 of this Annual Report on Form 10-K.

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

7 unchanged sentences

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)

Product Indications Initial Approval Date Markets

9 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

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

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

Rare Sleep Disorders

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.

Since there is no cure for narcolepsy and long-term disease management is needed, we believe that Xywav represents an important therapeutic option for patients with this sleep disorder.

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

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.

ODE extends through January 2028.

Our commercial efforts are focused on educating patients and physicians on the strength of clinical evidence that supports the use of Xywav for treating narcolepsy and IH.

Xywav has demonstrated efficacy for the treatment of cataplexy and EDS in narcolepsy and multiple daytime symptoms such as sleep inertia in IH.

Analysis from the Phase 4 DUET trial showed improvements across multiple polysomnography measures in both narcolepsy and IH, suggesting Xywav improves measures of sleep fragmentation in these conditions.

In addition, we are also focused on educating patients and physicians on the long-term health impacts of high sodium intake, and how the use of Xywav helps address a modifiable risk factor for cardiovascular morbidity.

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 2027 (which was subsequently extended to January 2028).

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

market by Avadel.

market by Avadel in June 2023.

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

1 unchanged sentence

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 was approved by FDA in 2002, and contains 1640mg of sodium per 9gram dose per night.

Xyrem is indicated for the treatment of cataplexy or 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.

2 unchanged sentences

commercial launch of Xywav for the treatment of IH in adults in November 2021.

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

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

prolonged and non-restorative nighttime sleep.

An estimated 37,000 people in the U.S.

3 unchanged sentences

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.

Exiting 2024, there were approximately 14,150 patients taking Xywav, including approximately 10,250 patients with narcolepsy and approximately 3,900 patients with IH.

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

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.

Rare Epilepsies

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

Epidiolex was approved in the U.S.

in June 2018 for the treatment of seizures associated with two rare and severe forms of epilepsy, LGS and DS, in patients two years of age and older, and subsequently approved in July 2020 for the treatment of seizures associated with TSC in patients one year of age and older.

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

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

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

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

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

Epidyolex is now launched in all five key European markets:

United Kingdom, Germany, Italy, Spain and France.

Epidyolex was also approved for adjunctive therapy of 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 or under review for this indication in other markets.

Outside the U.S.

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

Rylaze was approved by FDA in June 2021 under the Real-Time Oncology Review 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 or LBL in pediatric and adult patients one month and older who have developed hypersensitivity to E.

Epidyolex was also approved for adjunctive therapy of 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.

Rare Oncology

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

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

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.

We completed the Chimerix Acquisition in April 2025 for a total cash consideration of $944.2 million, adding Modeyso, a protease activator of the 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.

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 metastatic SCLC with disease progression on or after platinum-based chemotherapy.

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

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

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.

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.

4 unchanged sentences

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 under the trade name Enrylaze.

This product has also been approved in Great Britain, Canada and Switzerland.

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.

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.

In collaboration with Roche, we have an ongoing Phase 3 pivotal clinical trial of 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 an sNDA in the first half of 2025 to support this combination in the first-line maintenance setting.

We acquired exclusive development and commercialization rights to Ziihera in 2022 through an exclusive 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

was approved by FDA in November 2024 and 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.

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

Utilization of Defitelio is in part driven by evolving treatment practices in HSCT, and we are continuing to educate healthcare professionals on the clinical profile of Defitelio and its role in treating VOD and/or severe VOD following HSCT.

Vyxeos is a treatment for adults with newly-diagnosed t-AML, or AML-MRC.

In March 2021, FDA approved a revised label to include a new indication to treat newly-diagnosed t-AML, or AML-MRC, in pediatric patients aged one year and older.

We continue to expand into new markets internationally as the product receives approvals and reimbursement in relevant markets.

In the U.S., with ongoing trends towards lower-intensity treatments and away from intensive chemotherapy regimens for AML, we have seen increasing competition from other therapeutic options.

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.

Other Rare Disease

In October 2025, we divested Sativex to CNX Therapeutics, who will assume responsibility for Sativex in all countries it is approved.

Our existing partnerships will transition to CNX Therapeutics and it will take responsibility for commercialization in those markets previously owned by us.

We will continue to manufacture Sativex during the transition period given the complexity of the product and all external growing partnerships will transition to CNX Therapeutics.

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.

Within our oncology R&D program, in October 2022, we announced an exclusive licensing and collaboration agreement with Zymeworks providing us the right to acquire development and commercialization rights to Zymeworks' zanidatamab across all indications in the U.S., Europe, Japan and all other territories except for those Asia/Pacific territories previously licensed by Zymeworks.

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.

Within our oncology R&D program, in October 2022, we announced an exclusive licensing and collaboration agreement with Zymeworks providing us development and commercialization rights to Zymeworks' zanidatamab across all indications in the U.S., Europe, Japan and all other territories except for those Asia/Pacific territories previously licensed by Zymeworks.

In December 2022, we exercised the option to continue with the exclusive development and commercialization rights to zanidatamab.

3 unchanged sentences

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

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

Following positive data from a pivotal Phase 2 clinical trial evaluating zanidatamab monotherapy in patients with previously treated advanced or metastatic HER2-amplified 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 approval for this BLA in November 2024.

EMA has validated our MAA for zanidatamab in second-line BTC;

we anticipate a response to our MAA in 2025.

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

In July 2024, we announced the initiation of the Phase 3 EmpowHER-BC-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.

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

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:

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-BC-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.

We are collaborating with Roche on a pivotal Phase 3 clinical trial evaluating Zepzelca in combination with Tecentriq for use as maintenance therapy in first-line extensive-stage SCLC.

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

In December 2021, our licensor PharmaMar initiated a confirmatory trial in second-line SCLC.

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

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

In addition, 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.

Preliminary findings from this study presented at the 2024 World Conference on Lung Cancer demonstrated Zepzelca provided clinical

benefit when administered as second-line SCLC therapy.

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

In June 2022, we announced FDA had cleared our Investigational New Drug application for JZP815 and, in October 2022, we enrolled the first patient in a Phase 1 trial.

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

In April 2022, we announced that we had entered into a licensing and collaboration agreement with Werewolf to acquire exclusive global development and commercialization rights to Werewolf's investigational WTX-613, now referred to as JZP898.

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.

In April 2025, we completed the Chimerix Acquisition for $944.2 million in cash, and Chimerix is now our wholly owned subsidiary.

The lead clinical asset acquired from Chimerix is Modeyso, a novel first-in-class small molecule that is a protease activator of the ClpP that also inhibits DRD2.

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.

The ongoing Phase 3 ACTION trial is evaluating Modeyso in newly diagnosed, non-recurrent H3 K27M-mutant diffuse glioma patients following radiation treatment, potentially extending this treatment option into the front-line setting.

In June 2022, we announced FDA had cleared our IND for JZP815 and, in October 2022, we enrolled the first patient in a Phase 1 trial.

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

In April 2022, we announced that we had entered into a licensing and collaboration agreement with Werewolf to acquire exclusive, worldwide development and commercialization rights to Werewolf's investigational WTX-613, now referred to as JZP898.

Under the terms of the agreement, we made an upfront payment of $15.0 million to Werewolf, and Werewolf is eligible to receive development, regulatory and commercial milestone payments of up to $1.26 billion.

If approved, Werewolf is eligible to receive a tiered, mid-single-digit percentage royalty on net sales of JZP898.

This transaction underscores our commitment to enhancing our pipeline to deliver novel oncology therapies to patients, and also provides us with an opportunity to expand into immuno-oncology.

This provides us with an opportunity to expand into immuno-oncology.

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

We initiated a Phase 1 clinical trial of JZP898 in late 2023.

Our neuroscience R&D efforts include 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.

In December 2021, we initiated a Phase 2 clinical trial for suvecaltamide (JZP385), for ET.

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

In June 2024, we announced the ET trial did not achieve statistical significance on the primary and key secondary endpoint for the 30 mg dose.

In January 2025, we announced that consistent with the results from the ET trial, results from the Parkinson's disease tremor trial did not show statistical significance on the primary and key secondary endpoint.

Based on these results, we will not continue the ET or PDT development program.

We are exploring options for the suvecaltamide program.

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 narcolepsy patients.

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 JZP441, also known as DSP-0187, a potent, highly selective oral orexin-2 receptor agonist with potential application for the treatment of narcolepsy, IH and other sleep disorders.

Under the terms of the agreement, we made an upfront payment of $50.0 million to Sumitomo, and Sumitomo is eligible to receive development, regulatory and commercial milestone payments of up to $1.09 billion.

If approved, Sumitomo is eligible to receive a tiered, low double-digit royalty on our net sales of JZP441.

In November 2023, we announced that we achieved initial proof-of-concept in our Phase 1 clinical trial program in healthy volunteers as demonstrated by the Maintenance of Wakefulness Test (MWT).

At that time, we also noted 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 future development efforts.

In November 2023, we enrolled our first patient in a Phase 1 trial of JZP898.

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 November 2023, we announced that we achieved initial proof-of-concept in our Phase 1 clinical trial program in healthy volunteers as demonstrated by the MWT.

In 2025, we initiated a small Phase 1b trial of JZP441 in narcolepsy Type 1 patients.

Based on our continued assessment of the molecule, we made the decision to stop the development of JZP441 and end our partnership with Sumitomo.

In August 2025, we announced that we entered a global license agreement with Saniona to obtain exclusive worldwide rights to develop SAN2355, now referred to as JZP053, for epilepsy and other potential indications.

JZP053 is a preclinical, selective small molecule activator of Kv7.2/Kv7.3 potassium channels, a mechanism validated for seizure suppression.

Under the terms of the agreement, we made an upfront payment to Saniona of $42.5 million.

Saniona is eligible to receive up to $192.5 million in development and regulatory milestones, up to $800 million in commercial milestone payments and tiered royalties ranging from mid-single digits to low-double digits on net sales of commercial products resulting from the development of JZP053.

This transaction further expands our early-stage neuroscience pipeline building on our existing expertise in the treatment of epilepsy.

In November 2025, we initiated a Phase 1b trial evaluating Epidiolex as an adjunctive treatment in reducing the frequency of focal seizures compared to the baseline as well as the effect of Epidiolex on health outcome endpoints in early line and refractory participants with focal-onset seizures.

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

Product Candidates Description

Zanidatamab 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 extensive-stage SCLC in combination with Tecentriq (collaboration with Roche) (ongoing trial)

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

Vyxeos AML or high-risk 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

1 Also known as ONC206

2 Also known as ONC212

3 Also known as SAN2355

2025 Highlights and Recent Developments

Regulatory Submissions, Approvals and Commercial Launches

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

This BLA received Priority Review, and zanidatamab was approved by FDA under the trade name Ziihera in November 2024.

• Launched Ziihera in the U.S.

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

• Based on results from the Phase 2b second-line BTC trial, Ziihera was incorporated into NCCN and ESMO guidelines for BTC treatment.

• Submitted MAA to EMA for zanidatamab in second-line BTC;

EMA validated the MAA.

• Reimbursement for Epidyolex was secured in Switzerland, Czech Republic, Estonia, Iceland, Poland and Slovakia for DS, LGS and TSC and in Taiwan for DS and TSC.

• In April 2025, Ziihera received a positive CHMP opinion for the treatment of advanced HER2-positive BTC.

• The sNDA submission for the combination of Zepzelca with atezolizumab or atezolizumab and hyaluronidase-tqjs was granted priority review by FDA in June 2025 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.

• Following the Chimerix Acquisition in April 2025, Modeyso received FDA approval in August 2025 and was subsequently launched 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 and Zepzelca were included in the NCCN® Clinical Practice Guidelines in Oncology in 2025.

Research & Development

• Initiated zanidatamab Phase 3 EmpowHER-BC-303 trial in previously treated HER2-positive breast cancer patients whose disease has progressed on previous T-DXd treatment.

• Initiated zanidatamab Phase 2 DiscovHER-Pan-206 trial to evaluate HER2-positive solid tumors.

• Announced positive top-line findings from the Phase 3 IMforte trial, showing statistically significant and clinically meaningful benefits for Zepzelca and atezolizumab in combination in first-line maintenance therapy for extensive- stage SCLC.

• Reported findings from two Phase 2 trials of suvecaltamide in ET and PDT;

these trials did not achieve statistical significance compared to placebo on the primary or key secondary endpoints.

• Reported top-line results from an ongoing Phase 3 trial of Epidyolex for LGS, DS and TSC in Japan.

While the trial did not meet the primary efficacy endpoint, numeric improvements were observed in the primary and several secondary endpoints.

• Announced positive top-line results from the Phase 3 HERIZON-GEA-01 trial, showing statistically significant and clinically meaningful progression-free survival and overall survival benefits for zanidatamab and chemotherapy with or without tislelizumab in HER2-positive locally advanced or metastatic GEA.

• Initiated zanidatamab Phase 2 EmpowHER-BC-208 trial to evaluate HER2-positive neoadjuvant and adjuvant breast cancer.

• Initiated a Phase 1b trial of Epidiolex in focal-onset seizures.

Challenges, Risks and Trends Related to Our Business

Our operating plan assumes that Xywav, with 92% lower sodium compared to high-sodium oxybates (depending on the dose) absence of a sodium warning and dosing titration option, will remain the #1 branded oxybate treatment for narcolepsy;

In 2025, Xywav revenues meaningfully contributed to our business.

Our current 2026 operating plan assumes that Xywav, with 92% lower sodium compared to high-sodium oxybates (depending on the dose), a dosing titration option and an absence of a sodium warning, will remain the #1 branded oxybate treatment for narcolepsy;

the position it held based on revenue in the fourth quarter of 2025 .

3 unchanged sentences

In an effort to support strong adoption of Xywav and patient success, we are focused on facilitating payor coverage for Xywav and providing robust patient copay and savings programs.

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

Avadel’s Lumryz was launched in the U.S.

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, which was launched in the U.S.

market in June 2023.

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

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

On September 15, 2023, we filed a motion for summary judgment.

On October 20, 2023, Avadel and FDA filed cross motions for summary judgment.

Oral argument on these motions was held on May 10, 2024, and on October 30, 2024, the District Court issued an order denying our motion for summary judgment and granting Avadel’s and FDA’s cross-motions for summary judgment.

We have appealed the matter to the United States Court of Appeals for the District of Columbia Circuit.

We cannot at this time predict the timing or ultimate outcome of this litigation or the impact of this litigation on our business.

In addition, in January 2023, our oxybate products began to face competition from an AG version of high-sodium oxybate pursuant to a settlement agreement we entered into with an ANDA filer.

In July 2023, a volume-limited ANDA filer launched an AG version of high-sodium oxybate.

These AG products have negatively impacted and are expected to continue to negatively impact Xyrem and Xywav sales for patients with narcolepsy.

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

Specifically, a wholly-owned subsidiary of Hikma launched its AG version of sodium oxybate in January 2023 and Amneal launched its AG version of 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 a substantial increase in the royalty rate beginning in January 2024, which will remain fixed for the duration of the agreement's term.

We are also paid for supply of the Hikma AG product and 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.

We also granted Hikma 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 September, 2023, Hikma 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.

The Hikma AG product is expected to continue to negatively impact Xyrem and Xywav sales for patients with narcolepsy.

In our settlements with Amneal, Lupin, and Par, we granted each party the right to sell a limited volume of an AG product in the U.S.

1 unchanged sentence

Amneal launched its AG version of high-sodium oxybate in July 2023.

At this time, Amneal has rights to sell a low-single-digit percentage of historical Xyrem sales over each 6-month sales period.

At this time, Lupin and Par have elected not to launch an AG product.

AG products will be distributed through the same REMS as Xywav and Xyrem.

Amneal 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.

Lupin and Par never elected to launch an AG product.

AG products are distributed through the same REMS as Xywav and Xyrem.

We also granted each of Amneal, Lupin and Par a license to launch its own generic sodium oxybate product under its ANDA on or after December 31, 2025, or earlier under certain circumstances, including the circumstance where Hikma elects to launch its own generic product.

If Amneal, Lupin or Par elects to launch its own generic product under such circumstance, it will no longer have the right to sell an AG product.

In September 2025, FDA approved Amneal's generic high-sodium oxybate product.

In November 2025, FDA approved Ascent’s generic high-sodium oxybate product.

In addition, any company commercializing a generic version of high-sodium oxybate would need to establish its own REMS, or join an existing REMS operated by another company.

In the future, we expect our oxybate products to continue to face competition from generic versions of high-sodium oxybate pursuant to settlement agreements we entered into with multiple ANDA filers.

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

In addition, 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.

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

2 unchanged sentences

Entering into agreements with PBMs or similar organizations and payors to ensure patient access has and may continue to result in decreased net prices for some of our products.

Moreover, generic or AG high-sodium oxybate products or branded high-sodium oxybate entrants in narcolepsy, such as Avadel’s Lumryz, have had and may continue to have the effect of changing payor or formulary coverage of Xywav or Xyrem in favor of other products, and indirectly adversely affect sales of Xywav and Xyrem.

In any event, we expect that the approval and launch of AG products or other generic versions of Xyrem or Xywav and the approval and launch of any other sodium oxybate product, such as Avadel’s Lumryz, or alternative product that treats narcolepsy will continue to have a negative impact on, and could have a material adverse effect on, our sales of Xywav and Xyrem and on our business, financial condition, results of operations and growth prospects.

Moreover, generic or AG high-sodium oxybate products or branded high-sodium oxybate entrants in narcolepsy, such as Alkermes’ Lumryz, have had and may continue to have the effect of changing payor or formulary coverage of Xywav or Xyrem in favor of other products, and indirectly adversely affect sales of Xywav and Xyrem.

In any event, we expect that the approval and launch of AG products or other generic versions of Xyrem or Xywav and the approval and launch of any other sodium oxybate product, such as Alkermes’ Lumryz, or alternative product that treats narcolepsy will continue to have a negative impact on, and could have a material adverse effect on, our sales of Xywav and Xyrem and on our business, financial condition, results of operations and growth prospects.

Our financial condition, results of operations and growth prospects are also dependent on our ability to maintain or increase sales of Epidiolex/Epidyolex in the U.S.

1 unchanged sentence

The commercial success of Epidiolex/Epidyolex depends on the extent to which patients and physicians accept and adopt Epidiolex/Epidyolex as a treatment for seizures associated with LGS, DS and TSC, and we do not know whether our or others’ estimates in this regard will be accurate.

Physicians may not prescribe Epidiolex and patients may be unwilling to use Epidiolex/Epidyolex if coverage is not provided or reimbursement is inadequate to cover a significant portion of the cost.

Physicians may not prescribe Epidiolex/Epidyolex and patients may be unwilling to use Epidiolex/Epidyolex if coverage is not provided or reimbursement is inadequate to cover a significant portion of the cost.

Additionally, any negative development for Epidiolex/Epidyolex in the market, in clinical development for additional indications, or in regulatory processes in other jurisdictions, may adversely impact the commercial results and potential of Epidiolex/Epidyolex.

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

For example, in November and December 2022, we received notices from ten ANDA filers that they have each filed with FDA an ANDA for a generic version of Epidiolex.

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

We have settled patent litigation with each of the ten companies seeking to market a generic version of Epidiolex in the U.S.

by granting 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.

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

Thus, significant uncertainty remains regarding the commercial potential of Epidiolex/Epidyolex.

In addition to our neuroscience products and product candidates, we are commercializing a portfolio of oncology products, including Rylaze, Zepzelca, Ziihera, Defitelio and Vyxeos.

An inability to effectively commercialize Rylaze, Zepzelca, Ziihera, Defitelio and Vyxeos and to maximize their potential where possible through successful research and development activities could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

In addition to Xywav, Xyrem and Epidiolex/Epidyolex, we are commercializing a portfolio of oncology products, including Rylaze, Zepzelca, Ziihera, Modeyso, Vyxeos and Defitelio.

An inability to effectively commercialize Rylaze, Zepzelca, Ziihera, Modeyso, Vyxeos and Defitelio and to maximize their potential where possible through successful R&D activities could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

A key aspect of our growth strategy is our continued investment in our evolving and expanding R&D activities.

1 unchanged sentence

In addition to continued investment in our R&D pipeline, we intend to continue to grow our business by acquiring or in-licensing, and developing, including with collaboration partners, additional products and product candidates that we believe are highly differentiated and have significant commercial potential.

Failure to identify and acquire, in-license or develop additional products or product candidates, successfully manage the risks associated with integrating any products or product candidates into our portfolio or the risks arising from anticipated and unanticipated problems in connection with an acquisition or in-licensing, such as the GW Acquisition, could have a material adverse effect on our business, results of operations and financial condition.

Failure to identify and acquire, in-license or develop additional products or product candidates, successfully manage the risks associated with integrating any products or product candidates into our portfolio or the risks arising from anticipated and unanticipated problems in connection with an acquisition or in-licensing, such as the recent Chimerix Acquisition, could have a material adverse effect on our business, results of operations and financial condition.

Our industry has been, and is expected to continue to be, subject to healthcare cost containment and drug pricing scrutiny by regulatory agencies in the U.S.

1 unchanged sentence

If new healthcare policies or reforms intended to curb healthcare costs are adopted or if we experience negative publicity with respect to pricing of our products or the pricing of pharmaceutical drugs generally, the prices that we charge for our products may be affected, our commercial opportunity may be limited and/or our revenues from sales of our products may be negatively impacted.

For example, 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, that could negatively affect our business and financial condition.

For example, 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, that could negatively affect our business and financial condition.

In addition, under the Medicaid Drug Rebate Program, rebates owed by manufacturers are no longer subject to a cap on the rebate amount, which could adversely affect our rebate liability.

Moreover, on May 12, 2025, the White House issued an Executive Order directing federal agencies to pursue MFN pricing for certain prescription drugs, under which U.S.

prices would be indexed to the lowest prices available in select OECD countries and on September 30, 2025, the current administration announced the first of several agreements with major pharmaceutical companies that requires drug manufacturers to offer, through a direct-to-consumer platform, U.S.

patients and 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, in exchange for tariff relief.

The White House is currently seeking voluntary pricing concessions from certain manufacturers, with the potential for administrative action to follow if companies do not engage constructively, creating uncertainty around future pricing and reimbursement that could negatively impact our U.S.

revenues and overall business performance, and also is in the process of implementing or considering various Center for Medicare & Medicaid Innovation models that would rely on MFN reference pricing.

We are also subject to increasing pricing pressure and restrictions on reimbursement imposed by payors.

3 unchanged sentences

or such products may be removed from control under the Controlled Substances Act entirely.

If any of our product candidates receive FDA approval, the Department of Health and Human Services and the U.S.

Drug Enforcement Administration will make a scheduling determination.

or foreign regulatory agencies may request additional information regarding the abuse potential of our products which may require us to generate more clinical or other data than we currently anticipate to establish whether or to what extent the substance has an abuse potential, which could increase the cost, delay the approval and/or delay the launch of that product.

Finally, business practices by pharmaceutical companies, including product formulation improvements, patent litigation settlements, and REMS programs, have increasingly drawn public scrutiny from legislators and regulatory agencies, with allegations that such programs are used as a means of improperly blocking or delaying competition.

If any of our product candidates receive FDA approval, the HHS and the DEA will make a scheduling determination.

This generation of data could increase the cost, delay the approval and/or delay the launch of that product.

In addition, business practices by pharmaceutical companies, including product formulation improvements, patent litigation settlements, and REMS programs, have increasingly drawn public scrutiny from legislators and regulatory agencies, with allegations that such programs are used as a means of improperly blocking or delaying competition.

Government investigations with respect to our business practices, including as they relate to the Xywav and Xyrem REMS, the launch of Xywav, our Xyrem patent litigation settlement agreements or otherwise, could cause us to incur significant monetary charges to resolve these matters and could distract us from the operation of our business and execution of our strategy.

In addition, from June 2020 to May 2022, a number of lawsuits were filed on behalf of purported direct and indirect Xyrem purchasers, alleging that the patent litigation settlement agreements we entered with certain generic companies violate state and federal antitrust and consumer protection laws.

For additional information on these lawsuits and other legal 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.

consumer protection laws.

As of October 2025, we resolved the entirety of the Xyrem Antitrust Litigation.

For additional information on these lawsuits, as well as the settlement agreements with respect thereto and other legal matters, see Note 10, Commitments and Contingencies-Legal Proceedings of the Notes to Consolidated Financial Statements, included in Part IV of this Annual Report on Form 10‑K.

It is possible that additional lawsuits will be filed against us making similar or related allegations.

We cannot predict the outcome of these or potential additional lawsuits;

We cannot predict the outcome of any potential additional lawsuits;

however, if the plaintiffs were to be successful in their claims against us, they may be entitled to injunctive relief or we may be required to pay significant monetary damages.

Moreover, we are, and expect to continue to be, the subject of various claims, legal proceedings, and government investigations apart from those set forth above that have arisen in the ordinary course of business that have not yet been fully resolved and that could

adversely affect our business and the execution of our strategy.

Any of the foregoing risks and uncertainties could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

Finally, the U.S.

government has imposed and may seek to impose additional restrictions on international trade, such as tariffs on goods generally, and pharmaceutical and biological products in particular, imported into the U.S.

In anticipation of the potential for increased tariffs on our products, we have increased inventory levels of our products in the U.S.

We conduct our business globally and have third-party suppliers located outside the U.S., including in the PRC.

In addition, we have a manufacturing and development facility in Athlone, Ireland where we manufacture Xywav and Xyrem, a manufacturing and development facility in Kent Science Park, U.K.

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

While we cannot at this time predict the ultimate impact of such tariffs, we anticipate that our margins could be adversely affected beginning as early as fiscal 2026, depending on the ultimate scope and duration of tariffs imposed.

However, given the volatility and uncertainty regarding the scope and duration of such tariffs and other aspects of U.S.

and foreign government trade policies, the ultimate impact on our operations and financial results remains uncertain and could be significant.

See the risk factor under the heading “ Global trade issues and changes in and uncertainties with respect to trade policies and export regulations, including import and export license requirements, trade sanctions, tariffs and international trade disputes, could increase our costs, reduce the competitiveness of our products and otherwise 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.

The foregoing risks and uncertainties are discussed in greater detail, along with other risks and uncertainties, in “Risk Factors” in Part I, Item 1A.

of this Annual Report on Form 10-K.

Results of Operations

7 unchanged sentences

Intangible asset amortization 654,661 4 % 627,313 3 % 608,284

Intangible asset impairment charge — — % — N/A(1) 133,648

Acquired in-process research and development 10,000 (47) % 19,000 (96) % 444,148

Acquired in-process research and development 947,862 N/A(1) 10,000 (47) % 19,000

Interest expense, net 195,051 (18) % 238,097 (18) % 289,438

1 unchanged sentence

Income tax benefit (272,443) 198 % (91,429) (24) % (119,912)

Equity in loss of investees 1,660 (45) % 3,009 N/A(1) 9,921

Equity in loss of investees 732 (56) % 1,660 (45) % 3,009

_________________________

5 unchanged sentences

Epidiolex/Epidyolex 1,059,197 9 % 972,423 15 % 845,468

Sativex 18,877 (4) % 19,668 17 % 16,825

— — % — N/A(1) 28,844

16,277 (14) % 18,877 (4) % 19,668

Total Neuroscience 2,878,494 7 % 2,698,318 — % 2,707,843

3 unchanged sentences

Vyxeos 146,709 (10) % 162,595 10 % 147,495

Ziihera 1,051 N/A(1) — — % —

Modeyso 48,043 N/A(2) — — % —

Ziihera 24,810 N/A(2) 1,051 N/A(1) —

Total Oncology 1,129,183 2 % 1,111,375 9 % 1,015,254

1 unchanged sentence

Product sales, net 4,021,849 5 % 3,821,164 2 % 3,736,943

High-sodium oxybate AG royalty revenue 217,575 187 % 75,918 N/A(1) —

High-sodium oxybate AG royalty revenue 211,725 (3) % 217,575 187 % 75,918

Other royalty and contract revenues 34,012 13 % 30,211 42 % 21,343

1 unchanged sentence

_________________________

(1) Net product sales of Sativex are included until the date of divestment, October 31, 2025.

(2) Comparison to prior period is not meaningful.

(2) Net product sales of Sunosi U.S.

are included until the date of divestment to Axsome of May 9, 2022.

Product Sales, Net

Xywav product sales increased in 2024 compared to 2023, primarily due to increased sales volumes of 16% and, to a lesser extent, a higher selling price, offset by higher gross to net deductions.

We continue to see Xywav adoption in patients

with narcolepsy driven by educational initiatives around efficacy and the benefit of lowering sodium intake.

Total Revenues

Xywav product sales increased by 12% in 2025 compared to 2024, primarily due to increased sales volumes of 14% and, to a lesser extent, a higher selling price, partially offset by higher gross to net deductions.

We continue to see Xywav adoption in patients with narcolepsy driven by educational initiatives around efficacy and the benefit of lowering sodium intake.

In addition, Xywav product sales were positively impacted by adoption in IH;

Xywav is the only oxybate therapy approved to treat IH and we see continued growth of new prescribers.

Exiting 2024, there were 10,250 patients taking Xywav for narcolepsy and 3,900 taking Xywav for IH, an increase of approximately 8% and 41%, respectively, compared to 2023.

Xywav product sales increased in 2023 compared to 2022, primarily due to increased sales volumes of 28% and, to a lesser extent, a higher selling price.

Exiting 2025, there were 10,950 patients taking Xywav for narcolepsy and 5,225 patients taking Xywav for IH, an increase of approximately 7% and 34%, respectively, compared to 2024.

Xywav product sales increased in 2024 compared to 2023, primarily due to increased sales volumes of 16% and, to a lesser extent, a higher selling price, partially offset by higher gross to net deductions.

Xyrem product sales decreased in 2025 compared to 2024, primarily due to decreased sales volumes of 33%, due to high-sodium oxybate competition and the adoption of Xywav by existing Xyrem patients and higher gross to net deductions, partially offset by a higher selling price.

Xyrem product sales decreased in 2023 compared to 2022, primarily due to decreased sales volumes of 49%, reflecting the adoption of Xywav by existing Xyrem patients and the impact of high-sodium oxybate competition, offset by a higher selling price and lower gross to net deductions.

Xyrem product sales decreased in 2024 compared to 2023, primarily due to decreased sales volumes of 57%, due to high-sodium oxybate competition and the adoption of Xywav by existing Xyrem patients and higher gross to net deductions, partially offset by a higher selling price.

Epidiolex/Epidyolex product sales increased by 9% in 2025 compared to 2024, primarily due to increased sales volumes of 7% due to increased demand, and a higher average selling price.

Epidiolex/Epidyolex product sales increased by 15% in 2024 compared to 2023, primarily due to increased sales volumes of 12% due to increased demand, and, to a lesser extent, geographic expansion and a higher average selling price.

Epidiolex/Epidyolex product sales increased by 15% in 2023 compared to 2022, primarily due to increased sales volumes of 15% due to increased demand and expansion in European markets and, to a lesser extent, a higher average selling price, partially offset by higher gross to net deductions.

Rylaze/Enrylaze product sales increased in 2024 compared to 2023, primarily due to a higher average selling price, partially offset by higher gross to net deductions.

Rylaze sales volumes in 2024 have been negatively impacted due to an update to the COG pediatric treatment protocols for ALL, which impacts the timing of asparaginase administration.

While this had a temporary negative impact on Rylaze product sales in the latter part of 2024, we do not expect it will affect ongoing demand and we still expect our product sales to normalize by early 2025.

Rylaze remains the only therapy available to patients in the U.S.

who have a hypersensitivity reaction to E.

coli-derived asparaginase.

Rylaze product sales increased in 2023 compared to 2022, primarily due to increased sales volumes of 37% and, to a lesser extent, a higher selling price, offset by higher gross to net deductions.

The increased sales volumes reflected the significant unmet patient need for a high-quality, reliable supply of Erwinia asparaginase for patients with ALL.

Zepzelca product sales increased by 11% in 2024 compared to 2023, primarily due to increased sales volumes and a higher selling price, offset by higher gross to net deductions.

Zepzelca product sales increased by 7% in 2023 compared to 2022, primarily due to a higher selling price and increased sales volumes, offset by higher gross to net deductions.

Rylaze/Enrylaze product sales decreased by 2% in 2025 compared to 2024, primarily due to decreased sales volumes of 1% and higher gross to net deductions, partially offset by a higher average selling price.

Updates to pediatric treatment protocols for ALL were implemented in 2024 and impacted Rylaze in 2025.

The protocols have been widely adopted and Rylaze use within the asparaginase class remains broadly stable.

Rylaze product sales increased in 2024 compared to 2023, primarily due to a higher average selling price, partially offset by higher gross to net deductions.

Zepzelca product sales decreased by 4% in 2025 compared to 2024, primarily due to decreased sales volumes, partially offset by a higher selling price and lower gross to net deductions.

Zepzelca product sales have been impacted by increased competition in second-line SCLC and treatment protocol updates delaying progression of first-line limited-stage SCLC patients to the second-line setting.

In October 2025, Zepzelca in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs was approved as a first-line maintenance treatment for adults with ES-SCLC whose disease has not progressed after first-line induction therapy with atezolizumab, carboplatin and etoposide.

Zepzelca product sales increased by 11% in 2024 compared to 2023, primarily due to

increased sales volumes and a higher selling price, offset by higher gross to net deductions.

Defitelio/defibrotide product sales decreased by 8% in 2025 compared to 2024, primarily due to decreased sales volumes, partially offset by the positive impact of foreign exchange rates and a higher average selling price.

Defitelio/defibrotide product sales increased by 18% in 2024 compared to 2023, primarily due to increased sales volumes, and to a lesser extent, a higher average selling price.

Defitelio/defibrotide product sales decreased by 5% in 2023 compared to 2022, primarily due to a decrease in sales volumes, partially offset by a higher selling price.

Vyxeos product sales decreased by 10% in 2025 compared to 2024, primarily due to decreased sales volumes, partially offset by a higher average selling price.

Vyxeos product sales increased by 10% in 2024 compared to 2023, primarily due to increased sales volumes, partially offset by a lower average selling price due to regional mix.

Vyxeos product sales increased by 15% in 2023 compared to 2022, primarily due to increased sales volumes and to a lesser extent, a higher selling price, partially offset by higher gross to net deductions.

We expect product sales, net will increase in 2025 over 2024, primarily driven by growth across our commercial portfolio, offset by a decrease in sales of Xyrem due to the impact of high-sodium oxybate competition.

Royalties and Contract Revenues

Royalties and contract revenues increased in 2024 compared to 2023 and in 2023 compared to 2022 primarily due to royalty revenue received from Hikma on net sales of their high-sodium oxybate AG.

We expect royalties and contract revenues to increase in 2025 compared to 2024, primarily due to increased royalty revenues arising from net sales of high-sodium oxybate AG.

Modeyso product sales were $48.0 million in 2025, following its product launch in August 2025 and Ziihera product sales were $24.8 million in 2025, following product launch in December 2024.

Royalties and contract revenues in 2025 were in line with 2024.

Royalties and contract revenues increased in 2024 compared to 2023, primarily due to royalty revenue received from Hikma on net sales of their high-sodium oxybate AG.

We expect total revenues in 2026 to increase compared to 2025, driven by continued growth in our rare oncology and epilepsy products including Modeyso, Ziihera and Epidiolex/Epidyolex, offset by a reduction in oxybate revenues due to decreased high-sodium AG royalties and Xyrem revenues following the launch of multiple generic high-sodium products.

Cost of Product Sales

Cost of product sales increased in 2024 compared to 2023, due to increased inventory provisions and changes in product mix, offset by a decrease in the fair value step-up expense, of $16.4 million.

Cost of product sales decreased in 2023 compared to 2022, primarily due to a reduction in the fair value step-up expense of $121.9 million and the impact of an expense for past royalties recorded in 2022 in connection with a settlement agreement with Otsuka, partially offset by changes in product mix.

Gross margin as a percentage of net product sales was 88.3% in both 2024 and 2023 and 85.2% in 2022.

The increase in our gross margin percentage in 2023 compared to 2022 was primarily due to the decrease in the fair value step-up expense in 2023 and the impact of the Otsuka royalty expense in 2022.

We expect our cost of product sales to increase in 2025 compared to 2024, primarily driven by changes in product mix.

Cost of product sales increased in 2025 compared to 2024, primarily due to changes in product mix, and to a lesser extent, an increase in the fair value step-up expense, of $12.9 million.

Cost of product sales increased in 2024 compared to 2023, primarily due to increased inventory provisions and changes in product mix, offset by a decrease in the fair value step-up expense, of $16.4 million.

Gross margin as a percentage of net product sales was 87.5% in 2025 and 88.3% in both 2024 and 2023.

The decrease in our gross margin percentage in 2025 compared to 2024 was primarily due to changes in product mix and the increase in the fair value step-up expense in 2025.

We expect our cost of product sales in 2026 to be in line with 2025.

Selling, General and Administrative Expenses

Selling, general and administrative expenses increased in 2025 compared to 2024, primarily due to Xyrem antitrust litigation settlements of $233.5 million, the Avadel litigation settlement of $90.0 million and an increase in compensation-related expenses of $96.7 million, primarily driven by higher headcount and increased share-based compensation expense, increased investment in sales and marketing of $21.9 million in support of our commercial portfolio, and included integration expenses related to the Chimerix Acquisition of $19.4 million.

Selling, general and administrative expenses increased in 2024 compared to 2023, primarily due to increased compensation-related expenses of $72.6 million, primarily driven by higher headcount and increased investment in sales and marketing of $19.3 million, in support of our commercial portfolio and increased litigation costs of $13.6 million, partially offset by costs relating to the impairment of facility assets of $61.7 million and program terminations of $23.5 million incurred in 2023.

Selling, general and administrative expenses decreased in 2023 compared to 2022, primarily due to the loss on

disposal of Sunosi of $40.8 million, restructuring costs of $22.1 million and GW related integration costs of $21.1 million incurred in 2022, together with a reduction in costs related to program terminations of $19.1 million and in compensation related expenses, partially offset by an impairment of facility assets of $61.7 million in 2023.

We expect selling, general and administrative expenses in 2025 to increase compared to 2024, primarily due to investment in our commercial portfolio, including the launch of Ziihera, along with increased compensation-related expenses.

We expect selling, general and administrative expenses in 2026 to decrease compared to 2025, primarily due to the impact of litigation settlement expenses incurred in 2025.

Research and Development Expenses

Research and development expenses consist primarily of costs related to clinical studies and outside services, personnel expenses, milestone expenses and other research and development costs.

R&D expenses consist primarily of costs related to clinical studies and outside services, personnel expenses, milestone expenses and other R&D costs.

Clinical study and outside services costs relate primarily to services performed by clinical research organizations, materials and supplies, and other third party fees.

Personnel expenses relate primarily to salaries, benefits and share-based compensation.

Other research and development expenses primarily include overhead allocations consisting of various support and facilities-related costs.

We do not track fully-burdened research and development expenses on a project-by-project basis.

We manage our research and development expenses by identifying the research and development activities that we anticipate will be performed during a given period and then prioritizing efforts based on our assessment of which development activities are important to our business and have a reasonable probability of success, and by dynamically allocating resources accordingly.

Other R&D expenses primarily include overhead allocations consisting of various support and facilities-related costs.

We do not track fully-burdened R&D expenses on a project-by-project basis.

We manage our R&D expenses by identifying the R&D activities that we anticipate will be performed during a given period and then prioritizing efforts based on our assessment of which development activities are important to our business and have a reasonable probability of success, and by dynamically allocating resources accordingly.

We also continually review our development pipeline projects and the status of their development and, as necessary, reallocate resources among our development pipeline projects that we believe will best support the future growth of our business.

The following table provides a breakout of our research and development expenses by major categories of expense (in thousands):

The following table provides a breakout of our R&D expenses by major categories of expense (in thousands):

Year Ended December 31,

3 unchanged sentences

Milestone expense — 2,500 5,500

Restructuring expenses — — 10,284

Other 85,498 79,703 84,674

Total $ 782,736 $ 884,000 $ 849,658

Research and development expenses increased by $34.3 million in 2024 compared to 2023.

R&D expenses decreased by $101.3 million in 2025 compared to 2024.

Clinical studies and outside services costs decreased in 2025 compared to 2024, primarily due to lower costs related to zanidatamab, as a result of timing of clinical trial activities, JZP385 (essential tremor) following discontinuation of this program and JZP258 (XYLO/DUET) due to the completion of this trial in the first half of 2025, partially offset by the addition of costs relating to Modeyso following the Chimerix Acquisition.

Personnel expenses increased by $29.1 million in 2025 compared to 2024, primarily due to increased compensation related expenses following the Chimerix Acquisition and increased share-based compensation expense.

Other R&D expenses increased by $5.8 million in 2025 compared to 2024 primarily due to the inclusion of integration expenses related to the Chimerix Acquisition of $9.6 million.

R&D expenses increased by $34.3 million in 2024 compared to 2023.

Clinical studies and outside services costs increased in 2024 compared to 2023, primarily due to the addition of costs related to clinical programs for zanidatamab, partially offset by a reduction in costs related to JZP150 (post-traumatic stress disorder) and JZP385.

Personnel expenses increased by $32.6 million in 2024 compared to 2023, primarily due to increased compensation related expenses in support of our development programs.

Research and development expenses increased by $259.2 million in 2023 compared to 2022.

Clinical studies and outside services costs increased in 2023 compared to 2022, primarily due to the addition of costs related to clinical programs for zanidatamab, and, to a lesser extent, JZP385 and JZP441, partially offset by a reduction in costs related to JZP458 (Rylaze).

Personnel expenses increased by $34.7 million in 2023 compared to 2022, primarily due to increased headcount in support of our development programs.

Milestone expenses of $5.5 million in 2023 primarily related to a milestone expense of $5.0 million under our collaboration and license agreement with Werewolf.

Milestone expenses of $6.3 million in 2022 primarily related to a milestone expense of $5.0 million made under our asset purchase and collaboration agreements with Redx.

We incurred restructuring costs of $10.3 million in 2022.

For 2025, we expect that our research and development expenses will decrease compared to 2024, primarily driven by a reduction in clinical studies and outside services costs relating to JZP385 and continued portfolio prioritization.

For 2026, we expect that our R&D expenses will increase compared to 2025, primarily driven by an increase in clinical studies and outside service costs relating to zanidatamab, for both ongoing and new studies, dordaviprone, due to the inclusion of a full year’s expenses, and preclinical and early clinical programs.

Intangible Asset Amortization

Intangible asset amortization increased by $19.0 million in 2024 compared to 2023, primarily due to the foreign exchange impact on our sterling-denominated intangible assets.

Intangible asset amortization for 2023 was in line with 2022.

Intangible asset amortization in 2025 is expected to be broadly in line with 2024.

Intangible asset amortization increased by $27.3 million in 2025 compared to 2024, and increased by $19.0 million in 2024 compared to 2023, primarily due to the impact of foreign exchange on our sterling-denominated intangible assets.

Acquired In-Process Research and Development

Acquired IPR&D expense in 2025 represents the value allocated to Modeyso in the Chimerix Acquisition of $905.4 million and the upfront payment made in connection with our global license agreement with Saniona of $42.5 million.

Acquired IPR&D expense in 2024 related to the upfront payment made in connection with our asset purchase agreement with Redx of $10.0 million.

Acquired IPR&D expense in 2023 primarily related to the upfront payment made in connection with our licensing and collaboration agreement with Autifony of $18.0 million.

Acquired IPR&D expense in 2022 primarily related to the upfront payments made in connection with our licensing and collaboration agreements with Zymeworks and Werewolf of $375.0 million and $15.0 million, respectively, and our licensing agreement with Sumitomo of $50.0 million.

Intangible Asset Impairment Charge

In 2022, we recorded an acquired IPR&D asset impairment charge of $133.6 million as a result of the decision to discontinue our nabiximols program.

Interest Expense, Net

Interest expense, net decreased by $43.0 million in 2025 compared to 2024, primarily due to lower interest expense on the Tranche B-2 Dollar Term Loans, partially offset by the inclusion of interest expense on our 2030 Notes for the full year in 2025 and lower interest income as a result of lower cash reserves due to the Chimerix Acquisition and reduced interest rates.

Interest expense, net decreased by $51.3 million in 2024 compared to 2023, primarily due to higher interest income on investments driven by our increased deposits and higher interest rates and lower interest expense on the Tranche B-2 Dollar Term Loans following the 2024 repricings described under “Liquidity and Capital Resources—Credit Agreement” below, offset by the inclusion of interest expense on our 2030 Notes.

Interest expense, net increased by $1.2 million in 2023 compared to 2022, primarily driven by higher interest rates on our outstanding term loan borrowings, partially offset by higher interest income on investments and the inclusion of interest expense on the now repaid Euro Term Loan, in 2022.

We expect interest expense, net to decrease in 2025 compared to 2024 primarily due to lower interest expense following the voluntary repayment of $750.0 million on our Tranche B-2 Dollar Term Loans in January 2025, partially offset by lower interest income and interest expense on the 2030 Notes.

For further information on this please refer to Liquidity and Capital Resources.

Foreign Exchange (Gain) Loss

The foreign exchange (gain) loss is primarily related to the translation of sterling and euro-denominated net monetary liabilities, primarily intercompany balances, held by subsidiaries with a U.S.

dollar functional currency and related foreign exchange forward contracts not designated as hedging instruments.

Income Tax Benefit

Our income tax benefit was $91.4 million, $119.9 million and $158.6 million in 2024, 2023 and 2022, respectively, relating to tax arising on income or losses in Ireland, the U.K., the U.S.

Our income tax benefit was $272.4 million, $91.4 million and $119.9 million in 2025, 2024 and 2023, respectively.

Our income tax benefit in 2025 arose primarily due to the reversal of a valuation allowance against certain U.S.

federal and state deferred tax assets acquired through the Chimerix Acquisition.

Apart from the reversal of the valuation allowance, the income tax benefit related to tax arising on income or losses in Ireland, the U.K., the U.S.

and certain other foreign jurisdictions, offset by deductions on subsidiary equity, patent box benefits, foreign derived intangible income benefits and originating tax credits.

Our income tax benefit in 2024 decreased compared to 2023 primarily due to the change in income mix across jurisdictions, partially offset by patent box benefits.

Our income tax benefit in 2023 decreased compared to 2022 primarily due to pretax losses from payments for acquired IPR&D made in 2022 and the impact of the 2022 impairment of our acquired IPR&D asset as a result of the decision to discontinue our nabiximols program, partially offset by the change in income mix across jurisdictions.

Equity in Loss of Investees

Equity in loss of investees relates to our share in the net loss of companies in which we have made investments accounted for under the equity method of accounting.

Liquidity and Capital Resources

2 unchanged sentences

During 2025, 2024 and 2023, we generated cash flows from operations of $1.4 billion, $1.4 billion and $1.1 billion, respectively, and we expect to continue to generate positive cash flow from operations which we expect will enable us to operate our business and de-lever our balance sheet over time.

Since the closing of the acquisition of GW in May 2021, we have fully repaid our Euro Term Loan.

Since the closing of the GW Acquisition in May 2021, we have fully repaid our Euro Term Loan.

With respect to our Tranche B-2 Dollar Term Loans, we have made voluntary repayments of $1.1 billion, $300.0 million in September 2022 and $750.0 million in January 2025, along with mandatory repayments of $139.5 million.

2 unchanged sentences

For a more detailed description of our debt arrangements, including information relating to our scheduled maturities with respect to our long-term debt see Note 11, Debt, of the Notes to Consolidated Financial Statements, included in Part IV of this Annual Report on Form 10‑K .

This substantial level of debt could have important consequences to our business, including, but not limited to the factors set forth in in Part I, Item 1A “Risk Factors” o f this Annual Report on Form 10‑K under the headi ng “We have incurred substantial debt, which could impair our flexibility and access to capital and adversely affect our financial position, and our business would be adversely affected if we are unable to service our debt obligations.”

We believe that our existing cash, cash equivalents and investments balances, cash we expect to generate from operations and funds available under our Amended Revolving Credit Facility will be sufficient to fund our operations and to meet our

existing obligations for the foreseeable future.

This substantial level of debt could have important consequences to our business, including, but not limited to the factors set forth in Part I, Item 1A “Risk Factors” o f this Annual Report on Form 10‑K under the headi ng “ We have incurred substantial debt, which could impair our flexibility and access to capital and adversely affect our financial position, and our business would be adversely affected if we are unable to service our debt obligations.

The adequacy of our cash resources depends on many assumptions, including primarily our assumptions with respect to product sales and expenses, as well as the other factors set forth in “Risk Factors” in Part I, Item 1A of this Annual Report on Form 10‑K under the headings “Risks Related to our Lead Products and Product Candidates” and “To continue to grow our business, we will need to commit substantial resources, which could result in future losses or otherwise limit our opportunities or affect our ability to operate and grow our business.” Our assumptions may prove to be wrong or other factors may adversely affect our business, and as a result we could exhaust or significantly decrease our available cash resources, and we may not be able to generate sufficient cash to service our debt obligations which could, among other things, force us to raise additional funds and/or force us to reduce our expenses, either of which could have a material adverse effect on our business.

4 unchanged sentences

In addition, we may pursue new operations or continue the expansion of our existing operations.

Accordingly, we expect to continue to opportunistically seek access to additional capital to license or acquire additional products, product candidates or companies to expand our operations or for general corporate purposes.

Raising additional capital could be accomplished through one or more public or private debt or equity financings, collaborations or partnering arrangements.

2 unchanged sentences

Accordingly, we could experience an inability to access additional capital or our liquidity could otherwise be impacted, which could in the future negatively affect our capacity for certain corporate development transactions or our ability to make other important, opportunistic investments.

In addition, under Irish law we must have authority from our shareholders to issue any ordinary shares, including ordinary shares that are part of our authorized but unissued share capital, and we currently have such authorization.

Moreover, as a matter of Irish law, when an Irish public limited company issues ordinary shares to new shareholders for cash, the company must first offer those shares on the same or more favorable terms to existing shareholders on a pro rata basis, unless this statutory pre-emption obligation is dis-applied, or opted out of, by approval of its shareholders.

1 unchanged sentence

This current pre-emption opt-out authority is due to expire in January 2027.

If we are unable to obtain further pre-emption authorities from our shareholders in the future, or otherwise continue to be limited by the terms of new pre-emption authorities approved by our shareholders in the future, our ability to use our unissued share capital to fund in-licensing, acquisition or other business opportunities, or to otherwise raise capital, including at the time we are required to make repurchases of the 2026 Notes, the 2030 Notes and/or the Secured Notes, are required to repay outstanding amounts under the Amended Credit Agreement, or pay cash upon exchange of the 2026 Notes or the 2030 Notes, could likewise be adversely affected.

If we are unable to obtain further share issuance and pre-emption authorities from our shareholders in the future, or otherwise continue to be limited by the terms of new share issuance and pre-emption authorities approved by our shareholders in the future, our ability to use our unissued share capital to fund in-licensing, acquisition or other business opportunities, or to otherwise raise capital, including at the time we are required

to make repurchases of the 2026 Notes, the 2030 Notes and/or the Secured Notes, are required to repay outstanding amounts under the Amended Credit Agreement, or pay cash upon exchange of the 2026 Notes or the 2030 Notes, could likewise be adversely affected or precluded altogether.

In any event, an inability to borrow or raise additional capital in a timely manner and on attractive terms could prevent us from expanding our business or taking advantage of acquisition opportunities and could otherwise have a material adverse effect on our business and growth prospects.

1 unchanged sentence

Furthermore, any equity financing would be dilutive to our shareholders, and could require the consent of the lenders under the Amended Credit Agreement that provides for (i) the Tranche B-2 Dollar Term Loans and Amended Revolving Credit Facility, and the indenture for the Secured Notes for certain financings.

In July 2024, our board of directors authorized the New Repurchase Program.

In July 2024, our board of directors authorized the New Repurchase Program to repurchase ordinary shares having an aggregate purchase price of $500.0 million, exclusive of any brokerage commissions.

Under the New Repurchase Program, which has no expiration date, we may repurchase ordinary shares from time to time by any methods and/or structures permitted by applicable law.

1 unchanged sentence

The New Repurchase Program may be modified, suspended or discontinued at any time without our prior notice.

The New Repurchase Program replaces and supersedes the Old Repurchase Program.

The New Repurchase Program replaces and supersedes the Old Repurchase Program, a share repurchase program to repurchase ordinary shares having an aggregate purchase price of $1.5 billion, exclusive of any brokerage commissions.

In 2025, we spent a total of $125.0 million to repurchase 1.1 million of our ordinary shares, all under the New Repurchase Program, at a purchase price, including commissions, of $109.52 per share.

In 2024, we spent a total of $311.4 million to purchase 2.8 million of our ordinary shares under the repurchase programs at an average total purchase price, including commissions, of $110.06 per share.

The repurchases in 2024 included a total of $150.0 million to repurchase 1.4 million of our ordinary shares, all under the New Repurchase Program, at a purchase price, including commissions, of $109.32 per share and $161.4 million to repurchase 1.5 million of our ordinary shares, all under the Old Repurchase Program, at a purchase price, including commissions, of $110.75 per share.

The repurchases made under the New Repurchase Program in 2024 were effected in privately negotiated transactions with or through one of the initial purchasers of the 2030 Notes concurrently with the pricing of the offering of the 2030 Notes.

In 2023, we spent a total of $269.8 million to purchase 2.1 million of our ordinary shares under the Old Repurchase Program at an average total purchase price, including commissions, of $126.65 per share.

All ordinary shares repurchased were cancelled.

The repurchases made under the New Share Repurchase Program in 2024 were effected in privately negotiated transactions with or through one of the initial purchasers of the 2030 Notes concurrently with the pricing of the offering of the 2030 Notes.

All ordinary shares repurchased were canceled.

As of December 31, 2025, the remaining amount authorized for repurchases under the New Repurchase Program was $225.0 million, exclusive of any brokerage commissions.

6 unchanged sentences

Effect of exchange rates on cash and cash equivalents 6,555 (1,675) 1,137

Net increase in cash and cash equivalents $ 906,554 $ 624,828 $ 290,034

Net increase (decrease) in cash and cash equivalents $ (1,020,965) $ 906,554 $ 624,828

Operating activities

Net cash provided by operating activities decreased by $40.1 million in 2025 compared to 2024, primarily due to the payment of $323.5 million in litigation settlement expenses in 2025, partially offset by cash received from increased sales of our products and the timing of payment of accrued expenses.

Net cash provided by operating activities increased by $303.9 million in 2024 compared to 2023, primarily due to cash received from increased sales of our products, decreased prepaid income taxes and the timing of payment of accrued expenses.

Net cash provided by operating activities decreased by $180.0 million in 2023 compared to 2022, primarily due to an increase in research and development expenses primarily related to zanidatamab, increased prepaid income taxes and increased interest expense on our outstanding term loan borrowings.

Investing activities

Net cash used in investing activities increased by $1.0 billion in 2025 compared to 2024, primarily due to the following:

• $858.1 million outflow related to the net cash paid for the Chimerix Acquisition;

• $108.5 million increase in acquisition of intangible assets primarily related to milestone payments triggered upon FDA approval of Zepzelca in first-line ES-SCLC, Modeyso and Ziihera in BTC;

• $32.5 million increase in upfront payments for acquired IPR&D driven by the $42.5 million payment to Saniona in 2025, offset by the $10.0 million payment to Redx in 2024.

Net cash used in investing activities increased by $345.1 million in 2024 compared to 2023, primarily due to the following:

2 unchanged sentences

• $9.0 million decrease in upfront payments for acquired IPR&D driven by the $18.0 million payment to Autifony in 2023, partially offset by the $10.0 million payment to Redx in 2024.

Net cash used in investing activities decreased by $283.2 million in 2023 compared to 2022, primarily due to the following:

• $425.1 million decrease in upfront payments for acquired IPR&D primarily driven by the $375.0 million, $50.0 million and $15.0 million payments to Zymeworks, Sumitomo and Werewolf, respectively, in 2022, partially offset by the $18.0 million payment to Autifony in 2023;

• $119.1 million net increase in the acquisition of investments, primarily time deposits;

• $53.0 million upfront payment from Axsome in 2022 relating to the Sunosi U.S.

Financing activities

Net cash provided by (used in) financing activities decreased by $893.9 million in 2025 compared to 2024, primarily due to:

• The $750.0 million voluntary repayment on the Tranche B-2 Dollar Term Loan in January 2025;

• Net proceeds from the issuance of the 2030 Notes of $980.8 million in 2024;

partially offset by

• The repayment of the 2024 Notes of $575.0 million in 2024;

• A decrease of $186.4 million in share repurchases;

• An increase of $87.2 million in proceeds from employee equity incentive and purchase plans.

Net cash provided by (used in) financing activities increased by $325.8 million in 2024 compared to 2023, primarily due to:

• An increase of $405.8 million in debt financing due to net proceeds from issuance of the 2030 Notes of $980.8 million, offset by the repayment of the 2024 Notes of $575.0 million;

• Net proceeds from the issuance of the 2030 Notes of $980.8 million in 2024;

partially offset by

• The repayment of the 2024 Notes of $575.0 million in 2024;

• An increase of $41.7 million in share repurchases;

• A decrease of $25.8 million in proceeds from employee equity incentive and purchase plans.

Net cash used in financing activities decreased by $224.2 million in 2023 compared to 2022, primarily due to:

• Repayments of long-term debt of $31.0 million in 2023, compared to $582.0 million in 2022;

• Share repurchases of $269.8 million in 2023;

• A decrease of $51.6 million in proceeds from employee equity incentive and purchase plans.

Credit Agreement

22 unchanged sentences

• if, as of any date from March 16, 2026 to the 2026 Notes Springing Maturity Date, (x) any 2026 Maturity Indebtedness remains outstanding and (y) the aggregate amount of unrestricted cash of Jazz Pharmaceuticals plc and its subsidiaries is less than an amount equal to 125% of the aggregate principal amount of 2026 Maturity Indebtedness outstanding, then the maturity date for the Amended Revolving Credit Facility will be shortened to the 2026 Notes Springing Maturity Date;

Revolving Facility Maturity Date, then the maturity date for the Amended Revolving Credit Facility will be shortened to February 4, 2028;

• if, as of February 4, 2028, (x) more than $500,000,000 of the Term Loan Indebtedness remains outstanding and (y) the maturity date of such Term Loan Indebtedness is not later than the date that is 91 days after the Amended Revolving Facility Maturity Date, then the maturity date for the Amended Revolving Credit Facility will be shortened to February 4, 2028;

• if, as of the Senior Notes Springing Maturity Date, (x) more than $500,000,000 of the Senior Note Indebtedness remains outstanding and (y) the maturity date with respect to such Senior Note Indebtedness is not later than the date that is 91 days after the Amended Revolving Facility Maturity Date, then the maturity date for the Amended Revolving Credit Facility will be shortened to October 16, 2028.

4 unchanged sentences

2029 Senior Secured Notes

On April 29, 2021, Jazz Securities, a wholly owned subsidiary of Jazz Pharmaceuticals plc, closed the offering of the Secured Notes in a private placement.

On April 29, 2021, Jazz Securities, our wholly owned subsidiary, closed the offering of the Secured Notes in a private placement.

We used the proceeds from the Secured Notes to fund, in part, the cash consideration payable in connection with the GW Acquisition.

3 unchanged sentences

The Secured Notes and related guarantees are secured by a first priority lien (subject to permitted liens and certain other exceptions), equally and ratably with the Amended Credit Agreement, on the collateral securing the Amended Credit Agreement.

Some or all of the Secured Notes, may be redeemed at any time and from time to time at a specified redemption prices, plus accrued and unpaid interest, if any, to, but excluding, to the redemption date.

Some or all of the Secured Notes may be redeemed at any time and from time to time at a specified redemption prices, plus accrued and unpaid interest, if any, to, but excluding, the redemption date.

In addition, Jazz Securities may redeem all but not part of the Secured Notes at its option at any time in connection with certain tax-related events at a price equal to 100% of the principal amount of the Secured Notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding, the redemption date.

8 unchanged sentences

The 2030 Notes mature on September 15, 2030, unless earlier exchanged, redeemed or repurchased.

dissolution or the delisting of our ordinary shares from any of The New York Stock Exchange, The Nasdaq Global Market, The Nasdaq Global Select Market or The Nasdaq Capital Market (or any of their respective successors).

The holders of the 2030 Notes have the ability to require us to repurchase all or a portion of their 2030 Notes for cash at a fundamental change repurchase price equal to 100% of the principal amount of the notes to be repurchased, plus accrued and unpaid interest to, but excluding, the fundamental change repurchase date in the event we undergo a fundamental change (as defined in the indenture related to the 2030 Notes), such as specified change of control transactions, our liquidation or dissolution or the delisting of our ordinary shares from any of The New York Stock Exchange, The Nasdaq Global Market, The Nasdaq Global Select Market or The Nasdaq Capital Market (or any of their respective successors).

Additionally, the terms and covenants in the indenture related to the 2030 Notes include certain events of default after which the 2030 Notes may be due and payable immediately.

2 unchanged sentences

The 2030 Notes are exchangeable at an initial exchange rate of 6.5339 ordinary shares per $1,000 principal amount of 2030 Notes, which is equivalent to an initial exchange price of approximately $153.05 per ordinary share.

Upon exchange of the 2030 Notes, we will pay cash up to the aggregate principal amount of the 2030 Notes to be exchanged and pay or deliver, as the case may be, cash, ordinary shares or a combination of cash and ordinary shares, at our election, in respect of the remainder, if any, of our exchange obligation in excess of the aggregate principal amount of the 2030 Notes being exchanged.

if any, of our exchange obligation in excess of the aggregate principal amount of the 2030 Notes being exchanged.

The exchange rate is subject to adjustment in some events but will not be adjusted for any accrued and unpaid interest.

16 unchanged sentences

Prior to March 15, 2026, the 2026 Notes will be exchangeable only upon satisfaction of certain conditions and during certain periods, and thereafter, at any time until the close of business on the second scheduled trading day immediately preceding the maturity date.

In 2017, Jazz Investments completed a private placement of $575.0 million principal amount of 2024 Notes.

We used the net proceeds from this offering to repay $500.0 million in outstanding loans under the Initial Revolving Credit Facility and to pay related fees and expenses.

We used the remainder of the net proceeds for general corporate purposes.

Interest on the 2024 Notes was payable semi-annually in cash in arrears on February 15 and August 15 of each year, beginning on February 15, 2018, at a rate of 1.50% per year.

The 2024 Notes were exchangeable at an initial exchange rate of 4.5659 ordinary shares per $1,000 principal amount of 2024 Notes, which was equivalent to an initial exchange price of approximately $219.02 per ordinary share.

On August 15, 2024, the maturity date for the 2024 Notes, we repaid the $575.0 million aggregate principal amount, plus accrued and unpaid interest thereon.

Contractual Obligations

2 unchanged sentences

For information relating to our scheduled maturities with respect to our long-term debt and our lease liabilities see Note 11 Debt and Note 12 Leases, respectively, and for information relating to our noncancelable purchase commitments due within one year see Note 13 Commitments and Contingencies, included in the Notes to Consolidated Financial Statements, included in Part IV of this Annual Report on Form 10‑K.

Our long-term noncancelable purchase commitments were $31.7 million at December 31, 2024, primarily related to agreements with third party manufactures.

Our long-term noncancelable purchase commitments were $30.6 million at December 31, 2025, primarily related to agreements with third party manufacturers.

We also have potential future milestone payments or royalty obligations to third parties under asset purchase, product development, license and other agreements as the timing and likelihood of such milestone payments are not known, and, in the case of royalty obligations, as the amount of such obligations are not estimable.

Our contingent obligations to third parties, in the form of development, regulatory and sales-based milestone payments, as of December 31, 2024 included $1,362.5 million under our license and collaboration agreement with Zymeworks, $1,255.0 million under our global license and collaboration agreement with Werewolf, $1,090.0 million under our license agreement with Sumitomo, $1,065.0 million under our asset purchase agreements with Redx, $752.5 million under our license and collaboration agreement with Autifony, $581.0 million under our amended license agreement with PharmaMar, $375.0 million under the asset purchase and exclusive license agreement with SpringWorks Therapeutics, Inc., $260.0 million in connection with our acquisition of Cavion, $155.5 million under our license agreement with Ligand, and $492.4 million related to other agreements.

Our contingent obligations to third parties, in the form of development, regulatory and sales-based milestone payments, as of December 31, 2025 included $1,362.5 million under our license and collaboration agreement with Zymeworks, $1,255.0 million under our global license and collaboration agreement with Werewolf, $1,065.0 million under our asset purchase agreements with Redx, $992.5 million under our global license agreement with Saniona, $752.5 million under our license and collaboration agreement with Autifony, $531.0 million under our amended license agreement with PharmaMar, $375.0 million under the asset purchase and exclusive license

agreement with SpringWorks Therapeutics, Inc., $312.0 million and $260.0 million in connection with our acquisitions of Chimerix and Cavion, respectively, and $1,542.4 million related to other agreements.

Critical Accounting Policies and Significant Estimates

24 unchanged sentences

Total items deducted from gross product sales were $1,468.1 million, $1,238.2 million and $1,019.3 million, or 26.7%, 24.5% and 21.4% as a percentage of gross product sales, in 2025, 2024 and 2023, respectively.

Included in these amounts are immaterial adjustments related to prior-year sales due to changes in estimates.

Included in these amounts are adjustments related to prior-year sales due to changes in estimates.

We are subject to rebates on sales made under governmental managed-care pricing programs and commercial payor contracts in the U.S.

8 unchanged sentences

Rebates were $1,038.0 million, $820.9 million and $651.2 million, or 18.9%, 16.2% and 13.7% as a percentage of gross product sales, in 2025, 2024 and 2023, respectively.

Rebates as a percentage of gross product sales in 2024 increased compared to 2023, primarily due to higher rebate rates with commercial payors.

Rebates as a percentage of gross product sales in 2023 were in line with 2022.

Rebates as a percentage of gross product sales are expected to increase in 2025 compared to 2024, primarily due to higher rebate rates in commercial payor contracts.

The increase in rebates as a percentage of gross product sales in 2025 and 2024 was primarily due to higher rebate rates with commercial payors.

Sales returns

3 unchanged sentences

Sales returns were $6.2 million, $15.9 million and $2.5 million, or 0.1%, 0.3% and 0.1% as a percentage of gross product sales in 2025, 2024 and 2023, respectively.

Sales returns as a percentage of gross product sales are not expected to change materially in 2025 compared to 2024.

We participate in chargeback programs with a number of entities, principally Federal Supply Schedule, Group Purchasing Organizations, and other public parties, under which pricing on products below wholesalers’ list prices is provided to participating entities.

These entities purchase product through wholesalers at the contract price and the wholesalers charge back to us the difference between their acquisition cost and the lower negotiated price.

We record the difference as allowances

against accounts receivable.

We record the difference as allowances against accounts receivable.

We determine our estimate of the chargebacks provision primarily based on historical experience on a product and program basis, current contract prices under the chargeback programs and channel inventory data.

Chargebacks were $233.3 million, $212.4 million and $185.9 million, or 4.2%, 4.2% and 3.9% as a percentage of gross product sales in 2025, 2024 and 2023, respectively.

Chargebacks as a percentage of gross product sales increased in 2024 compared to 2023, primarily due to higher chargeback utilization.

Chargebacks as a percentage of gross product sales in 2025 were in line with 2024.

Chargebacks as a percentage of gross product sales increased in 2024 compared to 2023, primarily due to higher chargeback utilization.

Chargebacks as a percentage of gross product sales are not expected to change materially in 2025 compared to 2024.

Discounts and distributor fees

7 unchanged sentences

Discounts and distributor fees were $190.6 million, $189.1 million and $179.7 million, or 3.5%, 3.7% and 3.8% as a percentage of gross product sales in 2025, 2024 and 2023, respectively.

Discounts and distributor fees as a percentage of gross product sales in 2024 were in line with 2023.

Discounts and distributor fees as a percentage of gross product sales in 2023 were broadly in line with 2022.

Discounts and distributor fees as a percentage of gross product sales are not expected to change materially in 2025 compared to 2024.

Discounts and distributor fees as a percentage of gross product sales in 2025 were in line with 2024 and 2023.

Acquisitions and Valuation of Intangibles

28 unchanged sentences

Impairment of Intangible Assets

Finite-lived intangible assets consist primarily of purchased developed technology and are amortized on a straight-line basis over their estimated useful lives, which range from seven to sixteen years.

Finite-lived intangible assets consist of purchased developed technology and are amortized on a straight-line basis over their estimated useful lives, which range from four to sixteen years.

The estimated useful lives associated with intangible assets are consistent with the estimated lives of the products and may be modified when circumstances warrant.

11 unchanged sentences

We did not recognize an impairment charge related to our intangible assets in 2025, 2024 or 2023.

In 2022, we recorded an acquired IPR&D asset impairment charge of $133.6 million as a result of the decision to discontinue our nabiximols program.

Please refer to Note 9, Goodwill and Intangible Assets, of the Notes to Consolidated Financial Statements included in Part IV of this Annual Report on Form 10‑K, for further information about our intangible assets and the remaining useful lives of our finite-lived intangible assets as of December 31, 2025.

24 unchanged sentences

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 7. Management’s Discussion and Analysis