What changed in this filing

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Item 1. Business

2026-02-24 compared with 2025-02-25 · 154 added, 149 removed, 468 unchanged (39% of the section changed)

At Harmony, we are cultivating a differentiated neuroscience company, rooted in innovation and driven by a commitment to addressing the unmet needs of patients living with neurological diseases.

To date, we have focused on rare neurological diseases with a growing portfolio now spanning sleep/wake, neurobehavioral, and rare epilepsy, and we are harnessing scientific insights and pioneering approaches to advance meaningful treatments that help patients thrive.

We are cultivating a differentiated neuroscience company, rooted in innovation and driven by a commitment to addressing the unmet needs of patients living with neurological diseases.

To date, we have focused on rare neurological diseases with a growing portfolio now spanning sleep/wake, rare epilepsy, and neurobehavioral and we are harnessing scientific insights and pioneering approaches to advance meaningful treatments that help patients thrive.

In July 2017, we entered into a License Agreement (as amended, the “2017 LCA”) with Bioprojet Société Civile de Recherche (“Bioprojet”) whereby we acquired the exclusive right to commercialize the pharmaceutical compound pitolisant.

Our lead product, WAKIX® (pitolisant) (“WAKIX”), is a first-in-class therapy with a novel mechanism of action designed to enhance histamine signaling in the brain by binding to H 3 receptors.

Since its initial FDA approval in 2019 for excessive daytime sleepiness (“EDS”) in adult patients with narcolepsy and subsequent approvals for cataplexy in adult patients in 2020 and EDS in pediatric patients six years and older in 2024, WAKIX has continued to reshape the treatment landscape for narcolepsy and remains the only FDA-approved treatment for narcolepsy that is not scheduled as a controlled substance by the U.S.

Since its initial FDA approval in 2019 for excessive daytime sleepiness (“EDS”) in adult patients with narcolepsy and subsequent approvals for cataplexy in adult patients in 2020, EDS in pediatric patients six years and older in 2024 and cataplexy in pediatric patients six years and older in 2026, WAKIX has continued to reshape the treatment landscape for narcolepsy and remains the only FDA-approved treatment for narcolepsy that is not scheduled as a controlled substance by the U.S.

Drug Enforcement Administration (“DEA”).

Beyond narcolepsy, we have taken a mechanistic-based approach to expanding the reach of pitolisant, identifying idiopathic hypersomnia (“IH”) as a potential next indication in its lifecycle.

In the fourth quarter of 2024, we submitted a supplemental New Drug Application (“sNDA”) for pitolisant in IH based on a comprehensive evaluation of data from our INTUNE study and additional sources.

In February 2025, we received a Refusal to File letter from the FDA for pitolisant in IH.

We are also advancing late-stage clinical programs exploring pitolisant in Prader-Willi syndrome (“PWS”) and myotonic dystrophy type 1 (“DM1”) and continue to grow our impact in other rare neurological diseases.

In July 2022, we entered into the 2022 LCA with Bioprojet whereby we obtained exclusive rights to manufacture, develop and commercialize one or more next generation pitolisant based products in the United States and Latin America.

Beyond narcolepsy, we have taken a mechanistic-based approach to expanding the reach of pitolisant, advancing late-stage clinical programs exploring pitolisant in idiopathic hypersomnia (“IH”), Prader-Willi syndrome (“PWS”) and myotonic dystrophy type 1 (“DM1”) and continue to grow our impact in other rare neurological diseases.

In July 2022, we entered into a License and Commercialization Agreement with Bioprojet (the “2022 LCA”) whereby we obtained exclusive rights to manufacture, develop and commercialize one or more next generation pitolisant based products in the United States and Latin America.

Two of the next generation formulations, pitolisant Gastro-Resistant (“Pitolisant GR”) and pitolisant High-Dose (“Pitolisant HD”) are currently in clinical development.

Along with nurturing the growth of our original pipeline, our innovation strategy includes targeted business development that strengthens our foundation and strategically extends our patient reach as we look to expand our portfolio to new diseases beyond histaminergic science.

In October 2023, we acquired Zynerba Pharmaceuticals, Inc.

(“Zynerba”), adding global rights to develop, manufacture and commercialize ZYN-002, a pharmaceutically manufactured 100% synthetic, patent protected permeation enhanced cannabidiol gel , to our neurobehavioral franchise.

With a Phase 3 registrational trial underway for Fragile X syndrome (“FXS”) and plans to initiate a Phase 3 registrational trial in 22q deletion syndrome (“22q”) in 2025, we are poised to deliver new treatment possibilities for patients with neurobehavioral conditions.

In April 2024, we expanded into orexin science through a sublicense agreement with Bioprojet for an orexin 2 receptor agonist (“BP1.15205”) in preclinical development for narcolepsy and other potential indications.

Under the sublicense agreement we obtained the exclusive right to develop, manufacture and commercialize BP1.15205 in the United States and Latin American territories, which are rights originally licensed from Teijin Pharma, the innovator of BP1.15205.

Under the Sublicense, we obtained the exclusive right to develop, manufacture and commercialize BP1.15205 in the United States and Latin American territories, which are rights originally licensed from Teijin Pharma, the innovator of BP1.15205.

We further broadened our portfolio into rare epilepsy with the acquisition of Epygenix Therapeutics, Inc., adding global rights to develop, manufacture and commercialize EPX-100, a serotonin (5HT-2) receptor agonist , and EPX-200, a selective 5HT-2C agonist.

EPX-100 is in Phase 3 registrational trials for Dravet Syndrome (“DS”) and Lennox-Gastaut Syndrome (“LGS”), and EPX-200 is in the pre-IND phase for developmental and epileptic encephalopathies (“DEEs”).

EPX-100 is in two Phase 3 registrational trials, one each for Dravet Syndrome (“DS”) and Lennox-Gastaut Syndrome (“LGS”), and EPX-200 is in the pre-IND phase for developmental and epileptic encephalopathies (“DEEs”).

In June 2025, we entered into a research collaboration, option and license agreement (the “CiRC Agreement”) with a related party, CiRC Biosciences, Inc.

Under this agreement, Harmony and CiRC will collaborate on the research and development of two discovery-stage candidates, CBS105 for treatment-resistant narcolepsy and CBS104 for refractory epilepsy (together the “Candidates”), using cell replacement therapy for the treatment of refractory epilepsies and treatment-resistant narcolepsy.

Our innovative portfolio of assets reflects our dedication to novel science, innovative therapies and excellence in delivering these treatments to patients with serious medical conditions who have few or no available options.

Our operations are conducted by our wholly owned subsidiaries, Harmony Biosciences, LLC and Harmony Biosciences Management, Inc., formerly known as Zynerba prior to July 1, 2024 .

Our operations are conducted by our wholly owned subsidiaries, Harmony Biosciences, LLC and Harmony Biosciences Management, Inc.

Commercial Product

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WAKIX (pitolisant).

Pitolisant was developed by Bioprojet and approved by the EMA in 2016 for the treatment of narcolepsy in adult patients with or without cataplexy and in 2021 for the treatment of EDS in adult patients with obstructive sleep apnea.

We acquired an exclusive license to develop, manufacture and commercialize pitolisant in the United States pursuant to our license agreement with Bioprojet (as amended, the “2017 LCA”) in July 2017.

Pitolisant was developed by Bioprojet and approved by the European Medicines Agency (the “EMA”) in 2016 for the treatment of narcolepsy in adult patients with or without cataplexy and in 2021 for the treatment of EDS in adult patients with obstructive sleep apnea.

We acquired an exclusive license to develop, manufacture and commercialize pitolisant in the United States pursuant to the 2017 LCA.

Pitolisant was granted Orphan Drug designation for the treatment of narcolepsy by the FDA in 2010.

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In October 2020, WAKIX was approved by the FDA for the treatment of cataplexy in adult patients with narcolepsy.

WAKIX was approved by the FDA for treatment of EDS and cataplexy in patients six years and older in 2024 and 2026, respectively.

WAKIX represents a novel approach to narcolepsy treatment.

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● WAKIX is not a stimulant.

Stimulants are one of the most commonly prescribed treatments for patients with narcolepsy and have the potential for abuse so their use must be considered carefully by HCPs and patients.

Stimulants are one of the most commonly prescribed treatments for patients with narcolepsy and have the potential for abuse so their use must be considered carefully by health care providers (“HCPs”) and patients.

Unlike stimulants, in clinical trials, WAKIX showed no evidence for the development of drug tolerance or withdrawal symptoms.

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We believe that pitolisant’s ability to regulate histamine and histaminergic signaling gives it the potential to provide therapeutic benefit in other disorders that are mediated through the H 3 receptor and histamine signaling and offers a portfolio in a product opportunity.

We have continued to pursue label expansion of WAKIX in narcolepsy and seek new indications in rare neurological disease patient populations that have EDS as a prominent symptom, along with other symptoms mediated by CNS histamine signaling including:

Idiopathic Hypersomnia

IH is a central disorder of hypersomnolence resulting in sleep-wake state instability.

It is a rare and chronic neurological disease that is characterized by EDS despite sufficient or even long sleep time.

Based on insurance claims data, the number of patients diagnosed with IH in the US ranges from 30,000 to 40,000.

Pitolisant received orphan drug designation by the FDA for the treatment of IH in September 2023 and Fast Track designation for the treatment of IH in November 2023.

In April 2022, we initiated a Phase 3 registrational trial, the INTUNE Study, to evaluate the efficacy and safety of pitolisant in adult patients with IH.

We completed enrollment in the INTUNE study in May 2023 and we announced topline data in October 2023.

Topline study results include:

● Approximately 83% of patients who completed the 8-week open-label treatment period with pitolisant were responders (as defined by a decrease on the ESS of ≥3 points) and experienced a robust clinical response, with an average ESS change from baseline of – 9.4 points.

● A positive trend favoring pitolisant was observed during the 4-week double-blind randomized withdrawal period, however no statistically significant difference was observed between pitolisant and placebo groups on ESS, the primary endpoint.

● Positive trends favoring pitolisant were also observed across additional prespecified endpoints including the IH Severity Scale, which approached statistical significance, as well as on the Sleep Inertia Questionnaire.

● Approximately 88% of patients in the Double-Blind Randomized Withdrawal Phase continued into a long-term extension study, which is ongoing.

● The safety and tolerability profile of pitolisant in adult patients with idiopathic hypersomnia was consistent with the established safety profile of pitolisant and no new safety signals were observed.

While the primary endpoint did not meet statistical significance, we believe the totality of the data showed favorable numerical trends for pitolisant in the treatment of adult patients with IH.

We met with the FDA in March 2024 to discuss the path forward for IH and submitted an sNDA during the fourth quarter of 2024 based on the totality of the data obtained from the INTUNE study and other sources.

In February 2025, we received a Refusal to File letter from the FDA for pitolisant in IH.

IH is a rare central disorder of hypersomnolence characterized by EDS, non-refreshing sleep and sleep inertia.

There are approximately 80,000 patients with IH in the U.S., with approximately 40,000 diagnosed.

Pitolisant was studied in a phase 3 registrational study for treatment of symptoms of IH.

However, pitolisant did not show a statistically significant difference compared to placebo in the randomized withdrawal period of the study, despite showing clinically meaningful improvements in the initial open-label part of the study.

An sNDA was submitted and we received a refusal-to-file letter in February 2025.

We are currently pursuing IH with Pitolisant HD.

Prader-Willi Syndrome

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Based on the positive signals from our Phase 2 proof-of-concept signal detection clinical trial, an End-of-Phase 2 meeting with the FDA was held in June 2023.

We have aligned with the FDA on the proposed Phase 3 study design to support further investigation of pitolisant as a potential treatment to address the unmet medical need for children, adolescents and adults with PWS experiencing EDS, for which there is currently no approved treatment.

In October 2023, we received FDA feedback regarding our proposed study protocol for the Phase 3 TEMPO study in patients with PWS, which has the potential to serve as a registrational trial and will support our efforts to seek pediatric exclusivity for pitolisant.

approved treatment.

The Phase 3 TEMPO study in patients with PWS has the potential to serve as a registrational trial and will support our efforts to seek pediatric exclusivity for pitolisant.

In February 2024, the FDA granted Orphan Drug designation to pitolisant for the treatment of PWS.

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In addition, in June 2024, the FDA did not approve our sNDA seeking to expand the WAKIX label for the treatment of pediatric patients with cataplexy.

In October 2024, we held a Type A meeting with the FDA to discuss the pediatric cataplexy indication and believe we reached alignment on a path to sNDA resubmission, which is planned for the second quarter of 2025.

In October 2024, we held a Type A meeting with the FDA to discuss the pediatric cataplexy indication and reached alignment on a path to sNDA resubmission, which was submitted in the third quarter of 2025 .

In February 2026, the FDA approved WAKIX for the treatment of cataplexy in pediatric patients six years and older with narcolepsy.

Myotonic Dystrophy Type 1

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Pitolisant Gastro-Resistant and Pitolisant High-Dose

potential to add additional indications and formulations upon the agreement of both parties (see “Strategic Agreements” below).

The 2022 LCA will expand our opportunity in narcolepsy, and potentially other indications mutually agreed upon by the parties.

Pursuant to the 2022 LCA with Bioprojet, we have made progress in the development of two new formulations of pitolisant, pitolisant GR and pitolisant HD.

Both formulations entered into clinical studies in the fourth quarter of 2023.

In July 2022, we entered into the 2022 LCA with Bioprojet whereby we obtained exclusive rights to manufacture, develop and commercialize one or more new products based on pitolisant in the United States and Latin America, with the potential to add additional indications and formulations upon the agreement of both parties (see “Strategic Agreements” below).

The 2022 LCA expands our opportunity in narcolepsy, and potentially other indications mutually agreed upon by the parties.

Pursuant to the 2022 LCA, we have made progress in the development of two new formulations of pitolisant:

Pitolisant GR and Pitolisant HD.

Both formulations entered clinical studies in the fourth quarter of 2023.

We received data from the Pitolisant GR pilot bioequivalence study, which supports further development of Pitolisant GR.

We are on-track to initiate a pivotal bioequivalence study in the first quarter of 2025, with an anticipated data readout in the third quarter of 2025.

Our anticipated PDUFA date for pitolisant GR is in 2026.

We received data from the pitolisant HD pilot pharmacokinetics study in June 2024, which also supports advancing this development program toward Phase 3 registrational trials in narcolepsy and IH.

The formulation optimization and technical operations work is ongoing, with a goal to initiate a Phase 3 registrational study in the fourth quarter of 2025.

A Phase 1b study was conducted to evaluate the safety and tolerability of pitolisant at repeat doses of up to 180mg and the initial results are consistent with the known safety profile of pitolisant and support advancement of the pitolisant HD development program.

Our anticipated PDUFA date for pitolisant HD is in 2028.

Non-provisional patents have been filed for both of these formulations, with the potential for patent protection to the mid-2040’s.

In April 2024, we entered into a sublicense agreement with Bioprojet for BP1.15205, an orexin 2 receptor agonist for the treatment of narcolepsy and other potential indications (the “Sublicense”).

In addition, we completed the a dosing optimization study that supports initiating pitolisant GR at the therapeutic dose of 17.8mg without titration.

We initiated the pivotal bioequivalence study in the first quarter of 2025 and announced positive topline data in November 2025.

The pivotal bioequivalence study confirmed that 17.8mg of pitolisant GR is bioequivalent to existing 17.8mg WAKIX tablets.

The pitolisant GR versus WAKIX area under the curve and Cmax ratios (%) were 108.46 h*ng/mL (90% CI 103.74 – 113.41) and 99.65 ng/mL (90% CI 91.95 – 108.00), respectively.

No new safety or tolerability issues were reported.

Additionally, the topline data from the dosing optimization study of pitolisant GR showed 100% of patients successfully initiated treatment at the therapeutic dose of 17.8mg, eliminating the need for dose titration.

With positive findings from both the pivotal bioequivalence and dosing optimization studies, we are on track to submit a New Drug Application (“NDA”) for Pitolisant GR in early 2026 with a target PDUFA date in the first quarter of 2027.

We received data from the Pitolisant HD pilot pharmacokinetics study in June 2024, which also supports advancing this development program toward pivotal trials.

In addition, we submitted an Investigational New Drug (“IND”) application for pitolisant HD with the FDA to initiate Phase 3 registrational trials in narcolepsy and idiopathic hypersomnia (“IH”) in the fourth quarter of 2025.

After receiving “Study May Proceed” letters from the FDA, the Phase 3 registrational study in narcolepsy, ONSTRIDE1, and the Phase 3 registrational study in IH, ONSTRIDE2, were initiated.

We anticipate topline data from both studies in 2027 and a potential PDUFA date for the Pitolisant HD narcolepsy and IH programs in 2028.

Utility patents have been filed for Pitolisant GR and Pitolisant HD, with the potential for patent protection to the mid-2040s.

We are exploring an opportunity to evaluate of new formulation of pitolisant for the treatment of fatigue in larger CNS indications The histaminergic mechanism of action is uniquely positions to address all three different dimensions of fatigue – physical, emotional and cognition.

We have generated clinical data to support the utility of pitolisant to treat fatigue in the phase 2 proof-of-concept study in DM1, and in a phase 3 study for the treatment of residual sleepiness in patients with obstructive sleep apnea.

We plan to evaluate this new formulation for fatigue in broader indications.

with fatigue in multiple sclerosis (“MS”) as the lead indication, and to explore other potential opportunities such as fatigue in stroke and Parkinson’s disease.

Our current efforts are focused on formulation optimization with new modes of delivery and towards a Phase 1 PK study.

In April 2024, we entered into the Sublicense with Bioprojet for BP1.15205, an orexin 2 receptor agonist for the treatment of narcolepsy and other potential indications.

Under the Sublicense, we have obtained the exclusive right to develop, manufacture and commercialize BP1.15205 in the United States and Latin American territories, which are rights that Bioprojet originally licensed from Teijin Pharma, the innovator of BP1.15205.

We believe the pre-clinical data from BP1.15205 is promising and we plan to file an investigational medicinal product dossier (“IMPD”) with the European Medicines Agency (“EMA”) in mid-2025 and begin first-in-human studies in the second half of 2025.

In June 2025, we announced positive pre-clinical data demonstrating significant wake-promoting and cataplexy-suppressing effects in a standard transgenic mouse model of narcolepsy type 1and presented safety data from the three-month GLP toxicity studies in two different species.

We filed an investigational medicinal product dossier (“IMPD”) with the EMA and began first-in-human studies in the fourth quarter of 2025 and are on-track to receive clinical PK data in mid-2026.

In August 2021, we acquired HBS-102, a Melanin-concentrating hormone receptor type 1 (MCHR1) antagonist previously developed as CSTI-100/ALB-127258(a)/ALB-127258 (the “Compound”), along with intellectual property and other assets related to the development, manufacture, and commercialization of the Compound from ConSynance Therapeutics, Inc.

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The final report was received during the third quarter of 2024 and the results are consistent with the expected results.

In addition, a 13-week toxicology study has been completed, and we believe the preliminary results are encouraging .

Neurobehavioral Franchise

We are currently seeking the following indications for our product candidate, ZYN-002, a pharmaceutically manufactured 100% synthetic, patent protected permeation enhanced cannabidiol gel:

Fragile X Syndrome

FXS is a rare genetic disorder that is the leading known cause of both inherited intellectual disability and autism spectrum disorder, affecting 1 in 3,600 to 4,000 males and 1 in 4,000 to 6,000 females.

The disorder negatively affects synaptic function, plasticity and neuronal connections, and results in a spectrum of intellectual disabilities and behavioral symptoms, such as social avoidance and irritability.

There are approximately 80,000 people in the United States and approximately 121,000 people in the European Union and UK living with FXS.

The total addressable market in the United State alone is estimated to be approximately 25,000 people.

There is a significant unmet medical need in patients living with FXS as there are currently no FDA approved treatments for this disorder.

ZYN-002 is currently in a Phase 3 registrational trial, the RECONNECT study, designed to evaluate the safety and efficacy of ZYN002 in FXS .

Topline data from our ZYN-002 Phase 3 study is anticipated in the third quarter of 2025.

ZYN-002 has patent protection for the treatment of FXS until 2038.

22q Deletion Syndrome

22q is a disorder caused by a small missing piece on the long arm of the 22nd chromosome.

The deletion occurs near the middle of the chromosome at a location designated q11.2.

It is considered a mid-line condition, with physical

symptoms including characteristic palate abnormalities, heart defects, immune dysfunction, and esophageal / GI issues, as well as debilitating neuropsychiatric and behavioral symptoms, including anxiety, social withdrawal, ADHD, cognitive impairment and autism spectrum disorder.

It is estimated that 22q occurs in one in 4,000 live births, suggesting that there are approximately 80,000 people living with 22q in the United States and 129,000 people living with 22q in the European Union and the UK.

Patients with 22q deletion syndrome are managed by multidisciplinary care providers, and there are currently no FDA approved treatments for this disorder.

An open-label phase 2 proof-of-concept study conducted by Zynerba showed positive signals for ZYN-002 in the treatment of behavioral symptoms associated with 22q.

We plan to initiate a Phase 3 registrational study in 22q deletion syndrome in 2025.

In addition, a 13-week toxicology study has been completed, and we believe the results are encouraging .

We are evaluating HBS-102 in other pre-clinical experiments for additional potential indications.

Rare Epilepsy Franchise

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We believe the total addressable market for EPX-100 among patients with LGS is approximately 35,000 people based on an estimated current LGS prevalence of approximately 48,000 cases and 44,000 diagnosed LGS cases.

EPX-100 has been granted orphan drug designation by the FDA for treatment of both DS and LGS.

EPX-100 is currently in a Phase 3 registrational clinical trial for DS and we initiated sites for a Phase 3 registrational clinical trial in patients with LGS in the fourth quarter of 2024.

EPX-100 has been granted orphan drug designation and rare pediatric disease designation by the FDA for treatment of both DS and LGS.

EPX-100 is currently in two Phase 3 registrational clinical trials, one for each of DS (the ARGUS Study) and LGS (the LIGHTHOUSE Study).

In December 2025, we announced initial open-label extension data from the ARGUS Study, which showed clinically meaningful reductions in seizure activity in participants with DS and a favorable benefit-risk profile.

EPX-200 (liquid formulation of lorcaserin).

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EPX-200 is currently in the pre-IND phase.

Neurobehavioral Franchise

In October 2023, we acquired Zynerba Pharmaceuticals, Inc.

(“Zynerba”), adding global rights to develop, manufacture and commercialize ZYN002, which is a pharmaceutically manufactured 100% synthetic, patent protected permeation enhanced cannabidiol gel for transdermal delivery.

In September 2025, we completed a Phase 3 registrational trial of ZYN002, the RECONNECT study, for the treatment of Fragile X Syndrome (“FXS”), which was designed to confirm the positive findings from the prespecified analysis of the primary outcome in the subgroup of patients with complete methylation from the Phase 2/3 CONNECT study conducted by Zynerba.

The RECONNECT study did not meet the primary endpoint of improvement in social avoidance primarily due to a higher-than-expected placebo response rate.

Additionally,

a n open-label phase 2 proof-of-concept study conducted by Zynerba showed positive signals for ZYN002 in the treatment of behavioral symptoms associated with 22q deletion syndrome, a disorder caused by a small missing piece on the long arm of the 22nd chromosome.

After an in-depth review of the data from the RECONNECT study, the ZYN002 program in FXS is being phased out and we are no longer pursuing an indication for 22q deletion syndrome .

Our industry is highly competitive and subject to rapid and significant change as research provides a deeper understanding of rare neurological disorders, including narcolepsy, and as new therapies are developed.

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The key competitive factors affecting the success of WAKIX, and any other product candidates that we develop, if approved, are likely to be efficacy, safety, convenience, price, the level of generic competition and the availability of reimbursement from government and other third-party payors.

WAKIX competes with currently FDA-approved products for the treatment of EDS or cataplexy in adult patients with narcolepsy and EDS in children six years and older with narcolepsy, all of which are controlled substances.

WAKIX competes with currently FDA-approved products for the treatment of EDS and/or cataplexy in adults and pediatric patients six years and older with narcolepsy, all of which are controlled substances.

Jazz Pharmaceuticals’ Xyrem (sodium oxybate) is an FDA-approved product for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy.

Xyrem is a Schedule III controlled substance available only through a restricted access REMS program.

Xyrem is a Schedule III controlled substance available only through a restricted access Risk Evaluation and Mitigation Strategy (“REMS”) program.

Xywav, a lower sodium formulation of Xyrem, was approved in July 2020, (became commercially available in November 2020), and is also a Schedule III controlled substance subject to the same restricted access REMS program as Xyrem.

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It is not indicated for cataplexy in patients with narcolepsy.

Additionally, Avadel Pharmaceuticals launched a once nightly formulation version of sodium oxybate in June 2023.

Additionally, Avadel Pharmaceuticals (acquired by Alkermes Plc in February 2026) launched a once nightly formulation version of sodium oxybate in June 2023.

As of January 2023, Xyrem is now available as generic sodium oxybate – one version is marketed by Hikma Pharmaceuticals through their agreement with Jazz Pharmaceuticals (launched in January 2023), and the other version is marketed by Amneal Pharmaceuticals through their agreement with Jazz Pharmaceuticals (launched in July 2023).

Additionally, in September 2025, the FDA approved Amneal Pharmaceuticals’ abbreviated new drug application (“ANDA”) for a generic sodium oxybate oral solution for cataplexy and EDS in individuals with narcolepsy.

Other potential future competitive products are currently in development, including Axsome Therapeutics’ AXS-12 (reboxetine) product candidate, Suven Life Sciences’ SUVN-G3031 H3 inverse agonist product candidate, NLS Pharmaceutics mazindol ER product candidate and orexin 2 receptor agonist product candidates from Takeda, Jazz Pharmaceuticals/Sumitomo Pharma, Centessa and Alkermes among others.

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Conversely, WAKIX is priced higher than other competitors such as Provigil (modafinil), Nuvigil, Sunosi (armodafinil) and certain generic competitors, such as methylphenidate and amphetamine, which may contribute to third-party payor preferences for those lower-priced treatment options relative to WAKIX.

There are currently no FDA approved therapies for PWS.

We are aware of several companies pursuing clinical development of therapies for PWS including, but not limited to, product candidates from Acadia Pharmaceuticals Inc., Soleno Therapeutics Inc., Rhythm Pharmaceuticals, Inc.

Currently, there is one FDA approved therapy for PWS, Vykat XR (diazoxide choline), which was approved in March 2025 and is sold by Soleno Therpeutics.

Additionally, we are aware of several companies pursuing clinical development of therapies for PWS including, but not limited to, product candidates from Aardvark Therapeutics, Inc., Rhythm Pharmaceuticals, Inc.

and Palobiofarma.

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and PepGen, Inc.

There are currently no FDA approved therapies for FXS.

We are aware of several companies pursuing clinical development of therapies for FXS including, but not limited to, product candidates from Acadia Pharmaceuticals, Inc., Mirum Pharmaceuticals, Inc., Spinogenix Inc., Allos Pharma Inc.

and Connecta Therapeutics S.L.

Additionally, there are currently no FDA approved therapies for 22q.

We are aware of several companies pursing clinical development of therapies for 22q including, but not limited to, Nobias Therapeutics, Inc.’s product candidate.

There are multiple FDA approved therapies for the treatment of DS, LGS or both DS and LGS including, but not limited to, products from GW Pharmaceuticals, Ltd.

and Lunbeck, Inc.

for the treatment of DS and LGS, Biocodex for the treatment of DS and Eisai Co., Ltd.

for the treatment of LGS.

We are also aware of several companies pursuing clinical development of therapies including, but not limited to, product candidates from Supernus Pharmaceuticals, Inc.

for the treatment of DS and LGS, SK Life Science, Inc.

for the treatment of LGS and Stoke Therapeutics, Inc.

for the treatment of DS.

There are multiple FDA approved therapies for the treatment of DS, LGS or both DS and LGS including, but not limited to, products from Jazz Pharmaceuticals for the treatment of DS and LGS, UCB for the treatment

of DS and LGS, Biocodex for the treatment of DS, Eisai Co., Ltd.

for the treatment of LGS, Janssen for the treatment of LGS, GlaxoSmithKline for the treatment of LGS, and Assertio Holdings for the treatment of LGS.

We are also aware of several companies pursuing clinical development of therapies including, but not limited to, product candidates from Stoke Therapeutics for the treatment of DS, Encoded for the treatment of DS, Lundbeck for the treatment of DEE (including DS and LGS), Bright Minds for the treatment of DEE (including DS and LGS), and Praxis Precision Medicines for the treatment of DEE (including DS and LGS).

Manufacturing, Supply and Distribution

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● Corden Pharma Chenôve SAS, a full-service contract development and manufacturing organization (“CDMO”) manufactures our API.

● Patheon UK Limited, a CDMO owned by Thermo Fisher Scientific Inc., manufactures our finished product tablets and fills them into unlabeled bottles.

● Pharma Packaging Solutions, LLC dba Tjoapack, LLC, handles our labeling and secondary packaging.

● Procos, S.p.A.

operates as an alternate drug substance manufacturing site for WAKIX API.

● Patheon UK Limited and Patheon Pharmaceuticals, Inc., CDMOs owned by Thermo Fisher Scientific Inc., manufacture our finished product tablets.

● Pharma Packaging Solutions, LLC dba Tjoapack, LLC, fills unlabeled bottles and performs labeling and secondary packaging.

● Cardinal Health, Inc.

is our third-party logistics provider.

● Inmar Rx Solutions, Inc., an advanced technology and data analytics company, specializes in reverse distribution of our product and manages our pharmaceutical returns and product recall, if needed.

We depend on a single supplier of the active pharmaceutical ingredient (“API”) for our commercial product, WAKIX, and single API suppliers for each of our potential product candidates .

is our third-party logistics provider and manages reverse distribution, pharmaceutical returns and product recall, if needed.

We depend on two suppliers of the active pharmaceutical ingredient (“API”) for our commercial product, WAKIX, and single API suppliers for each of our potential product candidates .

For the year ended December 31, 2025, three customers accounted for 100% of gross product revenue;

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License and Commercialization Agreements with Bioprojet

In July 2017, we and Bioprojet entered into the Bioprojet License Agreement (the “2017 LCA”).

In July 2017, we and Bioprojet entered into the 2017 LCA.

Bioprojet granted to us an exclusive license to commercialize, in the United States and its territories, commonwealths, and protectorates, including Puerto Rico, a product containing pitolisant currently known as WAKIX for narcolepsy, obstructive sleep apnea, idiopathic hypersomnia, Parkinson’s disease, and any other indication agreed upon by the parties which currently include PWS and DM (“the field”), as well as rights to related patent rights, know-how, trademarks, trade dress, regulatory filings and approvals (the “Bioprojet Assets”).

Bioprojet also granted us a co-exclusive (with Bioprojet) license to Bioprojet Assets to clinically develop and register the pitolisant product in the field in the United States.

Bioprojet also granted us a co-exclusive (with Bioprojet) license to Bioprojet Assets to clinically develop and

Bioprojet retains the right to manufacture the product in the United States, and to develop outside the United States and commercialize other products that contain pitolisant as an active ingredient anywhere in the world.

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In addition, certain payments will become due upon the achievement of development milestones for new indications and formulations as agreed upon by both parties.

The 2022 LCA also requires a fixed trademark royalty and a tiered royalty based on net sales upon

commercialization, payable to Bioprojet on a quarterly basis for 10 years from the first commercial sale of each new product, the expiration of all regulatory exclusivity, or the expiration of the last Bioprojet patent covering the products.

The 2022 LCA also requires a fixed trademark royalty and a tiered royalty based on net sales upon commercialization, payable to Bioprojet on a quarterly basis for 10 years from the first commercial sale of each new product, the expiration of all regulatory exclusivity, or the expiration of the last Bioprojet patent covering the products.

The $30.0 million licensing fee was recorded in research and development expenses within the consolidated statement of operations and comprehensive income (loss) for the year ended December 31, 2022.

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BP1.15205 is currently in pre-clinical development with IMPD submission anticipated in mid-2025.

Under the Sublicense, we paid Bioprojet an upfront license fee of $25.5 million, which we recognized as an IPR&D charge recorded in research and development within the consolidated statements of operations and comprehensive income for the year ended December 31, 2024, and will also be obligated to pay up to $127.5 million upon achievement of development and regulatory milestones and up to $240.0 million upon achievement of sales-based milestones, as well as royalty rates in the mid-teens on any sales of product using BP1.15205 in the Licensed Territories.

In November 2025, we achieved a clinical milestone for BP1.15205 that triggered a $4.3 million payment to Bioprojet under the Sublicense, which was paid in December 2025.

We will also be obligated to pay up to $123.2 million upon the achievement of other development and regulatory milestones and up to $240.0 million upon the achievement of certain sales-based milestones, as well as royalty rates in the mid-teens on any sales of product using BP1.15205 in the Licensed Territories.

Intellectual Property

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and foreign patents and applications relating to our technology, inventions, and improvements that are important to the development and implementation of our business.

Our WAKIX patent portfolio comprises of four U.S.

Our WAKIX patent portfolio consists of four U.S.

patents and a U.S.

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and 9,650,378), and issued patents in Australia, Brazil, Canada, China, Germany, Spain, France, United Kingdom, Israel, Italy, Japan, Korea, Mexico, and New Zealand.

The patents have claims directed to certain human MCH-1 receptor-selective

antagonists as compositions of matter, and are expected to expire in June 2031 (the ‘308 patent) and January 2029 (the ‘743 and ‘378 patents, as well as the international patents).

The third patent family comprises pending applications in the United States., Europe, Japan, China, and Hong Kong which have claims directed to therapeutic combinations or formulations of drugs comprising a melanin-concentrating hormone (“MCH-1”) receptor antagonist, and methods of treating or preventing hyperphagia, moderate to severe binge eating disorder, bulimia nervosa, among other disorders, and management of obesity using an MCH-1 receptor agonist, and also has claims to certain MCH-1 receptor antagonists as compositions of matter.

The patents have claims directed to certain human MCH-1 receptor-selective antagonists as compositions of matter, and are expected to expire in June 2031 (the ‘308 patent) and January 2029 (the ‘743 and ‘378 patents, as well as the international patents).

The third patent family comprises pending applications in the United States., Europe, Japan, China, and Hong Kong which have claims directed to therapeutic combinations or formulations of drugs comprising a melanin-concentrating hormone (“MCH-1”) receptor antagonist, and methods of treating or preventing hyperphagia, moderate to severe binge eating disorder, and bulimia nervosa, among other disorders, and management of obesity using an MCH-1 receptor agonist, and also has claims to certain MCH-1 receptor antagonists as compositions of matter.

Our EPX-100 patent family includes pending applications in the United States., Europe, Australia, Brazil, Canada, China, Hong Kong, Japan, Korea, and Eurasia.

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In addition, for patents that cover an FDA-approved drug, the Drug Price Competition and Patent Term Restoration Act of 1984 (the “Hatch-Waxman Act”) permits a patent term extension of up to five years beyond the expiration of the patent.

While the length of the patent term extension is related to the length of time the drug is under regulatory review, patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, and only one patent per approved drug may be extended under the Hatch-Waxman Act.

While the length of the patent term extension is related to the length of time the drug is under regulatory review, patent term extension cannot extend the remaining term

of a patent beyond a total of 14 years from the date of product approval, and only one patent per approved drug may be extended under the Hatch-Waxman Act.

The patent positions of companies like ours are generally uncertain and involve complex legal and factual questions.

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Moreover, because of the extensive time required for development, testing and regulatory review of a potential product, it is possible that, before any particular product candidate can be commercialized, any patent protection for such product may expire or remain in force for only a short period following commercialization, thereby reducing the commercial advantage the patent provides.

We and/or our licensor also rely on protections under trade secret laws, and seek to protect and maintain the confidentiality of proprietary information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.

We and/or our licensors also rely on protections under trade secret laws, and seek to protect and maintain the confidentiality of proprietary information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.

Our trade secrets include, for example, certain program specific synthesis, formulations, patient selection strategies and certain aspects of our research.

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Where applicable, the agreements provide that all inventions to which the individual contributed as an inventor shall be assigned to us, and as such, will become our property.

be no assurance, however, that these agreements will provide meaningful protection or adequate remedies for our trade secrets in the event of unauthorized use or disclosure of such information.

There can be no assurance, however, that these agreements will provide meaningful protection or adequate remedies for our trade secrets in the event of unauthorized use or disclosure of such information.

Further, we have in-licensed from Bioprojet the registered trademark product name “WAKIX” in the United States.

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Clinical trials must be conducted under protocols detailing the objectives of the trial, dosing procedures, subject selection and exclusion criteria and the safety and effectiveness criteria to be evaluated.

the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated.

Each protocol must be submitted to the FDA as part of the IND, and a separate submission to the existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments.

While the IND is active, progress reports summarizing the results of the clinical trials and nonclinical studies performed since the last progress report, among other information, must be submitted at least annually to the FDA, and written IND safety reports must be submitted to the FDA and investigators for serious and unexpected serious adverse events, findings from other studies suggesting a significant risk to humans exposed to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans, and any clinically important increased incidence of a serious suspected adverse reaction compared to that listed in the protocol or investigator brochure.

Furthermore, an independent IRB at each institution participating in the clinical trial must review and approve each protocol before a clinical trial commences at that institution and must also approve the information regarding the trial and the consent form that must be provided to each trial subject or his or her legal representative, monitor the study until completed and otherwise comply with IRB regulations.

Furthermore, an independent Institutional Review Board (“IRB”) at each institution participating in the clinical trial must review and approve each protocol before a clinical trial commences at that institution and must also approve the information regarding the trial and the consent form that must be provided to each trial subject or his or her legal representative, monitor the study until completed and otherwise comply with IRB regulations.

The FDA or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk.

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An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

A complete response letter usually describes the specific deficiencies in the

NDA identified by the FDA and may require additional clinical data, such as an additional clinical trial or other significant and time-consuming requirements related to clinical trials, nonclinical studies or manufacturing.

A complete response letter usually describes the specific deficiencies in the NDA identified by the FDA and may require additional clinical data, such as an additional clinical trial or other significant and time-consuming requirements related to clinical trials, nonclinical studies or manufacturing.

Even with the resubmission of the application with this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

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Specifically, investigational drugs are eligible for fast-track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition.

The sponsor of a fast-track product candidate has opportunities for more frequent interactions with the applicable FDA review team during product development and, once an NDA is submitted, the application may be eligible for priority review.

The sponsor of a fast-track product candidate has opportunities for more frequent interactions with the applicable FDA review team during product development and, once an

NDA is submitted, the application may be eligible for priority review.

With regard to a fast track product candidate, the FDA may consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA.

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Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented.

FDA regulations also require investigation and correction of any deviations from cGMP requirements and impose reporting and documentation requirements upon the sponsor and any third-party manufacturers that the sponsor may decide to use.

FDA regulations also require investigation and correction of any deviations from cGMP requirements and impose reporting and documentation requirements upon the sponsor and any third-party

manufacturers that the sponsor may decide to use.

Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain cGMP compliance.

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Such off-label uses are common across medical specialties.

Physicians may believe that such off-label uses are the best treatment for many patients in

varied circumstances.

Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances.

The FDA does not regulate the behavior of physicians in their choice of treatments.

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A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance.

During the exclusivity period, the FDA may not approve or even accept for review an abbreviated new drug application (“ANDA”) or an NDA submitted under Section 505(b)(2) (“505(b)(2) NDA”) submitted by another company for another drug based on the same active moiety, regardless of whether the drug is intended for the same indication as the original innovative drug or for another indication, where the applicant does not own or have a legal right of reference to all the data required for approval.

During the exclusivity period, the FDA may not approve or even accept for review an ANDA or an NDA submitted under Section 505(b)(2) (“505(b)(2) NDA”) submitted by another company for another drug based on the same active moiety, regardless of whether the drug is intended for the same indication as the original innovative drug or for another indication, where the applicant does not own or have a legal right of reference to all the data required for approval.

However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder.

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Orphan Drug Designation and Exclusivity

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, which is a disease or condition that (i) affects fewer than 200,000 individuals in the United States, or (ii) if it affects more than 200,000 individuals in the United States, there is no reasonable expectation that the cost of developing and making the product available in the United States for the disease or condition will be recovered from sales of the product.

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, which is a disease or condition that (i) affects fewer than 200,000 individuals in the United States, or (ii) if it affects more than 200,000 individuals in the United States and there is no reasonable expectation that the cost of developing and making the product available in the United States for the disease or condition will be recovered from sales of the product.

Orphan designation must be requested before submitting an NDA.

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Similar to the U.S.

federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the healthcare fraud statute implemented under HIPAA or specific intent to violate it in order to have committed a violation.

federal Anti-Kickback Statute, a person or entity does not need to have actual

knowledge of the healthcare fraud statute implemented under HIPAA or specific intent to violate it in order to have committed a violation.

The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services (“CMS”) information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician practitioners (physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, anesthesiologist assistants, and certified nurse midwives) and teaching hospitals, and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by physicians and their immediate family members.

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Failure to comply with these laws, where applicable, can result in the imposition of significant civil and/or criminal penalties and private litigation.

For example, California recently enacted legislation, the California Consumer Privacy Act (“CCPA”), which went into effect January 1, 2020.

For example, California recently

enacted legislation, the California Consumer Privacy Act (“CCPA”), which went into effect January 1, 2020.

The CCPA, among other things, creates new data privacy obligations for covered companies and provides new privacy rights to California residents, including the right to opt out of certain disclosures of their information.

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The relationship between the United Kingdom and the European Union in relation to certain aspects of data protection law remains unclear, and it is unclear how United Kingdom data protection laws and regulations will develop in the medium to longer term, and how data transfers to and from the United Kingdom will be regulated in the long term.

The European Commission has adopted an adequacy decision in favor of the United Kingdom, enabling data transfers from EU member states to the United

Kingdom without additional safeguards.

The European Commission has adopted an adequacy decision in favor of the United Kingdom, enabling data transfers from EU member states to the United Kingdom without additional safeguards.

However, the UK adequacy decision will automatically expire in June 2025 unless the European Commission re-assesses and renews or extends that decision.

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In the United States and certain foreign jurisdictions, there have been, and we expect there will continue to be, a number of legislative and regulatory changes to the healthcare system.

In March 2010, the ACA was signed into law, which substantially changed the way healthcare is financed by both governmental and private insurers in the United States and significantly affected the pharmaceutical industry.

The ACA contained a number of provisions, including those governing enrollment in federal healthcare programs, reimbursement adjustments and fraud and abuse changes.

Additionally, the ACA increased the minimum level of Medicaid rebates payable by manufacturers of brand name drugs;

required collection of rebates for drugs paid by Medicaid managed care organizations;

required manufacturers to participate in a coverage gap discount program, which was replaced by a new manufacturer discount program on January 1, 2025 (as discussed below), under which they were required to offer point-of-sale discounts (increased to 70 percent pursuant to the Bipartisan Budget Act of 2018, effective as of January 1, 2019) off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D;

imposed a non-deductible annual fee on pharmaceutical manufacturers or importers who sell certain “branded prescription drugs” to specified federal government programs, implemented a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted, or injected expanded the types of entities eligible for the 340B drug discount program;

expanded eligibility criteria for Medicaid programs;

created a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research;

and established a Center for

Medicare and Medicaid Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.

The ACA was signed into law in 2010, which substantially changed the way healthcare is financed by both governmental and private insurers in the United States and significantly affected the pharmaceutical industry.

Among the provisions of the ACA of importance to us and our business are an increase of the minimum level of Medicaid rebates payable by manufacturers of brand name drugs;

expansion of manufacturer Medicaid rebate liability to include drugs paid by Medicaid managed care organizations;

a non-deductible annual fee on pharmaceutical manufacturers or importers who sell certain “branded prescription drugs” to specified federal government programs;

the new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research;

and the Center for Medicare and Medicaid Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending.

Since its enactment, there have been judicial, executive and Congressional legislative challenges to certain aspects of the ACA.

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Thus, the ACA will remain in effect in its current form.

Other legislative changes have also been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers, which was temporarily suspended from May 1, 2020 through March 31, 2022 under the Coronavirus Aid, Relief and Economic Security Act (“CARES Act”), and further reduced payments to several types of Medicare providers.

In March 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminated the statutory Medicaid drug rebate cap for single source and innovator multiple source drugs, beginning January 1, 2024.

Other legislative changes have also been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers.

The American Rescue Plan Act of 2021 eliminated the statutory cap on manufacturers’ Medicaid drug rebate liability, beginning January 1, 2024.

The rebate was previously capped at 100% of a drug’s average manufacturer price.

Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted legislation designed, among other things, to bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for pharmaceutical products in an attempt to control drug costs.

Individual states in the United States have also become increasingly active in implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures and, in some cases, mechanisms to encourage importation from other countries and bulk purchasing.

The Inflation Reduction Act (the “IRA”) was enacted in 2022.

This statute marks the most significant action by Congress with respect to the pharmaceutical industry since adoption of the ACA in 2010.

Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare, with prices that can be negotiated subject to a cap;

imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023);

redesigns the Medicare Part D benefit (beginning in 2024);

and replaces the Part D coverage gap discount program with a new manufacturer discount program (beginning in 2025).

CMS has published the negotiated prices for the initial ten drugs, which became effective in 2026, and the subsequent 15 drugs, which will first be effective in 2027.

CMS has also published the next set of 15 drugs that will be subject to negotiation.

The IRA permits the Secretary of the Department of Health and Human Services (“HHS”) to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

HHS has and will continue to issue and update guidance as these programs are implemented, although the Medicare drug price negotiation program is currently subject to legal challenges.

While the impact of the IRA on the pharmaceutical industry cannot yet be fully determined, it is likely to be significant.

Under the IRA manufacturer discount program that replaced the previous coverage gap discount program as of January 1, 2025, manufacturers must give a 10 percent discount on Part D drugs in the initial coverage phase, and a 20 percent discount on Part D drugs in the so-called “catastrophic phase” (the phase after the patient incurs costs above the initial phase out-of-pocket threshold, which is $2,000 beginning in 2025).

The IRA allows the 10 and 20 percent discounts

to be phased in over time for certain drugs for “specified manufacturers.” CMS informed us that we are deemed a specified small manufacturer.

We are still evaluating the potential impact of this status on our future revenues.

The One Big Beautiful Bill Act, which was enacted in July 2025, imposes significant reductions in the funding of the Medicaid program.

Such reductions are expected to decrease the number of persons enrolled in Medicaid and reduce the services covered by Medicaid, which could adversely affect our sales of WAKIX or any other product candidate that we commercialize.

The Trump administration is pursuing a two-fold strategy to reduce drug costs in the U.S.

While it is unclear whether and how the Trump proposals will be implemented, the Trump policies are likely to have a negative impact on the pharmaceutical industry and may have a negative impact on our ability to receive adequate revenues for WAKIX.

On the one hand, President Trump has threatened to impose significant tariffs on pharmaceutical manufacturers that do not adopt pricing policies such as most favored nation pricing, which would tie the price for drugs in the U.S.

to the lowest price in a group of other countries.

In response, multiple manufacturers have reportedly entered into confidential pricing agreements with the federal government.

On the other hand, the Trump administration is pursuing traditional regulatory pathways to impose drug pricing policies, and published two proposed regulations in December 2025, referred to as Globe and Guard.

If finalized, these regulations would implement mandatory payment models under which manufacturers of eligible drugs would be required to pay rebates to the federal government on a portion of the units of their drugs that are reimbursed by Medicare, with the rebate amount based on most favored nation pricing.

Imposing a rebate in the U.S.

that is based on drug prices outside the U.S.

would mark a drastic and unprecedented shift in the U.S.

pharmaceutical market, and while the impact of the Globe and Guard proposed regulations, if finalized, cannot yet be determined, it is likely to be significant.

Even regulatory proposals or executive actions that are ultimately deemed unlawful could negatively impact the U.S.

pharmaceutical sector and our business.

Individual states in the United States have also become increasingly active in implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access, marketing cost disclosure, drug price reporting and other transparency measures.

Some states have enacted legislation creating so-called prescription drug affordability boards, which ultimately may attempt to impose price limits on certain drugs in these states, and at least one state board is imposing an upper payment limit.

States are also seeking to implement general, across the board price caps for pharmaceuticals, or are seeking to regulate drug distribution.

Some measures are designed to encourage importation from other countries and bulk purchasing.

In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine which drugs and suppliers will be included in their healthcare programs.

Furthermore, there has been increased interest by third-party payors and governmental authorities in reference pricing systems and publication of discounts and list prices.

The Inflation Reduction Act of 2022, or IRA, which was signed into law on August 16, 2022, included several provisions to reduce drug spending by the federal government and reduce out-of-pocket costs for patients on Medicare.

This legislation requires that the federal government negotiate prices for some drugs covered under Medicare Part B and Part D with the highest total spending, beginning in 2026.

It also requires manufacturers to pay rebates back to the federal government if the price of their medications for Medicare beneficiaries rises faster than inflation.

The legislation also placed a cap on out-of-pocket costs for Medicare Part D enrollees and shifted the cost of supplying these medications to manufacturers and plans.

Eligibility for the Medicare Part D Low-Income Subsidy Program was also expanded under the legislation, and it further delayed the implementation of the Trump Administration’s drug rebate rule to 2027.

While the IRA includes an exemption for orphan drugs with a single approved indication, rare disease therapies with multiple indications may become subject to Medicare price negotiations.

The IRA permits the Secretary of the Department of Health and Human Services, or HHS, to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

On August 15, 2024, HHS announced the agreed-upon prices for the first ten drugs that are subject to price negotiations, which take effect in January 2026.

HHS will select up to fifteen additional products covered under Part D for negotiation in 2025.

Each year thereafter, more Part B and Part D products will become subject to the HHS price negotiation program, although the program is currently subject to legal challenges.

For that and other reasons, it is currently unclear how the IRA will be effectuated, or the impact of the IRA on our business.

We expect that additional state and federal healthcare reform measures, particularly in light of the new presidential administration, will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our products or additional pricing pressures .

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In December 2020, we leased additional office space at this same location, which increased our footprint to approximately 35,781 square feet of office space.

In November 2025, we extended the lease for our corporate headquarters through March 31, 2031.

As of December 31, 2025, 101 of our employees are located at our corporate headquarters.

Pursuant to our Right of Use Agreement with Paragon, we also utilize office space at 330 N.

Pursuant to our right of use agreement with Paragon Biosciences, LLC (“Paragon”), we also utilize office space at 330 N.

Wabash Ave, Suite 3500, Chicago, Illinois 60611, where 7 of our employees are located.

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

What changed 10-K

Item 1. Business