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Item 1. Business

2023-03-09 compared with 2022-04-13 · 303 added, 1013 removed, 548 unchanged (71% of the section changed)

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(the Company) is a biopharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases.

Our diverse neuroscience portfolio includes approved treatments for epilepsy, migraine, hypomobility in Parkinson's Disease (PD), cervical dystonia, and chronic sialorrhea.

We are developing a broad range of novel CNS product candidates, including new potential treatments for attention-deficit hyperactivity disorder (ADHD), hypomobility in PD, epilepsy, depression, and other CNS disorders.

Our diverse neuroscience portfolio includes approved treatments for epilepsy, migraine, attention-deficit hyperactivity disorder (ADHD), hypomobility in Parkinson’s Disease (PD), cervical dystonia, chronic sialorrhea, dyskinesia in PD patients receiving levodopa-based therapy, and drug-induced extrapyramidal reactions in adult patients.

The Company is developing a broad range of novel CNS product candidates including new potential treatments for hypomobility in PD, epilepsy, depression, and other CNS disorders.

The Company was incorporated in Delaware, commenced operations in 2005, became publicly traded in 2012, and is listed on the NASDAQ Stock Exchange under the ticker symbol SUPN.

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in 2005, as Supernus Pharmaceuticals.

On February 18, 2022, we received a notice from the U.S.

Food Drug Administration (FDA) that its New Drug Application (NDA) resubmission for SPN-830 (apomorphine infusion device) for the continuous treatment of motor fluctuations ("off" episodes) in PD is considered a Standard Review, thereby assigning a timeline of 10 months for review by the FDA and establishing a Prescription Drug User Fee Act (PDUFA) target action date of October 7, 2022.

On October 10, 2021, we entered into an Agreement and Plan of Merger (Merger Agreement) by and among the Company, Adamas Pharmaceuticals, Inc.

(Adamas) and Supernus Reef, Inc., a Delaware corporation and a wholly owned subsidiary of the Company (Purchaser).

On November 24, 2021, the Purchaser was merged with and into Adamas (Merger), with Adamas continuing as the surviving corporation in the Merger as a wholly owned subsidiary of the Company (Adamas Acquisition).

At the time of the Adamas Acquisition, Adamas held and markets two established commercial products in its portfolio, GOCOVRI® and Osmolex ER®, and had royalty rights to Namzaric®.

Allergan plc markets and sells Namzaric in the United States.

Following the Adamas Acquisition, during the fourth quarter of 2021 and continuing into the first quarter of 2022, Adamas was reorganized with the interests of Adamas Pharmaceuticals, LLC, formerly Adamas Pharmaceuticals, Inc, in GOCOVRI and Osmolex ER were effectively transferred to Adamas Operations, LLC (Adamas Operations).

Adamas Operations, and Adamas Pharmaceuticals, LLC are wholly-owned subsidiaries of Adamas Holdings, LLC (collectively, the "Adamas Subsidiaries").

Adamas Holdings, LLC is a wholly-owned subsidiary of Supernus Pharmaceuticals, Inc.

During the first quarter of 2022, Supernus Pharmaceuticals, Inc.

was granted a license by Adamas Operations to market and sell GOCOVRI and Osmolex ER (such reorganization and licensing arrangement, the "Adamas Reorganization").

Each of the Adamas Subsidiaries are distinct legal entities that contract with Supernus Pharmaceuticals, Inc.

for the provision of certain corporate and other support services.

On April 2, 2021, the FDA approved Qelbree (viloxazine extended-release capsule) for the treatment of ADHD in pediatric patients 6 to 17 years of age.

In May 2021, we launched Qelbree in the U.S.

On September 2, 2021, the FDA has acknowledged receipt of the supplemental new drug application (sNDA) for Qelbree for adult patients with ADHD and assigned a PDUFA target action date of April 29, 2022.

On April 28, 2020, we entered into a Sale and Purchase Agreement with US WorldMeds Partners, LLC to acquire the CNS portfolio of USWM Enterprises, LLC (USWM Enterprises) (USWM Acquisition).

With the acquisition, completed on June 9, 2020, the Company added three established commercial products and a product candidate in late-stage development to its portfolio, through its subsidiaries.

These commercial products, APOKYN, XADAGO, and MYOBLOC, are primarily for the treatment of PD.

In the second quarter of 2021 and within one year from the Closing Date, the Company finalized its accounting for the business combination, including the purchase price allocation.

On April 21, 2020, we entered into a Development and Option Agreement (Development Agreement) with Navitor Pharmaceuticals, Inc.

(Navitor Inc.) and also acquired an ownership position in Navitor Inc.

Under the terms of the Development Agreement, the Company and Navitor Inc.

will jointly conduct a Phase II clinical program for NV-5138 (SPN-820) in treatment resistant depression (TRD).

In March 2021, Navitor Inc.

underwent a legal restructuring whereby Navitor Inc.

became a wholly owned subsidiary of a newly formed limited liability company, Navitor Pharmaceuticals, LLC (Navitor LLC) (Navitor Restructuring) and our ownership position in Navitor Inc.

was exchanged for an equivalent ownership position in Navitor LLC.

In December 2021, we received a $12.9 million cash distribution pursuant to our ownership position in Navitor LLC following its sale of its subsidiary.

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Adamas Acquisition and Reorganization

On October 10, 2021, the Company entered into an Agreement and Plan of Merger by and among the Company, Adamas Pharmaceuticals, Inc.

(Adamas) and Supernus Reef, Inc., a Delaware corporation and a wholly-owned subsidiary of the Company (Purchaser) (Adamas Agreement).

On November 24, 2021 (the Closing Date), the Company completed its purchase of all of the outstanding equity of Adamas, pursuant to the Adamas Agreement dated October 10, 2021, and the Purchaser was merged with and into Adamas (the Merger), with Adamas continuing as the surviving corporation in the Merger as a wholly-owned subsidiary of the Company (Adamas Acquisition).

On the Closing Date, Adamas owned two marketed products:

GOCOVRI (amantadine) extended-release capsules, the first and only FDA approved medicine indicated for the treatment of both "off" episodes and dyskinesia in patients with PD receiving levodopa-based therapy and as an adjunctive treatment to levodopa/carbidopa in patients with PD experiencing "off" episodes;

and Osmolex ER (amantadine) extended-release tablets, approved for the treatment of PD and drug-induced extrapyramidal reactions in adult patients.

Adamas also owns the right to receive royalties from Allergan plc for sales of Namzaric (memantine hydrochloride extended-release and donepezil hydrochloride) in the United States.

In the first quarter of 2022 and subsequent to the Adamas Acquisition, the Company completed a reorganization of the Adamas legal entities in an effort to obtain operational, legal and other benefits that also resulted in certain state tax efficiencies.

The reorganization had no effect on the consolidated financial statements other than certain state tax efficiencies.

Refer to Note 12, Income Tax (Benefit) Expense in Part II, Item 8 — Financial Statements of this report.

Our mission is to improve the lives of patients suffering from CNS diseases.

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• Drive growth and profitability.

Using dedicated sales and marketing resources in the U.S., we will continue to drive the revenue growth of our market products.

• Advance our current pipeline toward commercialization.

We have a portfolio of early to late-stage product candidates.

We continue to advance our late-stage product candidate, Qelbree (viloxazine hydrochloride) for treatment of ADHD in adults and SPN-830 (apomorphine infusion device) for treatment of hypomobility in PD, to regulatory approval and commercialization.

Using dedicated sales and marketing resources in the U.S., we will continue to drive the revenue growth of our marketed products.

• Advance product candidates toward commercialization.

Several product candidates in our pipeline are in early-to-late stage clinical testing, and moving toward being commercially available to patients.

• Continue to grow our pipeline.

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Our commercial products, including those sold by or through our subsidiaries, include:

Qelbree (viloxazine extended-release capsules) is a novel non-stimulant product indicated for the treatment of ADHD in adults and pediatric patients 6 years and older.

On April 2, 2021, the FDA approved Qelbree for the treatment of ADHD in pediatric patients 6 to 17 years of age.

In May 2021, the Company launched Qelbree for pediatric patients in the U.S.

On April 29, 2022, the FDA approved Qelbree for treatment of ADHD in adult patients.

The Company launched Qelbree for adult patients in May 2022.

Trokendi XR ®

Trokendi XR is indicated for (1) Epilepsy:

initial monotherapy for the treatment of partial-onset and primary generalized tonic-clonic (PGTC) seizure in patients 6 years of age and older (1.1);

adjunctive therapy for the treatment of partial-onset, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut Syndrome in patients 6 years of age and older (1.2);

and for (2) preventive treatment of migraine in patients 12 years of age and older.

Trokendi XR is the first once-daily extended release topiramate product indicated for the treatment of epilepsy and the prophylaxis of migraine headaches in adults and adolescents in the U.S.

Trokendi XR is indicated for:

initial monotherapy in patients 6 years of age and older with partial onset or primary generalized tonic-clonic (PGTC) seizures;

as add-on therapy in patients 6 years of age and older with partial onset or PGTC seizures or with seizures associated with Lennox-Gastaut Syndrome;

and for prophylaxis of migraine headache in adults and adolescents 12 years of age and older.

Trokendi XR's once-daily dosing is designed to improve patient adherence over the current immediate release products, which must be taken multiple times per day.

We believe a once-daily dosing regimen improves adherence, making it more probable that patients take their medication and maintain sufficient levels of medication in their bloodstreams.

Trokendi XR's unique smooth pharmacokinetic profile results in lower peak plasma concentrations, higher trough plasma concentrations, and slower plasma uptake rates.

This results in smoother and more consistent plasma concentrations than immediate release topiramate formulations.

We believe that such a profile mitigates blood level fluctuations that are frequently associated with many side effects, thereby reducing the likelihood of breakthrough seizures or migraine headaches that patients can suffer when taking immediate release products.

Side effects associated with immediate release products may lead patients to skip doses, which could place patients at higher risk for breakthrough seizures or migraine headaches.

Pursuant to the U.S.

Food and Drug Administration's (FDA) approval of Trokendi XR, the FDA granted a deferral for submission of post-marketing pediatric studies in the following categories:

(1) adjunctive therapy in partial onset seizures (POS) for children one month to less than six years of age;

(2) initial monotherapy in POS and PGTC for children two years to less than ten years of age;

and (3) adjunctive therapy in PGTC and adjunctive therapy in Lennox-Gastaut Syndrome for patients aged two years to less than six years of age.

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The Company entered into settlement agreements with third parties permitting the sale of a generic version of Trokendi XR on or after January 1, 2023.

For more information, refer to Part I, Item I—Business — Intellectual Property and Exclusivity in this annual Report on Form 10-K.

Oxtellar XR ®

Oxtellar XR is indicated for treatment of partial-onset seizure in adults and children 6 years of age and older.

Oxtellar XR is the first once-daily extended release oxcarbazepine product indicated for the treatment of epilepsy in the U.S.

In 2013, we launched Oxtellar XR for adjunctive therapy in the treatment of partial seizures in adults and children 6 to 17 years of age.

In 2013, we launched Oxtellar XR for adjunctive therapy in the treatment of partial-onset seizures in adults and children 6 to 17 years of age.

In January 2019, we launched Oxtellar XR for monotherapy treatment of partial onset epilepsy seizures in adults and children 6 to 17 years of age.

Oxtellar XR is indicated as therapy of POS in adults and children 6 years to 17 years of age.

With its novel pharmacokinetic profile showing lower peak plasma concentrations, a slower rate of plasma input, and smoother and more consistent blood levels as compared to immediate release products, we believe Oxtellar XR improves the tolerability of oxcarbazepine and thereby reduces side effects.

In addition, Oxtellar XR once-per-day dosing is designed to improve patient adherence compared to the current immediate release products that must be taken multiple times per day.

Pursuant to the FDA's approval of Oxtellar XR, we committed to conducting four pediatric post-marketing studies;

however, the FDA granted a waiver for the pediatric study requirements for ages from birth to one month, and a deferral for submission of post-marketing assessments for children one month to six years of age.

Qelbree (viloxazine extended-release capsules) is a selective norepinephrine reuptake inhibitor indicated for the treatment of ADHD in pediatric patients 6 to 17 years of age.

The FDA approved Qelbree in April 2021 for the treatment of ADHD in pediatric patients of 6 to 17 years of age, and in May 2021, we launched Qelbree in the U.S.

Given its new chemical entity (NCE) status in the U.S., Qelbree has been granted market exclusivity through April 2026.

We received approval for Qelbree from the FDA based on certain post-marketing commitments, including the requirement to conduct a clinical efficacy and six month open label safety extension study for ADHD in pediatric patients 4 to 5 years of age, a lactation study and a descriptive study related to the use of Qelbree during pregnancy, and to assess the risks of adverse events and potential complications.

We will conduct post-marketing commitment studies, including a new study of

Qelbree in preschool aged children 4 to 5 years of age with ADHD.

The completion of these studies responds to a written request from the FDA, which we expect would result in the FDA granting an additional 6 months of market exclusivity.

APOKYN (apomorphine hydrochloride injection) is a product indicated for the acute, intermittent treatment of hypomobility or "off" episodes ("end-of-dose wearing off" and unpredictable "on-off" episodes) in patients with advanced PD.

APOKYN's adjustable dose subcutaneous injection pen is designed to quickly and reliably reverse the effects of oral levodopa wearing off in patients with inadequately controlled PD.

Patients taking APOKYN saw 95% of "off" episodes reversed, with improvement beginning as quickly as 10 minutes post-dosing in clinical studies.

With the alternative of immobility and limited function, we believe the rapid and reliable reduction of "off" episode symptoms is of utmost importance to patients.

XADAGO (safinamide) is a once-daily product indicated as adjunctive treatment to levodopa/carbidopa in patients with PD who are experiencing "off" episodes.

XADAGO is a monoamine oxidase B (MAO-B) inhibitor that works by blocking the catabolism of dopamine, which is believed to result in an increase in dopamine levels, and therefore a subsequent increase in dopaminergic activity in the brain.

In March 2017, XADAGO received FDA approval.

In the XADAGO clinical trials, patients experienced more beneficial "on" time, a time when Parkinson's symptoms are reduced, without troublesome uncontrolled involuntary movement (dyskinesia), compared to those receiving a placebo.

The increase in "on" time was accompanied by a reduction in "off" time and better scores on a measure of motor function assessed during "on" time than before treatment.

MYOBLOC (rimabotulinumtoxinB) is a product indicated for the treatment of cervical dystonia and sialorrhea in adults, and it is the only Type B toxin available on the market.

Based on clinical studies, MYOBLOC injections offer patients struggling with painful cervical dystonia symptoms relief as early as two weeks after injection, with the duration of effect between 12-16 weeks.

In sialorrhea, patients generally experienced symptom relief for up to three months post-dosing in well-controlled studies.

In well controlled studies, injections of MYOBLOC have been shown to reduce the unstimulated salivary flow rate (USFR) by 0.3g/minute compared to placebo.

MYOBLOC must be administered by a physician.

MYOBLOC was first approved by the FDA in 2000 for the treatment of adults with cervical dystonia.

In August 2019, the FDA approved a supplemental Biologics License Application (sBLA) for MYOBLOC for the treatment of chronic sialorrhea in adults.

Pursuant to the FDA's approval of MYOBLOC for the treatment of chronic sialorrhea in adults, we will be conducting a clinical program under a Special Protocol Assessment from the FDA, which will address post-marketing commitments and potentially provide expanded indications for MYOBLOC.

We marketed rimabotulinumtoxinB in select European countries under the trade name NeuroBloc.

In April 2021, we notified the European Medicines Agency that we will cease the marketing of rimabotulinumtoxinB .

In addition, our collaboration partner Eisai has been marketing rimabotulinumtoxinB in Japan since 2013 under the trade name NerBloc.

GOCOVRI (amantadine) extended release capsules is the first and only FDA-approved medicine indicated for the treatment of dyskinesia in patients with PD receiving levodopa-based therapy, with or without concomitant dopaminergic medications, and as an adjunctive treatment to levodopa/carbidopa in patients with PD experiencing "off" episodes.

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GOCOVRI has been granted orphan drug exclusivity until August 24, 2024 for the treatment of dyskinesia in patients with PD receiving levodopa-based therapy with or without concomitant dopaminergic medications.

APOKYN's adjustable dose subcutaneous injection pen is designed to quickly and reliably reverse the effects of oral levodopa wearing off in patients with inadequately controlled PD.

XADAGO (safinamide) is a once-daily product indicated as adjunctive treatment to levodopa/carbidopa in patients with PD who are experiencing "off" episodes.

XADAGO was approved by the FDA in March 2017.

Osmolex ER (amantadine) extended release tablets is for the treatment of PD and drug-induced extrapyramidal reactions in adult patients.

Osmolex ER was approved by the FDA in February 2018.

MYOBLOC (rimabotulinumtoxinB) is a product indicated for the treatment of cervical dystonia to reduce the severity of abnormal head position and neck pain associated with cervical dystonia in adults and treatment sialorrhea in adults.

MYOBLOC is the only Type B toxin available on the market.

MYOBLOC injections must be administered by a physician.

MYOBLOC was approved by the FDA in December 2000 for the treatment of adults with cervical dystonia.

In August 2019, the FDA approved a supplemental Biologics License Application (sBLA) for MYOBLOC for the treatment of chronic sialorrhea in adults.

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Research and Development

We are developing a pipeline of novel CNS product candidates for the treatment of various CNS conditions.

The table below summarizes our product candidates in clinical development.

We are committed to the development of innovative product candidates in neurology and psychiatry, including the following:

Product Candidate Indication Development NDA

Qelbree (SPN-812) Adult ADHD Under Review (1)

SPN-830 Continuous prevention of "off" episodes in PD patients

Under Review (2)

SPN-820 Depression Phase II

SPN-817 Severe Epilepsy Phase I

SPN-443 CNS Preclinical

SPN-446 CNS Preclinical

(1) PDUFA target action date in April 2022.

(2) PDUFA target action date in October 2022.

SPN-830 Continuous treatment of motor fluctuations ("off" episodes) in PD patients

Complete Response Letter (CRL) received from FDA in October 2022

SPN-820 Treatment-resistant depression Phase II

SPN-817 Focal seizures Phase I

We also engage in a variety of additional research and development effort including developing a pipeline of novel CNS product candidates for the treatment of various CNS conditions.

We have devoted and continue to devote significant resources to research and development activities.

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and expanding product indications for approved products and intellectual property portfolio.

Qelbree (viloxazine extended-release capsules)

In September 2021, the FDA acknowledged it received the sNDA for Qelbree for the treatment of ADHD in adult patients with a PDUFA target action date of April 29, 2022.

Our expectations regarding our research and development programs are subject to the risks described under Item 1A—Risk Factors—Risks Related to Our Industry and Business , which includes the following risks among others — (1) The Company's financial condition and results of operations for fiscal year 2023 and beyond may be materially and adversely affected by the ongoing COVID-19 pandemic;

and (2) Delays and failures in the completion of clinical development of our product candidates would increase our costs, delay, or limit our ability to generate revenues.

SPN-830 (apomorphine infusion device)

SPN-830 is a late-stage drug/device combination product candidate for the treatment of continuous prevention of "off" episodes in PD patients.

SPN-830 is a late-stage drug/device combination product candidate for the continuous treatment of motor fluctuations ("off" episodes) in PD patients that are not adequately controlled with oral levodopa and one or more adjunct PD medications.

If approved, it would be the only continuous infusion of apomorphine available in the U.S.

and an important step for PD patients that would have otherwise been candidates for potentially invasive surgical procedures, such as deep brain stimulation.

Continuous infusion may also limit some of the side effects of a subcutaneous injection of apomorphine.

In September 2020, we submitted an NDA to the FDA for SPN-830 for the continuous treatment of motor fluctuations ("on-off" episodes) in PD patients.

In November 2020, we received a Refusal to File (RTF) letter from the FDA that stated the NDA was not sufficiently complete to permit a substantive review.

Continuous slow infusion may also limit some of the side effects of a bolus injection of apomorphine.

In December 2021, we resubmitted the NDA to the FDA.

In February 2022, we received a notice from the FDA that the resubmission of the NDA for SPN-830 is considered as a Standard Review, thereby was assigned a timeline for review of 10 months by the FDA.

The PDUFA target action date is October 7, 2022.

The Company is preparing for the commercial launch of SPN-830 in the first quarter of 2023 assuming timely approval by the FDA.

In February 2022, we received a notice from the FDA that the resubmission of the NDA for SPN-830 was considered as a Standard Review and was assigned a PDUFA target action date in early October 2022.

In October 2022, the FDA issued a Complete Response Letter (CRL) regarding the NDA for SPN-830.

The CRL requires additional information and analysis related to the infusion device and drug product across several areas of the NDA including, but not limited to, labeling, product quality and manufacturing, device performance and risk analysis.

In addition, the FDA mentions that approval of the NDA requires inspections that could not be completed in a timely manner due to COVID-19 travel restrictions.

The CRL does not request additional efficacy and safety clinical studies.

The FDA has made an initial determination that the amendment to the Company’s application in response to the CRL will be subject to a Class 2, or six-month, review timeline.

In February 2023, the FDA granted the Company a Type C meeting request to discuss the CRL with the meeting scheduled in April 2023.

SPN-820 (NV-5138)

SPN-820 is a first-in-class, orally active small molecule that activates brain mTORC1 (mechanistic target of rapamycin complex 1), a gatekeeper of cellular metabolism and renewal.

SPN-820 binds to and modulates sestrin, which senses amino acid availability in the brain, a potent natural activator of mTORC1.

Complex 1 of the mechanistic target of rapamycin (mTORC1) activity governs the pace and ability of the cell to synthesize protein and other cellular components.

This complex may be suppressed in people suffering from depression.

In other disease states such as severe depression, inadequate mTORC1 activity contributes to disease pathology by limiting energy utilization and protein synthesis, leading to impaired function.

Multiple preclinical studies have shown that mTORC1 activation is required for the efficacy of many rapid-acting antidepressant compounds, including but not limited to modulators of the N-methyl-D-aspartic-acid (NMDA)-mediated signaling pathway like ketamine.

A Phase I trial demonstrated early proof of concept in which a single dose of SPN-820 showed a rapid and sustained improvement in core symptoms, with favorable safety and tolerability in patients with treatment resistant depression.

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the novel MOA in depression may improve symptoms of depression in patients who have failed other agents.

An Investigational New Drug (IND) application was submitted to the FDA in September 2021.

We initiated a Phase II multi-center, randomized double-blind placebo-controlled parallel design study of SPN-820 in adults with treatment resistant depression.

The study will examine the efficacy and safety of SPN-820 over a course of five weeks of treatment in approximately 270 patients.

The primary outcome measure is the change from baseline to end of treatment period on the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score, a standard depression rating scale.

SPN-817 (huperzine A)

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Given the potency of SPN-817 (huperzine A), a novel extended release oral dosage form is critical to the success of this program because initial studies with the immediate release formulations of non-synthetic SPN-817 (huperzine A) have shown serious dose-limiting, side effects.

A randomized Phase II clinical study for the treatment of focal seizures in adult patients is expected to start in the second half of 2022.

SPN-820 (NV-5138)

SPN-820 is a first-in-class, orally active small molecule that directly activates brain mTORC1 (mechanistic target of rapamycin complex 1), a gatekeeper of cellular metabolism and renewal.

SPN-820 binds to and modulates sestrin, which senses amino acid availability in the brain, a potent natural activator of mTORC1.

This complex may be suppressed in people suffering from depression.

We believe the novel MOA in depression may improve symptoms of depression in patients who have failed other agents.

Complex 1 of the mechanistic target of rapamycin (mTORC1) activity governs the pace and ability of the cell to synthesize protein and other cellular components.

Increased mTORC1 activity contributes to a broad array of aging diseases by increasing protein misfolding and driving cellular stress, inflammation, and fibrosis.

In other disease states such as severe depression, inadequate mTORC1 activity contributes to disease pathology by limiting energy utilization and protein synthesis, leading to impaired function.

An Investigational New Drug (IND) application was submitted to the FDA in September 2021.

We initiated a Phase II multicenter, randomized double-blind placebo-controlled parallel design study of SPN-820 in adults with treatment resistant depression.

The study will examine the efficacy and safety of SPN-820 over a course of five weeks of treatment in approximately 400 patients.

The primary outcome measure is the change from baseline to end of treatment period on the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score, a standard depression rating scale.

SPN-443 and SPN-446 - Two novel CNS drug candidates nominated for development

Our internal research and development discovery program generated several new chemical entities including SPN-443 and SPN-446 that were nominated for development across various CNS indications.

Market Overview

Epilepsy is a complex neurological disorder characterized by the spontaneous recurrence of unprovoked seizures, which are sudden surges of electrical activity in the brain that impair a person's mental and/or physical abilities.

The Company has commenced an open-label Phase II clinical study of SPN-817 in patients with treatment-resistant seizures.

Sales and Marketing

We market our products through our own sales forces in the U.S.

and seek strategic collaborations with other pharmaceutical companies to commercialize our products outside of the U.S.

We have a commercial sales and marketing organization in the U.S.

to support sales of our commercial products.

We believe our current sales forces are effectively targeting healthcare providers to support and grow our current commercial products.

As a result of the acquisitions in 2021 and 2020, we established our commercial capabilities in the Parkinson's area with a focus on serving movement disorder specialists and other specialized health care providers in the U.S.

With the launches of Qelbree for both pediatric and adult patients, we expanded our sales efforts to market the commercial product to the relevant physician audience of psychiatrists, pediatricians, primary care physicians and allied health professionals.

Our sales representatives who previously supported Trokendi XR and Oxtellar XR now devote their full efforts to the launch of Qelbree.

The majority of our product sales are to pharmaceutical wholesalers, specialty pharmacies, and distributors who, in turn, sell our products to pharmacies, hospitals, and other customers, including federal and state entities.

The majority of sales of Oxtellar XR, Trokendi XR, Qelbree, and XADAGO are made to wholesalers and distributors.

In addition, MYOBLOC is available for direct purchase by physicians and hospitals.

The majority of sales of APOKYN and GOCOVRI are made to specialty pharmacies.

Each of our three major customers, AmerisourceBergen Drug Corporation, Cardinal Health, Inc., and McKesson Corporation, individually accounted for more than 25% of our total product revenue in 2022 and collectively accounted for more than 80% of our total product revenue in 2022.

Market and Competition

W e are engaged in segments of the pharmaceutical industry that are highly competitive and rapidly changing.

Many large pharmaceutical and biotechnology companies, academic institutions, governmental agencies, and other public and private research organizations are commercializing or pursuing the development of products for the same molecule, compound, or diseases that we are currently pursuing or may target in the future.

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ADHD is a CNS disorder characterized by developmentally inappropriate levels of inattention, hyperactivity, and impul sivity.

ADHD affects an estimated 6% to 9% of all school-age children, and an estimated 3% to 5% of adults in the U.S.

An estimated 50% of children with ADHD continue to meet the criteria for ADHD into adolescence.

Diagnosis of ADHD requires a comprehensive clinical evaluation based on identifying patients who exhibit the core symptoms of inattention, hyperactivity, and impulsivity.

Although many patients may be inattentive, hyperactive, or impulsive, the level of severity and degree of functional impairment, and considerations as to what may be behind the underlying symptoms determine which patients meet the diagnosis and therefore should be treated for ADHD.

Qelbree is a novel nonstimulant taken once-daily for full-day exposure.

Efficacy and symptom improvement was observed early in treatment in clinical studies.

Also, it has a proven safety and tolerability profile, with no evidence of abuse potential in clinical studies.

Qelbree is the first nonstimulant treatment for ADHD approved by the FDA in over a decade.

Competition in the U.S.

ADHD market has increased with the commercial launch of several branded products in recent years, as well as the launch of generic versions of branded drugs, such as Adderall XR, Intuniv, Kapvay and Strattera.

Treatment options for ADHD in the U.S.

market can be broadly classified as either stimulant or as non-stimulant products.

Epilepsy is a c omplex neurological disorder characterized by the spontaneous recurrence of unprovoked seizures, which are sudden surges of electrical activity in the brain that impair a person's mental and/or physical abilities.

Adherence with drug treatment regimens is critically important to achieving effective control for patients with epilepsy.

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The release profiles of extended release products can produce more consistent and steadier plasma concentrations as compared to immediate release products, potentially resulting in fewer side effects, better tolerability, fewer emergency room visits, improved efficacy, and fewer breakthrough seizures.

In addition, Trokendi XR's and Oxtellar XR's once-daily dosing is designed to improve patient adherence over the current immediate release products, which must be taken multiple times per day.

We believe a once-daily dosing regimen improves adherence, making it more probable that patients take their medication and maintain sufficient levels of medication in their bloodstreams.

Extended release products may help patients improve adherence and, consequently, help patients enjoy a better quality of life.

Trokendi XR competes with all immediate release and extended release topiramate products, including Topamax, Qudexy XR, and their related generic products.

Oxtellar XR competes with all immediate release oxcarbazepine products, including Trileptal and its related generic products.

Both Oxtellar XR and Trokendi XR compete with other anti-epileptic products, both branded and generic.

Many medications are used to treat epilepsy, including topiramate, oxcarbazepine, acetazolamide, brivaracetam, carbamazepine, clobazam, lacosamide, phenytoin, valproic acid, lamotrigine, gabapentin, levetiracetam phenobarbital, and zonisamide.

In addition, when considering treatment regimens for patients with epilepsy, neurologists and epileptologists take into consideration the MOA of the different AEDs that are available.

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As in epilepsy, we believe extended release products, particularly Trokendi XR, may offer important advantages for the treatment of migraines.

Extended release products can produce more consistent and steadier plasma concentrations as compared to immediate release products, potentially resulting in fewer side effects, better tolerability, fewer emergency room visits, and improved efficacy.

Extended release products may help patients improve adherence, have fewer breakthrough migraines, and consequently, help patients enjoy a better quality of life.

Trokendi XR also competes with other products used for the prevention of migraine headaches.

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notably, this includes anti-CGRPs (calcitonin gene related peptide), which is a class of products first introduced in 2018;

beta-blockers;

valproic acid;

and amitriptyline.

Parkinson's Disease

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As the disease progresses, some patients may lose the ability to independently perform the tasks of daily living.

The most commonly prescribed medicine for PD is levodopa.

PD patients are frequently prescribed levodopa to help replace dopamine, which is reduced in the brain.

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Patients in an "off" state, including those whose last dose of oral levodopa has worn off and whose next oral dose has not yet begun to take effect, can suffer from reduced coordination or mobility for several hours per day.

Carbidopa may be used along with levodopa to improve its efficacy and reduce the amount of levodopa needed to control PD symptoms.

There are a number of alternative adjunctive treatment options (FDA-approved and in clinical development) for Parkinson's patients, including various levodopa preparations, dopamine agonists, MAO-B inhibitors, and others.

APOKYN is given as needed as an adjunct to levodopa/carbidopa therapy in PD patients who experience "off" episodes.

In well-controlled clinical studies, APOKYN injections were effective in treating "off" periods, as measured by the motor function subset of the Unified Parkinson's Disease Rating Scale (UPDRS).

For patients for whom oral levodopa will not sufficiently control "off" periods, the Company has commercialized APOKYN, delivered via an injection pen.

Patients taking APOKYN saw 95% of "off" episodes reversed, with improvement beginning as quickly as 10 minutes post-dosing in clinical studies.

With the alternative of immobility and limited function, we believe the rapid and reliable reduction of "off" episode symptoms is of utmost importance to patients.

APOKYN competes with all apomorphine hydrochloride products, including KYNMOBI.

It also competes with other pro re nata (PRN) therapies such as Inbrija, and other adjunctive therapies, including NOURIANZ.

APOKYN also competes with other products for the treatment of PD, both branded and generic, including levodopa products.

For patients who experience significant "off" time each day, the Company has developed a product candidate as a continuous infusion device (SPN-830) to deliver apomorphine subcutaneously.

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For patients not ready to try parenteral therapy, oral MAO-B inhibitors, such as XADAGO, may provide a decrease in "off" time of up to one hour per day when combined with appropriate levodopa therapy.

GOCOVRI (amantadine) extended-release capsules is the first and only FDA-approved medicine indicated for the treatment of dyskinesia in patients with PD receiving levodopa-based therapy, with or without concomitant dopaminergic medications.

The increase in "on" time was accompanied by a reduction in "off" time and better scores on a measure of motor function assessed during "on" time than before treatment.

XADAGO competes with other MAO-B inhibitors used to treat "off" episodes in PD, including rasagiline (AZILECT) and selegiline (Zelapar and EMSAM).

XADAGO also competes with other products for the treatment of PD, both branded and generic, including levodopa products.

It is also the only medicine clinically proven to reduce both dyskinesia and “off” periods.

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Additionally, in the clinical trials, the adjunctive use of GOCOVRI did not require changes to dopaminergic therapies.

In well-controlled clinical studies, GOCOVRI demonstrated a durable reduction in dyskinesia and “off” time in people with PD.

In addition, the open label safety study of GOCOVRI, EASE LID 2, demonstrated a sustained improvement in levodopa-induced dyskinesia (LID) among patients using GOCOVRI.

Results showed the treatment effect of GOCOVRI on motor complications (dyskinesia and "off") was maintained for at least two years, providing long-term durability and safety data

This effect was seen in all patients in the study, including those who were switched from amantadine immediate release treatment to GOCOVRI and patients who had received deep brain stimulation treatment.

Data from the open label study were accepted for publication in the Journal of Parkinson's Disease and published online in January 2020 .

Osmolex ER is an extended release tablet formulation that contains both immediate-release and extended-release amantadine, that is dosed once daily in the morning.

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Peak serum drug concentration conveniently occurs in the middle portion of a patient’s day when the drug is administered in the morning.

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According to their prescribing information, neither GOCOVRI nor Osmolex ER are interchangeable with other amantadine immediate- or extended-release products for their respective approved indications.

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In well-controlled studies, botulinum toxins like MYOBLOC have been shown to improve symptoms as measured on the Toronto Western Spasmodic Torticollis Rating Scale, including pain.

MYOBLOC is the only available botulinum toxin B, whereas other available toxins are type A.

MYOBLOC competes with type A toxins such as Botox, Dysport, and Xeomin.

MYOBLOC also competes with oral agents used to treat cervical dystonia, including generic baclofen, anticholinergics, benzodiazepines, and tetrabenazine.

Sialorrhea can occur in conjunction with several neurologic disorders, such as amyotrophic lateral sclerosis (ALS), cerebral palsy (CP), PD, or as a side effect of some medications.

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In addition to being embarrassing, complications of sialorrhea include aspiration, infection, skin breakdown, and bad odor.

ADHD is a CNS disorder characterized by developmentally inappropriate levels of inattention, hyperactivity, and impulsivity.

ADHD affects an estimated 6% to 9% of all school-age children, and an estimated 3% to 5% of adults in the U.S.

An estimated 50% of children with ADHD continue to meet the criteria for ADHD into adolescence.

Diagnosis of ADHD requires a comprehensive clinical evaluation based on identifying patients who exhibit the core symptoms of inattention, hyperactivity, and impulsivity.

We are engaged in segments of the pharmaceutical industry that are highly competitive and rapidly changing.

Migraine and Epilepsy Competition

Trokendi XR competes with all immediate release and extended release topiramate products, including Topamax, Qudexy XR, and their related generic products.

For example, in February 2021, Glenmark Pharmaceuticals Limited (Glenmark) received final approval by the FDA for topiramate extended release capsules, the generic version of Qudexy XR capsules of Upsher-Smith Laboratories.

Trokendi XR also competes with other products used for the prevention of migraine headaches.

Most notably, this includes anti-CGRPs (calcitonin gene related peptide), which is a new class of products first introduced in 2018;

beta-blockers;

valproic acid;

and amitriptyline.

Oxtellar XR competes with all immediate release oxcarbazepine products, including Trileptal and its related generic products.

Both Oxtellar XR and Trokendi XR compete with other anti-epileptic products, both branded and generic.

Parkinson's Disease Competition

The most commonly prescribed medicine for PD is levodopa (L-dopa).

Carbidopa may be used along with levodopa to improve its efficacy and reduce the amount of levodopa needed to control PD symptoms.

APOKYN is given as needed as an adjunct to levodopa/carbidopa therapy in PD patients who experience "off" episodes.

It competes with all apomorphine hydrochloride products, including KYNMOBI.

It also competes with other PRN therapies such as Inbrija, and other adjunctive therapies, including NOURIANZ.

In February 2022, the FDA approved the first generic of Apokyn (apomorphine hydrochloride injection) to treat hypomobility "off" episodes ("end-of-dose wearing off" and unpredictable "on/off" episodes) associated with advanced Parkinson's disease.

This approval is for an application of the drug cartridges only, which are compatible for use with the APOKYN pen, the brand-name pen injector.

Patients treated with generic apomorphine hydrochloride will need to separately obtain the APOKYN pen.

Refer to Part I, Item 1A—Risk Factors – If the FDA or other applicable regulatory authorities approve generic products that compete with any of our products or product candidates, the sales of our products or the commercial success of our product candidates would be adversely affected.

Also refer to risk factor - Any impairment in the value of our intangible assets, including goodwill, would negatively affect our operating results and total capitalization.

XADAGO competes with other MAO-B inhibitors used to treat "off" episodes in PD, including rasagiline (AZILECT) and selegiline (Zelapar and EMSAM).

APOKYN and XADAGO also compete with other products for the treatment of PD, both branded and generic, including levodopa products.

GOCOVRI is the first and only FDA-approved medicine for the treatment of dyskinesia in patients with PD receiving levodopa-based therapy, with or without concomitant dopaminergic medications, and as an adjunctive treatment to levodopa/carbidopa in patients with PD experiencing "off" episodes.

GOCOVRI is marketed and sold by our subsidiary, Adamas Operations.

Adamas Operations faces competition from various branded and generic drugs approved for the treatment of PD that physicians either have historically used or may use in an attempt to manage dyskinesia.

Competition may arise from all versions of levodopa including, SINEMET, PARCOPA, RYTARY, DUOPA, INBRIJA;

dopamine agonists, including REQUIP XL, MIRAPEX and MIRAPEX ER, NEUPRO Patch, KYNMOBI;

MAO-B inhibitors including, selegiline, AZILECT;

adenosine receptor antagonist NOURIANZ;

COMT inhibitors (ONGENTYS, COMTAN, TASMAR);

and other versions of amantadine such as Symmetrel - amantadine immediate release.

GOCOVRI will also face competition from investigational drugs in late stage development for the treatment of PD, if approved, and from drugs currently in development for dyskinesia in PD or for PD, from a number of pharmaceutical companies, some of which have significantly greater resources than us.

Osmolex (amantadine) extended-release tablets is FDA-approved for the treatment of PD and drug-induced extrapyramidal reactions in adult patients.

According to the products' Prescribing Information, neither GOCOVRI nor OSMOLEX ER are interchangeable with other amantadine immediate-release or extended-release products for their respective approved indications.

Osmolex ER tablet contains an outer layer that immediately releases the medication upon the patient taking the tablet and an inner core that slowly releases the medication over long periods of time.

This allows Osmolex ER to be taken just once a day, easing complicated medication routines.

Sialorrhea and Cervical Dystonia Competition

MYOBLOC is the only available botulinum toxin B, whereas other available toxins are type A.

MYOBLOC competes with type A toxins such as Botox, Dysport, and Xeomin.

MYOBLOC also competes with oral agents used to treat cervical dystonia, including generic baclofen, anticholinergics, benzodiazepines, and tetrabenazine.

MYOBLOC competes with Xeomin (incobotulinumtoxinA) for the treatment of sialorrhea in adults.

Other pharmacologic treatments used to treat sialorrhea include generic glycopyrrolate tablets as well as behavior modification.

ADHD Competition

Competition in the U.S.

Treatment options for ADHD in the U.S.

market can be broadly classified as either stimulant or as non-stimulant products.

Takeda, Inc, one of the leaders in the U.S.

ADHD market, has four marketed products:

Vyvanse, a stimulant drug product launched in 2007;

Intuniv, a non-stimulant product launched in November 2009;

Adderall XR, an extended release stimulant product providing once-daily dosing, launched in October 2001;

and Mydayis, a stimulant product launched in August 2017.

Other marketed stimulant products for the treatment of ADHD in the U.S.

include the following once-daily formulations:

Qullivant XR, Qullichew ER, Adzenys XR-ODT;

Cotempla XR ODT, Jornay PM, Aptensio XR, Dyanavel XR, Adhansia XR, Evekeo, and Azstarys.

Other marketed non-stimulants in the U.S.

include Strattera and Kapvay.

We are also aware of clinical development efforts by Otsuka, to develop additional treatment options for ADHD.

Otsuka Pharmaceutical Co., Ltd.

announced an agreement with Neurovance, Inc.

to acquire Neurovance, a privately held, venture-funded, clinical stage pharmaceutical company, focused on ADHD and related disorders.

Otsuka is currently conducting Phase III clinical trials to evaluate the efficacy, safety, and tolerability of non-stimulant Centanafadine sustained-release tablets in adults with ADHD.

Sales and Marketing

We, including our subsidiaries, market our products through our own sales forces in the U.S.

and seek strategic collaborations with other pharmaceutical companies to commercialize our products, and those of our subsidiaries, outside of the U.S.

We have a commercial sales and marketing organization in the U.S.

to support sales of our commercial products, and those of our subsidiaries.

We believe our current sales forces are effectively targeting healthcare providers to support and grow our current commercial products, which include the commercial products of our subsidiaries.

As a result of the USWM and Adamas Acquisitions, we established our commercial capabilities in the Parkinson's area with focus on serving movement disorder specialists and other specialized health care providers in the U.S.

With the launch of Qelbree for pediatric patients, we expanded our sales efforts to market the commercial product to the relevant physician audience of psychiatrists, pediatricians, and primary care physicians.

Our sales representatives who supported Trokendi XR and Oxtellar XR now devote their full efforts to the launch of Qelbree.

A smaller contract field force now supports Trokendi XR and Oxtellar XR.

The majority of sales of Oxtellar XR, Trokendi XR, Qelbree, and XADAGO are made to wholesalers and distributors.

In addition, MYOBLOC is available for direct purchase by physicians and hospitals.

The majority of sales of APOKYN and GOCOVRI are made to specialty pharmacies.

Each of our three major customers, AmerisourceBergen Drug Corporation, Cardinal Health, Inc., and McKesson Corporation, individually accounted for more than 25% of our total product revenue in 2021 and collectively accounted for more than 85% of our total product revenue in 2021.

Manufacturing

We, including our subsidiaries, currently depend on third-party commercial manufacturing organizations (CMOs) for all manufacturing operations, including the production of raw materials, dosage form product, and product packaging.

We currently depend on third-party commercial manufacturing organizations (CMOs) for all manufa cturing operations, including the production of raw materials, dosage form product, and product packaging.

This encompasses products for commercial use, as well as some products for preclinical and clinical research.

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We currently employ internal resources to manage our manufacturing contractors.

For our commercial products, including Oxtellar XR, Trokendi XR and Qelbree, we currently rely on single source suppliers for raw materials, including API, and rely on third-party manufacturers for the production and packaging of final commercial products.

We have entered into agreements with leading CMOs headquartered in North America, including Patheon Pharmaceuticals, Inc.

(a subsidiary of Thermo Fisher Scientific Inc.), Packaging Coordinators, Inc., and Catalent Pharma Solutions, for the manufacture and packaging of the commercial products Trokendi XR, Oxtellar XR, Qelbree, as well as for our pipeline product candidates.

With respect to GOCOVRI, Adamas Operations has recently qualified an additional manufacturer of bulk drug substance.

We have agreements with CMOs headquartered North America, including:

Patheon Pharmaceuticals, Inc.

(a subsidiary of Thermo Fisher Scientific Inc.), Packaging Coordinators, Inc., Aphena Pharma Solutions, and Catalent Pharma Solutions, Europe, and Asia for the manufacturing and packaging of some of our commercial products, including those of our subsidiaries, as well as for our pipeline product candidates.

For Qelbree, Trokendi XR, GOCOVRI, and Oxtellar XR we currently rely on third-party CMOs for the manufacturing and packaging of final commercial products.

We rely on third-party CMOs in Asia for the manufacturing of bulk drug substance for Trokendi XR and Oxtellar XR and rely on a third-party CMO in Europe for the raw materials and manufacturing of Qelbree and GOCOVRI.

With respect to GOCOVRI, we have an additional manufacturer of bulk drug substance.

These CMOs offer a comprehensive range of contract manufacturing and packaging services.

The majority of our commercial products, in each case including those of our subsidiaries, are single sourced from third-party suppliers.

APOKYN is manufactured for the U.S.

market by our licensing partner, Britannia.

We purchase APOKYN, MYOBLOC, XADAGO, and Osmolex ER as finished goods.

APOKYN is manufactured and packaged in Europe for the U.S.

market and is supplied to us by our licensing partner, Britannia.

Britannia (a subsidiary of Stada Arzneimittel AG) also supplies injectable apomorphine to the European market under the brand name Apo-go.

MYOBLOC is manufactured and packaged by Merz GmbH & Co.

MYOBLOC is manufactured and packaged in Europe by Merz GmbH & Co.

Under the contract manufacturing agreement with Merz for the manufacture and supply of MYOBLOC, the Company has an annual minimum purchase requirement of MYOBLOC amounting to an estimated €3.9 million.

XADAGO is provided to us as a finished product by Zambon S.p.A.

Osmolex ER is manufactured and packaged by Osmotica Pharmaceutical US LLC (Osmotica), which is the sole manufacturer of Osmolex ER and a subsidiary of Osmotica Pharmaceuticals plc.

Refer to Part I, Item 1A— Risk Factors for risks associated with manufacturing and supply of our products and product candidates.

XADAGO is manufactured and packaged in Europe by Zambon S.p.A.

Osmolex ER is manufactured and packaged in the U.S.

by Osmotica Pharmaceutical US LLC (Osmotica), which is the sole manufacturer of Osmolex ER and a subsidiary of Osmotica Pharmaceuticals plc.

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Refer to Part I, Item 1A — Risk Factors — If we fail to produce our products and product candidates in the volumes that we require on a timely basis or fail to comply with stringent regulations applicable to pharmaceutical drug manufacturers, we may face delays in the development and commercialization of our products and product candidates or be required to withdraw our products from the market for risks associated with manufacturing and supply of our products and product candidates.

Our Proprietary Technology Platforms

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and Namzaric (developed for Allergan plc).

We are also engaged in generating and assessing NCEs.

We are also engaged in generating and assessing New Chemical Entities (NCEs).

These NCEs are generated by leveraging our expertise in structure function relationships in active molecules.

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Intellectual Property and Exclusivity

We, including our subsidiaries, continue to build our intellectual property portfolio to provide protection for our technologies, products, and product candidates.

We, including our subsidiaries, continue to build our intellectual property portfolio to provide protection for our technologies, products, and pr oduct candidates.

We, including our subsidiaries, seek patent protection, where appropriate, both in the U.S.

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For more information, refer to Part I, Item 3—Legal Proceedings in this annual Report on Form 10-K.

We have three families of pending U.S.

non-provisional and foreign counterpart patent applications for Qelbree.

Patents, if issued, could expire from 2029 to 2033.

We have patents issued in the U.S., Canada, and certain countries in Europe covering a method of treating ADHD using viloxazine hydrochloride.

In a second family, covering the novel synthesis process of the active ingredient, we have patents issued in the U.S.

as well as in certain foreign countries.

In a third family, we have four patents issued in the U.S.

covering modified release formulations of viloxazine hydrochloride, three of which cover Qelbree.

We also have patents issued in certain foreign countries.

We own all of the issued patents and the pending patent applications.

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We currently have 10 U.S.

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patents covering Trokendi XR will expire no earlier than 2027.

The Company has entered into settlement agreements with third parties, permitting the sale of a generic version of Trokendi XR on or after January 1, 2023, or earlier under certain circumstances.

The Company has entered into settlement agreements with third parties, permitting the sale of a generic version of Trokendi XR on or after January 1, 2023.

Our extended release oxcarbazepine patent portfolio currently includes 13 U.S.

patents, nine of which cover Oxtellar XR.

The nine issued U.S.

patents, ten of which cover Oxtellar XR.

The ten issued U.S.

patents covering Oxtellar XR will expire no earlier than 2027.

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We also own additional foreign patents for extended release oxcarbazepine.

As an NCE, XADAGO is under the 5 year FDA exclusivity period that expired on March 21, 2022.

As an NCE, XADAGO was under the 5-year FDA exclusivity period that expired on March 21, 2022.

The patent portfolio covering XADAGO has three U.S.

patents licensed from Zambon.

These patents will expire from 2027 and 2031.

We have three families of pending U.S.

non-provisional and foreign counterpart patent applications for Qelbree.

Patents, if issued, could expire from 2029 to 2033.

We have patents issued in Canada, and certain countries in Europe covering a method of treating ADHD using viloxazine hydrochloride.

In a second family, covering the novel synthesis process of the active ingredient, we have patents issued in the U.S.

as well as in certain foreign countries.

In a third family, we have four patents issued in the U.S.

covering modified release formulations of viloxazine hydrochloride, three of which cover Qelbree.

We also have patents issued in certain foreign countries.

We own all of the issued patents and the pending patent applications.

GOCOVRI is currently covered for its FDA-approved indication by a total of 18 issued U.S.

We have additional pending applications containing method and composition claims relating to the pharmacokinetic profile and dosing of amantadine as well as the GOCOVRI formulation.

These issued patents expire through 2038.

These patents and patent applications are wholly owned by Adamas Operations and, as of the first quarter of 2022 are licensed to Supernus Pharmaceuticals, Inc.

We, through our subsidiary Adamas Operations, own additional foreign patents and patent applications covering GOCOVRI.

These patents will expire from 2027 to 2031.

The patent portfolio covering GOCOVRI includes 18 U.S.

We have additional pending applications containing method and composition claims relating to the pharmacokinetic profile and dosing, and formulations of amantadine extended release.

The issued patents expire through 2038.

These patents and patent applications are owned by Adamas Operations and, as of the first quarter of 2022 are licensed to Supernus Pharmaceuticals, Inc.

We, through our subsidiary Adamas Operations, own additional foreign patents and patent applications covering amantadine extended release.

Prior to our acquisition of Adamas, Adamas entered into settlement agreements with third parties, permitting the sale of a generic version of GOCOVRI (amantadine) extended release capsules (including for any new indications approved under the GOCOVRI NDA) on or after March 4, 2030, or earlier under certain circumstances.

Osmolex ER is currently covered for its FDA-approved indications by a total of 18 issued U.S.

patents and additional applications containing method and composition claims relating to the pharmacokinetic profile and dosing of amantadine as well as Osmolex ER formulation.

Osmolex ER is covered for its FDA-approved indications by 18 issued U.S.

patents and additional applications containing method and composition claims relating to the pharmacokinetic profile and dosing, and formulations of amantadine extended release.

These issued patents expire through 2038.

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Adamas Operations also owns additional foreign patents covering Osmolex ER.

Namzaric is covered by a total of 19 of Adamas's issued U.S.

Namzaric is covered by 19 U.S.

patents containing method and compositions claims relating to the pharmacokinetic profile and dosing of memantine.

These patents expire as late as 2029.

Namzaric is currently marketed by Allergan plc under an exclusive license agreement between Adamas and Forest Laboratories Holdings Limited ("Forest"), an indirect, wholly-owned subsidiary of Allergan plc (collectively, "Allergan") in the United States.

Adamas also owns additional foreign patents and patent applications covering Namzaric.

Namzaric is currently marketed by Allergan plc under an exclusive license agreement between Adamas Pharmaceuticals LLC (Adamas Pharmaceuticals) and Forest Laboratories Holdings Limited ("Forest"), an indirect, wholly-owned subsidiary of Allergan plc (collectively, "Allergan") in the United States.

Adamas Pharmaceuticals also owns additional foreign patents and patent applications covering Namzaric.

SPN-830 (apomorphine infusion device)

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patents licensed from Harvard University covering the method of treating seizures to potentially cover our SPN-817 development program.

Additionally, we have filed patent applications in the U.S.

and certain foreign countries for various extended release formulations of huperzine A.

We have one patent issued in the U.S.

and one in China relating to extended release formulations of huperzine.

We additionally have pending patent applications in the U.S.

and certain foreign countries.

SPN-817 has received Orphan Drug designation for both Dravet Syndrome and Lennox-Gastaut Syndrome from the FDA.

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SPN-820 (NV-5138)

Under the terms of the April 2020 Development Agreement with Navitor, we have an exclusive option to license or acquire NV-5138 in all world territories, prior to initiation of the Phase III clinical program.

Patent Application Process

patent system permits the filing of provisional and non-provisional patent applications.

A non-provisional patent application is submitted to the United States Patent and Trademark Office (USPTO) and can mature into a patent once the USPTO determines that the claimed invention meets the standards for patentability.

The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.

In most countries in which we file, the patent term is 20 years from the earliest date of filing a non-provisional patent application.

In the U.S., a patent's term may be lengthened via a patent term adjustment (PTA), which compensates a patentee for administrative delays by the USPTO in granting a patent.

Because of a recent court decision in which the USPTO erred in calculating the PTA by denying the patentee a portion of the patent term to which it was entitled, the USPTO is under greater scrutiny regarding its calculations of PTAs.

Alternatively, a patent's term may be shortened if a patent is terminally disclaimed over another patent.

In evaluating the patentability of a claimed invention, the filing date of a non-provisional patent application is used by the USPTO to determine what information constitutes prior art.

If certain requirements are satisfied, a non-provisional patent application can claim the benefit of the filing date of a previously filed provisional patent application.

In such an instance, the filing date accorded to the provisional patent application may supersede information that otherwise could preclude the patentability of an invention.

The term of a patent that covers an FDA-approved drug may also be eligible for patent term extension (PTE).

This permits the patent term to be extended as compensation for that portion of a patent term lost during the FDA regulatory review process.

The Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Amendments, permits a PTE of up to five years beyond the expiry date of the patent.

The length of the PTE is related to the length of time the drug is under FDA review.

However, the patent extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval.

Only one patent for an approved drug may be extended.

Similar provisions to extend the term of a patent that covers an approved drug are available in Europe and other foreign jurisdictions.

In the future, if and when our pharmaceutical products receive FDA or other regulatory approval, we may be able to apply for PTEs on patents covering those products.

Depending upon the timing, duration, and specifics of FDA approval and the issuance of a U.S.

patent, we may obtain limited patent term restoration.

Other Intellectual Property Rights

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and internationally, where available and when appropriate.

We, including our subsidiaries, have filed for trademark protection for several marks, which are use in connection with our pharmaceutical research and development collaborations as well as with our products and those of our subsidiaries.

We, including our subsidiaries, have filed for trademark protection for several marks, which are used in connection with our pharmaceutical research and development collaborations as well as with our products and those of our subsidiaries.

We or our subsidiaries are the owner/licensee of various U.S.

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We, and our subsidiaries, strive to identify potential third party IP issues in the early stages of our research programs in order to minimize the cost and disruption of resolving such issues.

To protect our competitive position and that of our subsidiaries, it may be necessary to enforce our patent rights through litigation against infringing third parties.

To protect our competitive position and that of our subsidiaries, it may be necessary to enforce our patent rights through litigation aga inst infringing third parties.

See Part I, Item 3—Legal Proceedings .

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See Part I, Item 1A—Risk Factors for risk factors related to intellectual property.