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Item 1. Business

2024-03-05 compared with 2023-02-07 · 163 added, 160 removed, 448 unchanged (42% of the section changed)

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Solidus™ is enabled by our proprietary, computational workflow to discover ASOs with desired drug-like properties to optimize for up/down-regulation, avoidance of toxic motifs and optimization of binding affinity and specificity.

Furthermore, we are collaborating with Cerebral Therapeutics on next-generation, intracerebroventricular, or ICV, CNS delivery technology for select disease targets that necessitate biodistribution to deeper brain areas such as the caudate, striatum and thalamic and subthalamic nucleii.

We believe this will provide a gateway for the advancement of ASOs against targets where others have previously failed or not endeavored to advance.

Led by our clinical-stage product candidate, PRAX-222, Solidus™ has also generated novel ASOs with preclinical proof of mechanism, including PRAX-080, for which we expect to nominate a development candidate for the treatment of PCDH19 in the second half of 2023, PRAX-090 and PRAX-100, and the platform is uniquely positioned to continue discovering and advancing new ASOs for novel genetic CNS targets.

Led by our clinical-stage product candidate, elsunersen (formerly known as PRAX-222), Solidus™ has also generated novel ASOs with preclinical proof of mechanism, including PRAX-080, for which we expect to nominate a development candidate for the treatment of PCDH19 in 2024, PRAX-090, and PRAX-100.

The platform is uniquely positioned to continue discovering and advancing other new ASOs for novel genetic CNS targets.

Below is a summary of our portfolio:

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Our global network of CROs and scientists affords us the flexibility to conduct research and development activities in diverse geographic locations to help accelerate development timelines and limit geographic risks.

We have also solidified our know-how on running hybrid and decentralized clinical trials, increasing our ability to execute our programs with quality and speed, while being closer to patients needs.

Apply patient-guided development strategies.

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We have advanced four product candidates to clinical stage, including three small molecules through the Cerebrum™ platform and one ASO through the Solidus™ platform:

Ulixacaltamide for Essential Tremor and Parkinson’s disease

Our most advanced program, ulixacaltamide, is a differentiated and highly selective small molecule inhibitor of T-type calcium channels currently being studied for the treatment of Essential Tremor, or ET, in a Phase 2b study, and for the treatment of Parkinson’s disease, or PD, in a proof of concept, Phase 2 study.

In ET, ulixacaltamide demonstrated positive results in a Phase 2a study (NCT05021978) in 2022 and the Phase 2b Essential1 study (NCT05021991) is ongoing, with topline results expected in the first quarter of 2023.

Ulixacaltamide Phase 2b Essential1 study

The Essential1 study is a multi-center, randomized, double-blind, placebo-controlled, dose-range finding Phase 2b clinical trial evaluating the efficacy, safety and tolerability of once-daily treatment of ulixacaltamide compared to placebo after 56 days in participants with moderate-to-severe ET.

Approximately 130 participants have been randomized to receive one of two titrated, fixed-dose regimens for 56 days (60 or 100 mg) or placebo, administered orally every morning.

The primary endpoint for Essential1 is change from baseline to Day 56 in the modified Activities of Daily Living, or mADL, score, the suggested efficacy endpoint for ET by the U.S.

Food and Drug Administration, or the FDA.

The mADL endpoint is a composite measure of tremor-related activities over the previous week that assesses the direct impact of ET on the lives of patients.

The mADL endpoint is functionally relevant for people living with ET, representing a modified measure of the Essential Tremor Rating Assessment Scale, or TETRAS, ADL subscale with the addition of two items from the TETRAS performance section, or PS .

Ulixacaltamide Phase 2 study for PD

We plan to initiate a randomized, double-blind, placebo-controlled Phase 2 trial to evaluate the efficacy, safety and tolerability of once-daily treatment of up to 100 mg of ulixacaltamide as a non-dopaminergic treatment for the motor symptoms of PD in the first quarter of 2023.

The primary endpoint will be change from baseline in the International Parkinson and Movement Disorder Society Unified Parkinson’s Disease Rating Scale, or UPDRS, Part III (motor examination) score in the OFF state.

Topline results are expected in the fourth quarter of 2023.

Ulixacaltamide for Essential Tremor

Our most advanced program, ulixacaltamide, is a differentiated and highly selective small molecule inhibitor of T-type calcium channels currently in Phase 3 clinical development for the treatment of Essential Tremor, or ET.

Additionally, we have an exclusive collaboration and license agreement with Tenacia Biotechnology (Shanghai) Company, Ltd., a China-based portfolio company of Bain Capital, to develop and commercialize ulixacaltamide for the treatment of ET in China, Hong Kong, Macau and Taiwan.

Ulixacaltamide Phase 3 Essential3 trial

Essential3 is a decentralized, Phase 3, multi-study, clinical trial evaluating the safety and efficacy of 60 mg of ulixacaltamide in ET.

The study includes two separate and simultaneous Phase 3 pivotal studies, of which one is a 12-week parallel design and the other a 12-week randomized withdrawal design, with all participants undergoing one screening process and a long-term safety study, or LTSS.

The study uses the modified Activities of Daily Living 11, or mADL11, as the primary endpoint.

Enrollment for the Phase 3 trials is expected to be completed in the first half of 2024, with topline results expected in the second half of 2024 to support a potential New Drug Application, or NDA, submission in 2025.

Essential1 study

The Essential1 study was a multi-center, randomized, double-blind, placebo-controlled, dose-range finding Phase 2b clinical trial evaluating the efficacy, safety and tolerability of once-daily treatment of ulixacaltamide compared to placebo after 56 days in participants with moderate-to-severe ET.

Topline results for the Phase 2b Essential1 study were announced in the first quarter of 2023.

Results of the Essential1 study informed an end-of-Phase 2 meeting with the FDA and the design of the Phase 3 Essential3 program.

Essential Tremor

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ET is characterized by involuntary rhythmic movements in the upper limbs that significantly disrupt ability to function and are progressive in nature.

There is only one approved pharmacotherapy for ET, a beta blocker (propranolol), approved by the FDA in 1967, that offers limited efficacy and poor tolerability and is contraindicated for comorbidities that affect a significant share of the ET population.

There is only one approved pharmacotherapy for ET, a beta blocker (propranolol), approved by the FDA for ET in 1986, that offers limited efficacy and poor tolerability and is contraindicated for comorbidities that affect a significant share of the ET population.

Other CNS drugs are used off-label, though similarly are characterized by limited efficacy and poor tolerability.

For these reasons, approximately 40% of patients who seek pharmacotherapy treatment discontinue within two years.

As a last line therapy, a small subset of patients will opt for invasive procedures such as gamma knife and MRI guided focused ultrasound thalamotomy, where part

of the thalamus involved in the cerebello-thalamo-cortical, or CTC, circuit is ablated, or deep brain stimulation, or DBS, where an electrode is implanted to deliver therapeutic electrical stimulation to the thalamus.

As a last line therapy, a small subset of patients will opt for invasive procedures such as gamma knife and MRI guided focused ultrasound thalamotomy, where part of the thalamus involved in the cerebello-thalamo-cortical, or CTC, circuit is ablated, or deep brain stimulation, or DBS, where an electrode is implanted to deliver therapeutic electrical stimulation to the

While these procedures are generally effective, they are associated with significant side effects and risk.

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In totality, there is significant unmet need for an effective and tolerable pharmacotherapy targeted for ET.

Parkinson’s Disease

PD is the second most common movement disorder behind ET, with approximately one million diagnosed patients in the United States and 10 million patients worldwide.

Roughly 60,000 patients are diagnosed with PD each year in the United States alone.

PD is characterized by slow movement (bradykinesia), in combination with either rest tremor and/or rigidity.

Symptoms progress over time in severity and eventually affect both sides of the body, often impairing ADLs such as dressing and eating.

Non-motor symptoms, such as impaired smell, sleep disorders, gastrointestinal symptoms and psychiatric disorders like depression also play a pivotal role in the daily life of PD patients.

The cornerstone of treatment for PD has been dopaminergic replacement therapy.

L-dopa, or levodopa, a formulation of replacement dopamine, is considered the standard treatment of PD.

Levodopa has been shown to be highly effective in improving symptoms of bradykinesia and rigidity, but has a variable impact on tremor.

Other common PD medications mainly reduce dopamine metabolism or are dopamine receptor agonists.

While chronic dopaminergic therapy is effective, it can result in distressing side effects of motor fluctuations (wearing off) and levodopa-induced dyskinesias, impulse control disorders and psychosis.

These side effects are disabling and, at times, more severe and distressing than the PD symptoms themselves.

Patients may also opt for a more invasive procedure to deliver continuous dopamine stimulation with levodopa-carbidopa enteral suspension to continuously control motor fluctuations and dyskinesias.

DBS is typically reserved for those patients who respond to dopaminergic therapy, like levodopa, but have residual symptoms.

Further, DBS carries significant risks associated with brain surgery, including intracerebral hemorrhage, infection, hemiparesis and cognitive decline.

The prospect of neurosurgery in later years is often overwhelming or contraindicated ( e.g.

, due to presence of cognitive impairment), and many patients are not treated with DBS.

Therefore, we believe there is significant unmet need for an effective and tolerable treatment for motor symptoms associated with PD.

PRAX-562 for rare, monogenic DEEs

PRAX-628 for Focal Epilepsy

PRAX-628 is a next-generation, functionally selective small molecule targeting the hyperexcitable state of sodium-channels in the brain and is currently being developed as a once daily, oral treatment for adult focal onset epilepsy.

Preclinical data demonstrates PRAX-628 is differentiated from standard of care, with the potential to be best-in-class for focal epilepsy.

In vitro, PRAX-628 has demonstrated superior selectivity for disease-state NaV channel hyperexcitability.

In vivo studies of PRAX-628 have demonstrated unprecedented potency in the maximal electroshock seizure, or MES, model, a highly predictive translational model for efficacy in focal epilepsy.

Data from the PRAX-628 Phase 1 study demonstrated that PRAX-628 was well tolerated in healthy subjects at greater than 15 times the predicted human equivalent of the mouse MES,EC 50 .

We intend to initiate a Phase 2b study of PRAX-628 in focal epilepsy in the second half of 2024.

PRAX-628 Phase 2a Photo-Paroxysmal Response study

We are conducting a Phase 2a Photo-Paroxysmal Response, or PPR, study to evaluate the efficacy and safety of PRAX-628 across two cohorts, dosed at 15 mg and 45 mg.

PPR studies measure EEG signatures after intermittent photic stimulation and are widely used as a marker of anti-seizure efficacy and to aid in dose determination.

We believe this approach has been validated with several approved and new therapies.

A preliminary analysis of the 15 mg cohort completed in January 2024 showed that this cohort exceeded our expectations in terms of drug activity.

Topline results, including data from the ongoing 45 mg cohort, are anticipated in the first quarter of 2024.

PRAX-628 Phase 1 first-in-human study

We initiated a Phase 1 healthy volunteer study of PRAX-628 in the fourth quarter of 2022 to evaluate the tolerability, pharmacokinetics, or PK, pharmacodynamics, or PD, and food effect of PRAX-628 across single and multiple ascending dose cohorts.

Topline results from the study were announced in the second quarter of 2023.

This first clinical study of PRAX-628 was a randomized, double-blind, placebo-controlled single ascending dose, or SAD, and multiple ascending dose, or MAD, trial in healthy participants aged 18-55 years.

Interim analysis from Part A (SAD, 5 to 45 mg) and Part B (MAD, 20 to 30 mg) demonstrated drug plasma exposure increases with both dose and time.

The concentrations achieved exceeded the predicted efficacious level based on the mouse MES EC 50 and were reached in all cohorts.

In the SAD cohorts, average concentrations 2-4x the MES EC 50 were maintained for 8 hours with a single dose of 15 mg.

In the MAD cohorts, concentrations in excess of 15x the MES EC 50 were achieved at C max with average C trough around 3-5x the MES EC 50 at steady-state.

PRAX-628 was well tolerated with no serious adverse events, or SAEs, observed at repeated doses up to 30 mg/day for 10 days.

No adverse events, or AEs, or AEs of special interest led to study drug withdrawal, and no clinically significant findings on vital signs, electrocardiogram or neurological examination were observed.

All AEs were mild, mostly transient (lasting minutes to hours), and resolved spontaneously, with the most common AEs being CNS-related.

Focal Epilepsy

Focal epilepsy is the most common type of epilepsy, accounting for approximately 60% of all cases.

In the United States alone, it is estimated that focal epilepsy affects approximately two million people.

Focal epilepsy is characterized by seizures that originate in one side or area of the brain and affects one side of the body.

Focal epilepsy patients are treated with sodium channel targeting antiepileptic drugs, or AEDs, such as Tegretol (carbamazepine), Lamictal (lamotrigine), Xcopri (cenobamate) and many others.

However, despite the plethora of marketed treatments, up to 30% of patients remain refractory to treatment.

There are two forms of therapeutically relevant sodium current:

(1) persistent sodium current and (2) peak sodium current.

Standard of care sodium channel targeting AEDs can produce severe toxicity at therapeutic doses from excessive inhibition of peak sodium current, as physiological levels of peak sodium current are required for normal neuronal function.

Therefore, novel compounds that inhibit persistent and peak sodium channel hyperexcitability while sparing physiological levels of peak sodium current may improve clinical efficacy and tolerability.

PRAX-562 for rare, monogenic Developmental and Epileptic Encephalopathies

PRAX-562 is a first-in-class preferential inhibitor of persistent sodium current, presently in development for the treatment of rare developmental and epileptic encephalopathies, or DEEs.

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PRAX-562 Phase 2 EMBOLD study

In November 2022, we announced plans to initiate the PRAX-562 Phase 2 EMBOLD study for the treatment of pediatric patients with DEEs, following FDA authorization to proceed with the study as we proposed, up to the planned maximum dose of 1.0 mg/kg/day.

The study is expected to initiate in the first quarter of 2023, with two cohorts in early-onset SCN2A-DEE and SCN8A-DEE patients.

In the first quarter of 2023, we initiated the PRAX-562 Phase 2 EMBOLD study for the treatment of pediatric patients with DEEs, with two cohorts in early-onset SCN2A-DEE and SCN8A-DEE patients.

The EMBOLD study is a randomized, double-blind, placebo-controlled Phase 2 clinical trial to evaluate the safety, tolerability, efficacy (motor seizure frequency) and PK of PRAX-562 in pediatric participants aged 2 to 18 years with DEEs, followed by an open-label extension.

Approximately 20 participants will be enrolled initially in two distinct cohorts ([n≈10 for SCN2A-DEE and n≈10 for SCN8A-DEE]).

Topline results for both cohorts are expected in the second half of 2023.

Topline results for both cohorts are expected in mid-year 2024.

Rare, monogenic DEEs

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Hyperexcitability can lead to abnormal synchronization of neurons and neuronal circuits, which is the electrical basis of a seizure.

Fundamentals of brain electrophysiology and mechanisms dictating seizure genesis are conserved across species and, consequently, animal models of seizures and epilepsy enable a clinically predictive and

therefore efficient drug development path.

A subset of epilepsies are rare, monogenic DEEs characterized by early onset (less than 2 years of age), frequent seizures, abnormal epileptiform EEG activity, developmental impairment and resistance to available antiepileptic drugs, or AEDs.

Furthermore, these DEEs are associated with a high mortality rate and comorbidities such as developmental delay in addition to behavioral disorders, movement disorders, pain and sensory dysfunction and sleep disruptions.

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While standard-of-care sodium channel blockers inhibit persistent sodium current, they also block peak sodium current at therapeutic concentrations, which can cause significant adverse events, or AEs, such as ataxia, drowsiness and dizziness, and therefore have a very narrow Therapeutic Index, or TI, resulting in subpar outcomes for patients and significant need for better therapeutic options.

We believe that there is a significant medical unmet need in DEEs, coupled with an untapped and significant market opportunity for targeted drugs.

Early onset SCN2A-DEE is a rare condition caused by a gain-of-function, or GoF, variant in the SCN2A gene.

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Despite these interventions, it is estimated that more than 80% of early-onset SCN2A-DEE patients live with uncontrolled seizures, and approximately 75% live with severe intellectual disability.

It is estimated that there are at least 1,500 patients in the United States with GoF changes in SCN2A leading to epileptic encephalopathy.

It is estimated that there are approximately 2,000 patients in the United States with GoF changes in SCN2A leading to epileptic encephalopathy.

SCN8A-DEE is a rare DEE caused by a gain-of-function variant in the SCN8A gene.

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SCN8A-DEE patients also may experience autonomic features such as increases or decreases in heart rate, abnormal breathing and cyanosis.

It is estimated that there are at least 1,000 patients in the United States with SCN8A-DEE.

PRAX-222 for SCN2A-DEE

PRAX-222 is a clinical-stage ASO designed to down-regulate Na V 1.2 expression, an effect that has demonstrated disease-modifying activity in animal models of SCN2A epileptic encephalopathy.

It is estimated that there are approximately 2,000 patients in the United States with SCN8A-DEE.

Elsunersen for SCN2A-DEE

Elsunersen is a clinical-stage ASO designed to down-regulate Na V 1.2 expression, an effect that has demonstrated disease-modifying activity in animal models of SCN2A epileptic encephalopathy.

In transgenic mice carrying a human SCN2A GoF mutation, we observed a significant, dose-dependent reduction in seizures and increased survival of mice treated with a mouse ASO that is designed to down-regulate SCN2A.

The survival benefit from the ASO was maintained with repeat dosing.

We also observed survival benefits following administration of a

mouse ASO to a group of mice after onset of disease and around the time of onset of mortality.

PRAX-222 has received ODD and RPD from the FDA, and ODD from the EMA for the treatment of SCN2A-DEE.

PRAX-222 EMBRAVE study

In September 2022, we announced plans to initiate the PRAX-222 EMBRAVE study for the treatment of pediatric patients with early-onset SCN2A-DEE, after the FDA allowed us to proceed under an Investigational New Drug, or IND, application for the initial dose cohort, or Part 1 of the study.

Following collection of the safety and efficacy data from Part 1, the data will be evaluated and submitted to the FDA to support further dose escalation.

Part 1 of the EMBRAVE study is a 21-week open label cohort, in which participants will receive PRAX-222 for up to 13 weeks, designed to determine the safety and tolerability of intrathecal delivery of PRAX-222.

We expect topline results from the first dose cohort of the PRAX-222 EMBRAVE study in mid-2023.

PRAX-628 for Focal Epilepsy

PRAX-628 is a potential best-in-class sodium channel blocker designed with enhanced targeting of both the persistent sodium current and disease-state dependent peak sodium current hyperexcitability, being developed for the treatment of focal epilepsy.

In vivo studies have demonstrated best-in-class potency across preclinical disease models that have shown strong historical translation to the clinic.

PRAX-628 Phase 1 first-in-human study

We initiated a Phase 1 healthy volunteer study of PRAX-628 in the fourth quarter of 2022 to evaluate the tolerability, PK, pharmacodynamics and food effect of PRAX-628 across single and multiple ascending dose cohorts.

We expect to report topline results from the Phase 1 study in mid-2023 and subsequently initiate a Phase 2 study in focal epilepsy in the fourth quarter of 2023.

Focal Epilepsy

Focal epilepsy is the most common type of epilepsy, accounting for approximately 60% of all cases.

In the United States alone, it is estimated that focal epilepsy affects approximately two million people.

Focal epilepsy is characterized by seizures that originate in one side or area of the brain and affects one side of the body.

Focal epilepsy patients are treated with sodium channel targeting AEDs, such as Tegretol (carbamazepine), Lamictal (lamotrigine), Xcopri (cenobamate) and many others.

However, despite the plethora of marketed treatments, up to 30% of patients remain refractory to treatment.

There are two forms of therapeutically relevant sodium current:

(1) persistent sodium current and (2) peak sodium current.

Therefore, novel compounds that inhibit persistent and peak sodium channel hyperexcitability while sparing physiological levels of peak sodium current may improve clinical efficacy and tolerability.

We also observed survival benefits following administration of a mouse ASO to a group of mice after onset of disease and around the time of onset of mortality.

Elsunersen has received ODD and RPD from the FDA, and ODD and PRIority MEdicines, or PRIME, designation from the EMA for the treatment of SCN2A-DEE.

Elsunersen EMBRAVE study

In the second quarter of 2023, we initiated the EMBRAVE study for the treatment of pediatric patients with early-onset SCN2A-DEE, after the FDA allowed us to proceed under an Investigational New Drug, or IND, application for the initial dose cohort, or Part 1 of the study.

Part 1 of the EMBRAVE study was a 21-week open label cohort, in which participants received elsunersen for up to 13 weeks, designed to determine the safety and tolerability of intrathecal delivery of elsunersen.

Dosing for Part 1 of the EMBRAVE study was completed in the fourth quarter of 2023.

No treatment related AEs or SAEs were observed.

Additionally, patients observed a marked reduction in seizures and increase in seizure-free days.

We are completing multiple global regulatory interactions in the first quarter of 2024 in anticipation of starting the pivotal phase of the program later this year.

The biopharmaceutical industry is characterized by rapidly advancing technologies, strong competition and an emphasis on proprietary products.

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Our competitors fall primarily into the following groups of treatment:

• T-type calcium channel inhibitor programs in development targeting ET, including that of Jazz Pharmaceuticals, as well as other programs in clinical development targeting other mechanisms of action and approved therapies, such as propranolol, and off-label therapies, such as primidone.

• Sodium channel blocker or similar programs in development for DEEs, including those of SK-Pharma, Xenon Pharmaceuticals, Neurocrine Biosciences and Stoke Therapeutics, as well as other programs in clinical development targeting other mechanisms of action and approved therapies including other existing ion channel blockers.

• T-type calcium channel inhibitor programs in development targeting ET, including that of Jazz Pharmaceuticals, as well as other programs in clinical development targeting other mechanisms of action such as GABA by Sage Therapeutics, and approved therapies, such as propranolol, and off-label therapies, such as primidone.

• Sodium channel blocker or similar ion channel-targeting programs in development for focal epilepsy, including those of SK-Pharma, Xenon Pharmaceuticals, and Biohaven Pharmaceuticals, as well as other programs in clinical development targeting other mechanisms of action including those from Longboard Pharmaceuticals, Marinus Pharmaceuticals and Stoke Therapeutics, and approved therapies including other existing ion channel blockers.

Many of our competitors have substantially greater financial resources, expertise and capabilities in research and development, the regulatory approval process, manufacturing and marketing than we do.

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T-type Calcium channel blockers

We own six patent families directed to T-type Calcium channel blockers.

We own twelve patent families directed to T-type Calcium channel blockers.

One patent family discloses and claims compositions of matter of certain T-type calcium channel modulators, including ulixacaltamide.

This patent family has issued in many major pharmaceutical markets and is pending in others and expires in 2029.

A second family is directed to methods of use of certain T-type calcium channel modulators, including ulixacaltamide, in treating disease such as epilepsy.

This patent family is pending in the United States and expires in 2037.

A third patent family is directed to certain pharmaceutical formulations of ulixacaltamide and methods of use in treating disorders such as essential tremor.

This patent family is pending in multiple jurisdictions of potential commercial interest and expires in 2040.

A fourth family is directed to titration methods of using ulixacaltamide and expires in 2041.

A fifth patent family is directed to certain analog compounds of ulixacaltamide and expires in 2040.

The sixth patent family is directed to the adjunctive use of a beta blocker and/or certain anticonvulsants with ulixacaltamide and expires in 2043.

A second patent family is directed to certain pharmaceutical formulations of ulixacaltamide and methods of use in treating disorders such as essential tremor.

patents have issued in this patent family, and expire in 2040, and this family remains pending in multiple jurisdictions of potential commercial interest.

A third family is directed to titration methods of using ulixacaltamide and expires in 2041.

A fourth patent family is directed to certain analog compounds of ulixacaltamide and expires in 2040.

A fifth patent family is directed to the adjunctive use of a beta blocker and/or certain anticonvulsants with ulixacaltamide and expires in 2043.

A sixth patent family is directed to a dosage form of ulixacaltamide and expires in 2044.

A seventh patent family is directed to salt forms of ulixacaltamide and expires in 2044.

An eighth patent family is directed to crystalline forms of ulixacaltamide and expires in 2044.

A ninth patent family is directed to methods of treatment using ulixacaltamide and expires in 2044.The remaining patent families are directed to other TTCC blockers of various core structures and methods of use in treating diseases such as movement disorders, which expire in 2039 and 2040.

Persistent sodium current blockers

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One patent family discloses and claims certain persistent sodium current blockers, including PRAX-562 and PRAX-628, and methods of use in treating diseases such as epilepsy (including pediatric epilepsy), as well as migraine and pain.

In this patent family, PRAX-562 is covered by a patent that has granted in the United States (U.S.

11,014,931), and patent applications pending in other potentially commercially relevant jurisdictions, which expire in 2039.

In this patent family, PRAX-562 is covered by a patent that has granted in the United States, and patent applications pending in other potentially commercially relevant jurisdictions, which expire in 2039.

In this same patent family, PRAX-628 is covered by two granted U.S.

patents that will expire in 2039.

A second family discloses other persistent sodium current blockers and generically claims PRAX-562, as well as methods of treating diseases such as pediatric epilepsy.

This patent family is pending in multiple jurisdictions and expires in 2037.

A third family is directed to pharmaceutical formulations of PRAX-562, methods of use in treating diseases such as pediatric

epilepsy, cephalgia, short-lasting unilateral neuralgiform headache attacks with conjunctival injection, or SUNCT, and tearing and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms, or SUNA, and methods of making PRAX-562, and expires in 2040.

A third family is directed to pharmaceutical formulations of PRAX-562, methods of use in treating diseases such as pediatric epilepsy, cephalgia, short-lasting unilateral neuralgiform headache attacks with conjunctival injection, or SUNCT, and tearing and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms, or SUNA, and

methods of making PRAX-562, and expires in 2040.

The remaining patent families are directed to other persistent sodium current blockers of various core structures and methods of use in treating diseases such as pediatric epilepsy, expiring between 2037 and 2043.

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KCNT1 blockers

We own eleven patent families directed to KCNT1 blockers including ten families related to our KCNT1 program and one family related to ASOs.

Ten patent families disclose and claim small molecule KCNT1 blockers and methods of use in treating diseases such as epilepsy, including epilepsy having certain KCNT1 mutations, and expire between 2040 and 2043.

One patent family is directed to certain ASOs and methods of use in treating diseases such as epilepsy, including epilepsy having certain KCNT1 mutations, and expires in 2039.

We own sixteen patent families directed to KCNT1 blockers.

These patent families disclose and claim small molecule KCNT1 blockers and methods of use in treating diseases, such as epilepsy, including epilepsy having certain KCNT1 mutations, and expire between 2040 and 2043.

GABA A receptor positive allosteric modulators

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One patent family discloses and claims salts and polymorphs of PRAX-114.

Two patents are granted in the United States (U.S.

10,562,930 and U.S.

10,927,141), which expire in 2039.

A second patent family is directed to alternative salt forms of PRAX-114, which expires in 2042.

Other patent applications cover methods of use and processes for making related to PRAX-114, which expire from 2041 to 2043.

Two patents are granted in the United States, which expire in 2039.

A second patent family is directed to alternative salt forms of PRAX-114, and a U.S.

patent has issued, which expires in 2042.

Other patent applications cover processes for making related to PRAX-114 and methods of use in treating diseases (including the use of combination formulations), such as epilepsy, major depressive disorder, musculoskeletal conditions, motor disorder or essential tremor, which expire from 2042 to 2043.

LICENSE AGREEMENTS

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The $3.0 million milestone payment will become due when (i) the first profit share payment has become due and payable and (ii) the Additional Milestone, the Initial Interest Amount and the Second Interest Amount (each as defined within the Ionis Agreement as described below) have all become due and payable to Ionis under our collaboration agreement with Ionis.

As part of the RogCon Agreement, we agreed to provide up-front consideration of $2.1 million, consisting of a $1.0 million deposit, $0.7 million in cash reimbursements for certain historical costs

previously incurred by RogCon and $0.4 million for the retirement of existing loan balances as of September 11, 2019.

As part of the RogCon Agreement, we agreed to provide up-front consideration of $2.1 million, consisting of a $1.0 million deposit, $0.7 million in cash reimbursements for certain historical costs previously incurred by RogCon and $0.4 million for the retirement of existing loan balances as of September 11, 2019.

Subsequent to September 11, 2019, we will reimburse RogCon for its out-of-pocket costs incurred for activities performed under the RogCon Agreement.

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Upon the occurrence of one of these three payment triggers, both the Initial Interest Amount and Second Interest Amount are due and payable to Ionis.

In the second quarter of 2023, Ionis earned the Additional Milestone fee of $5.0 million, as well as the Initial Interest Amount of $1.9 million.

The $6.9 million milestone fee was paid in July of 2023.

The Ionis Agreement will continue in full force and effect until the expiration of all payment obligations to Ionis, unless terminated earlier by either party.

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For clinical supply, we rely on CDMOs to manufacture drug substance and drug product in accordance with the FDA’s current Good Manufacturing Practices, or cGMP.

We expect to rely on third parties for our manufacturing

processes and the production of all clinical supply drug substance and drug product and currently expect to continue to do so for commercial supplies of our product candidates, if approved.

We expect to rely on third parties for our manufacturing processes and the production of all clinical supply drug substance and drug product and currently expect to

continue to do so for commercial supplies of our product candidates, if approved.

We use additional contract manufacturers to fill, label, package, store and distribute our investigational drug products and currently expect to continue to do so for commercial supplies of our product candidates, if approved.

It is our intent to identify and qualify additional manufacturers to provide active pharmaceutical ingredient and fill-and-finish services prior to submission of a new drug application, or NDA, to the FDA for any product candidates that complete clinical development.

It is our intent to identify and qualify additional manufacturers to provide active pharmaceutical ingredient and fill-and-finish services prior to submission of a NDA to the FDA for any product candidates that complete clinical development.

GOVERNMENT REGULATION

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An IND is a request for authorization from the FDA to administer an investigational product to humans and must become effective before human clinical trials may begin.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed

clinical trial.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial.

In such a case, the IND may be placed on clinical hold and the IND sponsor and the FDA must resolve any outstanding concerns or questions before the clinical trial can begin.

Submission of an IND therefore may or may not result in FDA authorization to begin a clinical trial.

Submission of an IND therefore may or

may not result in FDA authorization to begin a clinical trial.

Additionally, the FDA will review any data from clinical trials conducted outside the United States when determining whether to allow an IND to proceed in the United States.

Specifically, the FDA’s acceptance of data from trials conducted outside of the United States and not under an IND is subject to certain conditions, including that the clinical trial must be well designed and conducted in accordance with GCPs, and the FDA must be able to validate the data from the study through an on-site inspection, if necessary.

Specifically, the FDA’s acceptance of data from trials conducted outside of the United States and not under an IND is subject to certain conditions, including that the clinical trial must be conducted in accordance with GCPs, and the FDA must be able to validate the data from the study through an on-site inspection, if necessary.

Clinical holds also may be imposed by the FDA at any time before or during studies due to safety concerns or non-compliance.

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A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND.

While the IND is active, progress reports summarizing the results of clinical trials and nonclinical studies, 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 if serious and unexpected suspected adverse events occur, findings from other studies of the same or similar drug or from animal or in vitro testing suggest a significant risk, or there is an increased incidence of a serious suspected adverse reaction compared to that in the protocol or investigator brochure.

Furthermore, an independent IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site, and must monitor the study until completed.

Some studies also include oversight by an independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study, and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

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

An IRB can also suspend or terminate approval of a clinical trial at its institution for a variety of reasons, including if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients.

There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries.

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In Phase 2, the product candidate is administered to a limited patient population with a specified disease or condition to evaluate possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for the specified disease or condition, and to determine dosage tolerance and optimal dosage.

In Phase 3, the product candidate is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the product candidate for approval, to establish the overall risk-benefit profile of the product candidate, and to provide adequate information for the labeling of the product candidate.

In Phase 3, the product candidate is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to provide substantial evidence of the efficacy and safety of the product candidate, to establish the overall risk-benefit profile of the product candidate, and to provide adequate information for the labeling of the product candidate.

In some cases, the FDA may require, or sponsors may voluntarily pursue, additional clinical trials after a product is approved to gain more information about the product.

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In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition or requirement of approval of an NDA.

Progress reports summarizing the results of clinical trials and nonclinical studies, 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 if serious and unexpected suspected adverse events occur, findings from other studies of the same or similar drug or from animal or in vitro testing suggest a significant risk, or there is an increased incidence of a serious suspected adverse reaction compared to that in the protocol or investigator brochure.

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

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution for a variety of reasons, including if the clinical trial is not being conducted

in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients.

Concurrent with clinical trials, companies usually complete additional animal studies and also must develop additional information about the chemistry and physical characteristics of the drug as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

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Once an application is accepted for filing, the FDA has a goal of ten months from the date of “filing” to complete a standard review of an NDA for a drug that is a new molecular entity, and six months from the filing date to complete a priority review.

The FDA does not always meet its goal dates, and the review process can be extended by FDA requests for additional information or clarification and a sponsor’s process to respond to such inquiries.

The FDA does not always meet its goal dates, and the review process can be extended for a three-month period by the FDA to review information deemed a "major amendment" to the application.

This FDA review process typically takes 10 months from the date the NDA is accepted for filing by the FDA (for a standard review) or six months from the filing date (for a priority review).

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The sponsor or FDA may request a deferral of pediatric clinical trials for some or all of the pediatric subpopulations.

The FDA must send a non-compliance letter

to any sponsor that fails to submit the required assessment, keep a deferral current or fails to submit a request for approval of a pediatric formulation.

After evaluating the NDA and all related information, including the advisory committee recommendation, if any, and inspection reports regarding the manufacturing facilities, sponsor, and clinical trial sites, the FDA may issue either an approval letter or a complete response letter, or CRL.

The FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, keep a deferral current or fails to submit a request for approval of a pediatric formulation.

After evaluating the NDA and all related information, including the advisory committee recommendation, if any, and any inspection reports regarding the manufacturing facilities, sponsor, and clinical trial sites, the FDA may issue either an approval letter or a complete response letter, or CRL.

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

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

A company must request orphan drug designation before submitting an NDA.

A sponsor must request orphan drug designation before submitting an NDA.

If the request is granted, the FDA will disclose the identity of the therapeutic agent and its potential use.

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Orphan product exclusivity means that the FDA may not approve any other applications for the same product for the same disease or condition for seven years.

If a drug or drug product designated as an orphan product ultimately receives marketing approval for an indication broader than what was designated in its orphan product application, it may not be entitled exclusivity.

Orphan exclusivity will not bar approval of another product under certain circumstances, including if a subsequent product with the same active ingredient for the same indication is shown to be clinically superior to the approved product on the basis of greater efficacy or safety, or to provide a major contribution to patient care, or if the company with orphan drug exclusivity is not able to meet market demand.

If a drug or drug product designated as an orphan product ultimately receives marketing approval for a disease or condition broader than what was designated in its orphan product application, it may not be entitled exclusivity.

Orphan exclusivity will not bar approval of another product under certain circumstances, including if a subsequent product with the same active ingredient for the same disease or condition is shown to be clinically superior to the approved product on the basis of greater efficacy or safety, or to provide a major contribution to patient care, or if the company with orphan drug exclusivity is not able to meet market demand.

Among the other benefits of orphan drug designation are tax credits for certain research and a waiver of the NDA application user fee.

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and (b) rare diseases or conditions within the meaning of the Orphan Drug Act.

Congress has only authorized the Rare Pediatric Disease Priority Review Voucher program until September 30, 2024.

Congress has only authorized the Rare Pediatric

Disease Priority Review Voucher program until September 30, 2024.

Consequently, sponsors of marketing applications approved after that date will not receive the voucher unless Congress reauthorizes the program.

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Such product candidates can be approved upon a determination that the product candidate has an effect on either a surrogate endpoint that is reasonably likely to predict clinical benefit or on an intermediate clinical endpoint that can be measured earlier than irreversible morbidity or mortality, or IMM, that is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity, or prevalence of the disease or condition and the availability or lack of alternative treatments.

As a condition of approval, the FDA generally requires that a sponsor of a drug receiving accelerated approval perform adequate and well-controlled confirmatory clinical trials to verify and describe the predicted effect on IMM or other clinical endpoint.

The FDA may withdraw approval of a drug or indication approved under accelerated approval on an expedited basis if, for example, the confirmatory trial fails to verify the predicted clinical benefit of the product or the sponsor fails to conduct such confirmatory trials in a timely manner or in accordance with applicable regulations.

Drugs granted accelerated approval must meet the same

statutory standards for safety and effectiveness as those granted traditional approval.

Drugs granted accelerated approval must meet the same statutory standards for safety and effectiveness as those granted traditional approval.

In addition, all promotional materials for products approved under the accelerated approval program are subject to prior review by the FDA.

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However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement.

The FDCA also provides three years of marketing exclusivity when an NDA, or a supplement to an existing NDA, includes new clinical investigations, other than bioavailability studies, conducted or sponsored by the applicant that are deemed by the FDA to be essential to the approval of the application, for example, new indications, dosages or strengths of an existing drug.

The FDCA also provides three years of non-patent exclusivity when an NDA, or a supplement to an existing NDA, includes new clinical investigations, other than bioavailability studies, conducted or sponsored by the applicant that are deemed by the FDA to be essential to the approval of the application, for example, new indications, dosages or strengths of an existing drug.

This three-year exclusivity covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs or follow-on 505(b)(2) NDAs if the protected clinical data are not referenced.

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Pediatric exclusivity is another type of regulatory market exclusivity in the United States.

Pediatric exclusivity, if granted, adds six months to existing regulatory exclusivity periods.

Pediatric exclusivity, if granted, adds six months to existing regulatory exclusivity periods or patent terms.

This six-month exclusivity may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial.

The FDA's issuance of a written request does not obligate the sponsor to complete the requested pediatric studies.

Post-approval requirements

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

Further, prior to the U.S.

Supreme Court ruling, President Biden issued an executive order to, among other things, instruct certain governmental agencies to review and reconsider their existing policies and rules that limit access to health care, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.

In addition, other legislative changes have been proposed and adopted in the United States since the ACA was enacted.

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On January 2, 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers, including hospitals and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

Moreover, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.

Moreover, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminated the statutory Medicaid drug rebate cap for single source and innovator multiple source drugs, beginning January 1, 2024.

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

Payment methodologies may also be subject to changes in healthcare legislation and regulatory initiatives.

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

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

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

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.

HHS has and will continue to issue and update guidance as these programs are implemented.

These provisions started to take effect progressively starting in fiscal year 2023.

On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges.

In addition, in response to the Biden administration’s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the Center for Medicare and Medicaid Innovation which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care.

It is unclear whether the models will be utilized in any health reform measures in the future.

At the state level, legislatures in the United States have also increasingly passed legislation and implemented 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, designed to encourage importation from other countries and bulk purchasing.

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Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which we obtain regulatory approval.

Sales of any products for which we receive regulatory approval for commercial sale will depend, in part, on the extent to which third-party payors provide coverage and establish adequate reimbursement levels for such drug products.

In the United States, third-party payors include federal and state healthcare programs, government authorities, private manage care providers, private health insurers and other

organizations.

Sales of any products for which we receive regulatory approval for commercial sale

will depend, in part, on the extent to which third-party payors provide coverage and establish adequate reimbursement levels for such drug products.

In the United States, third-party payors include federal and state healthcare programs, government authorities, private manage care providers, private health insurers and other organizations.

For products administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs.

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Non-clinical studies are performed to demonstrate the health or environmental safety of new biological substances.

Non-clinical studies must be conducted in compliance with the principles of good laboratory practice, or GLP, as set forth in EU Directive 2004/10/EC.

Non-clinical (pharmaco-toxicological) studies must be conducted in compliance with the principles of good laboratory practice, or GLP, as set forth in EU Directive 2004/10/EC (unless otherwise justified for certain particular medical products, e.g., radio-pharmaceutical precursors for radio-labeling purposes).

In particular, non-clinical studies, both in vitro and in vivo, must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which define a set of rules and criteria for a quality system for the organizational process and the conditions for non-clinical studies.

These GLP standards reflect the Organization for Economic Co-operation and Development requirements.

Clinical trials of medicinal products in the EU must be conducted in accordance with EU and national regulations and the International Conference on Harmonization, or ICH, guidelines on good clinical practices, or GCP, as well as the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

Clinical trials of medicinal products in the EU must be conducted in accordance with EU and national regulations and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use, or ICH, guidelines on good clinical practices, or GCP, as well as the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

If the sponsor of the clinical trial is not established within the EU, it must appoint an EU entity to act as its legal representative.

The sponsor must take out a clinical trial insurance policy, and in most EU member states, the sponsor is liable to provide ‘no fault’ compensation to any study subject injured in the clinical trial.

The sponsor must take out

a clinical trial insurance policy, and in most EU member states, the sponsor is liable to provide ‘no fault’ compensation to any study subject injured in the clinical trial.

The regulatory landscape related to clinical trials in the EU has been subject to recent changes.

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The CTR notably harmonizes the assessment and supervision processes for clinical trials throughout the EU via a Clinical Trials Information System, which contains a centralized EU portal and database.

While the Clinical Trials Directive required a separate clinical trial application, or CTA, to be submitted in each member state, to both the competent national health authority and an independent ethics committee, much like the FDA and IRB respectively, the CTR introduces a centralized process and only requires the submission of a single application to all member states concerned.

While the Clinical Trials Directive required a separate clinical trial application, or CTA, to be submitted in each member state in which the clinical trial takes place, to both the competent national health authority and an independent ethics committee, much like the FDA and IRB respectively, the CTR introduces a centralized process and only requires the submission of a single application for multi-center trials.

The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each member state, leading to a single decision per member state.

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The aforementioned EU rules are generally applicable in the European Economic Area, which consists of the 27 EU member states plus Norway, Liechtenstein and Iceland.

Innovative products that target an unmet medical need and are expected to be of major public health interest may be eligible for a number of expedited development and review programs, such as the PRIority MEdicines, or PRIME, scheme, which provides incentives similar to the breakthrough therapy designation in the United States.

In March 2016, the European Medicines Agency, or EMA, launched the PRIME scheme, a voluntary scheme aimed at enhancing the EMA’s support for the development of medicines that target unmet medical needs.

It is based on increased interaction and early dialogue with companies developing promising medicines, to optimize their product development plans and speed up their evaluation to help them reach patients earlier.

Product developers that benefit from PRIME designation can expect to be eligible for accelerated assessment but this is not guaranteed.

Many benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and accelerated marketing authorization application assessment once a dossier has been submitted.

Importantly, a dedicated contact and rapporteur from the Committee for Medicinal Products for Human Use is appointed early in the PRIME scheme facilitating increased understanding of the product at EMA’s committee level.

An initial meeting initiates these relationships and includes a team of multidisciplinary experts at the EMA to provide guidance on the overall development and regulatory strategies.

Regulation of drug products and healthcare laws and regulations outside of the United States

Our product candidates may be subject in the future to laws and regulations related to drug products and health care imposed by jurisdictions outside of the United States, including the European Union, or EU, which may include, for instance, applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws and implementation of corporate compliance programs and reporting of payments or other transfers of value to healthcare professionals.

Outside of the United States, the provision of health care, including the pricing of pharmaceutical products, is subject to governmental control in many countries, and efforts to control prices and costs, including legislative action, will likely continue as countries attempt to manage healthcare expenditures.

Our product candidates may be subject in the future to laws and regulations related to drug products and health care imposed by jurisdictions outside of the United States, including the EU which may include, for instance, applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws and implementation of corporate compliance programs and reporting of payments or other transfers of value to healthcare professionals.

Outside of the United States, the provision of health care, including the pricing of

pharmaceutical products, is subject to governmental control in many countries, and efforts to control prices and costs, including legislative action, will likely continue as countries attempt to manage healthcare expenditures.

Data privacy and security laws

Numerous state, federal and foreign laws govern the collection, dissemination, use, access to, confidentiality, and security of personal information, including health-related information.

In the United States, numerous federal and state laws and regulations, including data breach notification laws, health information privacy and security laws, including the Health Insurance Portability and Accountability Act, or HIPAA, and federal and state consumer protection laws and regulations that govern the collection, use, disclosure, and protection of health-related and other personal information could apply now or in the future to our operations or the operations of our partners.

In the United States, numerous federal and state laws and regulations, including data breach notification laws, health information privacy and security laws, including the Health Insurance Portability and Accountability Act of 1996, or HIPAA, and federal and state consumer protection laws and regulations that govern the collection, use, disclosure, and protection of health-related and other personal information could apply now or in the future to our operations or the operations of our partners.

In addition, certain state and non-U.S.

laws, such as the California Consumer Privacy Act of 2018, the California Privacy Rights Act of 2020, and the General Data Protection Regulation, or GDPR, and the U.K.

laws, such as the California Consumer Privacy Act of 2018, or CCPA, the California Privacy Rights Act of 2020, or CPRA, and the General Data Protection Regulation, or GDPR, and the U.K.

GDPR, govern the privacy and security of personal information, including health-related information in certain circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

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HUMAN CAPITAL

At Praxis, we are fiercely dedicated to our mission to translate genetic insights into the development of therapies for CNS disorders characterized by neuronal imbalance.

We strive each day to innovate and adapt to deliver treatments that could potentially change the course of CNS disorders and to do so based on a culture built to attract, develop and retain a talent-dense workforce.

We are committed to developing our culture and our employees through our company core values – Trust , Ownership , Curiosity and Results .

At Praxis, we are passionate about our mission to translate genetic insights into the development of therapies for CNS disorders characterized by neuronal imbalance.

Our culture is designed to attract, develop and retain a talent-dense team that works tirelessly to deliver treatments to positively change the lives of patients with CNS disorders.

It is the strength of our culture and our work environment that allow us to attract top talent to Praxis.

As of February 3, 2023, we have 109 employees and plan to grow as we continue to realize the potential of our pipeline.

We Trust each other’s judgement, which is why we do not implement excessive policies.

As of March 1, 2024, we have 82 employees and plan to grow as we continue to realize the potential of our pipeline.

We are dedicated to developing our culture and our employees through our company core values – Trust , Ownership , Curiosity and Results .

We Trust each other’s judgement, which is why we do not have excessively prescriptive policies.

We value transparency among team members that leads to direct, clear, and timely feedback so we can all improve together.

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Discrimination is never tolerated.

Because we trust employees to have good judgment, there is a lot of freedom built into the way we operate.

As an example, we do not have prescriptive policies on vacation, sick or personal time – we encourage employees to take that time as they need it and align with their manager about their plans.

We have adapted to new working methodologies that embrace a virtual and cooperative work environment while emphasizing personal Ownership for actions and outcomes.

We want employees to own projects and stay engaged through communication, but we also make sure employees know that Praxis is not a nine-to-five culture.

We are a culture where employees have real accountability as we all work towards a greater goal.

Our headquarters is designated as a collaborative workspace where we gather in teams or as a company when practical and safe.

Being able to own projects, while expressing when you need a break, is something we value.

Allowing employees to best structure their days to their needs is one of the most important foundations we believe is necessary for having a sturdy organization.

Curiosity is at the center of innovation, and we are always asking how we can better help our patients.

We love to learn.

One day a month, we commit to what we call “Curiosity Day.” We ask our employees to step away from the computer, meetings and calls for a single day to focus solely on being curious – whether that means

catching up on professional articles or journals, diving deeper into a rare disease we do not currently support, challenging ourselves by exploring an area outside our comfort zone, perfecting a new skill, or even taking some time to safely enjoy the outdoors.

These opportunities have a positive impact on our employees, and enable them to bring the new knowledge and learnings to the work they do and increase the ability to deliver on our mission.

As we pursue objectives to achieve the ultimate Results , we challenge ourselves daily.

Through trust, ownership and curiosity, our employees are positioned to leave lasting results that reach the communities we serve.

Because we trust employees to have good judgment, freedom is built into our ways of working.

We have adopted working methodologies that embrace a virtual and collaborative work environment while emphasizing Ownership for actions and outcomes.

We are a culture where employees have real accountability as we all work towards furthering achievement of ambitious goals.

Curiosity fuels innovation, and we continually challenge ourselves to better help our patients.

Learning is a passion.

We set aside one day a month known as “Curiosity Day,” in which employees are guided to step away from their day-to-day work, meetings and calls to focus on being curious.

This could mean catching up on professional articles or journals, diving deeper into a rare disease we do not currently support, exploring an area outside our comfort zone, perfecting a new skill, or taking some time to enjoy the outdoors.

These opportunities to be curious have a positive impact, and enabling our employees to bring fresh insights and learnings to the organization.

As we pursue ambitious objectives to achieve Results , we challenge ourselves daily.

By exemplifying our values of trust, ownership and curiosity, employees are positioned to propel us forward to deliver lasting results for the communities we serve.

At the end of the day, the magic we witness when employees put their minds together is what we are most proud of as a company.

In identifying our employer value proposition, we have highlighted the following aspects of working at Praxis:

Our approach to building a robust clinical pipeline provides a platform and forum for exploration and innovation.

Our approach to build and progress a robust clinical pipeline provides a platform for exploration and innovation.

At Praxis, we are all involved in building the company together, and as a flat and agile organization, each employee has an impact.

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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