SCN2A encephalopathy

Positive preliminary analysis of 15 mg cohort in the PRAX-628 study in epilepsy patients with Photo-Paroxysmal Response (PPR) exceeds expectations; topline results expected in 1Q 2024 after completion of 45 mg cohort Enrollment for both ulixacaltamide Phase 3 Studies in the Essential3 program on track to be completed in 1H 2024 with topline results in 2H 2024 Recently announced licensing partnership with Tenacia Biotechnology to develop and commercialize ulixacaltamide in Greater China with total consideration over $275 million BOSTON, Jan. 08, 2024 (GLOBE NEWSWIRE) -- Praxis Precision Medicines, Inc. (NASDAQ: PRAX), a clinical-stage biopharmaceutical company translating genetic insights into the development of therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance, today provided an update on its portfolio and planned key milestones in 2024: Topline results of PRAX-628 in Phase 2a PPR study in the first quarter of 2024, followed by the expected initiation of the Phase 2b study in focal epilepsy in 2024Topline results for both Phase 3 studies evaluating ulixacaltamide in essential tremor in the second half of 2024Complete regulatory interactions to advance elsunersen (PRAX-222) towards a pivotal study for the treatment of SCN2A gain-of-function (GOF) developmental epilepsiesTopline results of the Phase 2 EMBOLD study of PRAX-562 in SCN2A and SCN8A developmental epilepsies in the first half of 2024 “We are thrilled to continue building on the momentum of an exciting 2023 and start the year with four assets in the clinic, including our lead program, ulixacaltamide, and PRAX-628, which continues to show its potential as a best-in-class drug in epilepsy. The recently announced partnership with Tenacia extends ulixacaltamide’s reach to Greater China, underscoring our commitment to realize the global value of our programs,” said Marcio Souza, president and chief executive officer. PRAX-628 for Focal Epilepsy Praxis made strong progress in developing PRAX-628 for focal epilepsy, which affects over 1 million Americans. Initial data from PRAX-628 show it has a good tolerability profile, a potentially wide therapeutic index and reaching efficacious concentrations within 24 hours. (poster)Praxis is conducting a Phase 2a PPR study to evaluate the efficacy 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. This approach has been validated with several approved and new therapies.A preliminary analysis of the 15 mg cohort showed that this cohort exceeds the expectations in terms of drug activity. The full data set will be disclosed after completion of the ongoing 45 mg cohort and full analysis of the Study.In 2023, Praxis disclosed results from a Phase 1 dose escalation study of PRAX-628 in healthy volunteers: PRAX-628 was generally well-tolerated at all tested doses. Pharmacokinetic data demonstrated dose-dependent exposure supporting once-daily dosing without titration to achieve potentially therapeutically effective drug concentration levels. (press release)Further analysis of patients in the Phase 1 study using qEEG data showed a pharmacodynamic effect at all dose levels and was significantly different from placebo. (poster) Ulixacaltamide for Essential TremorEssential tremor affects up to seven million people in the United States with action tremors that impact daily living, and there are currently no drugs specifically designed for essential tremor. Enrollment in Essential3 remains on track, with plans to complete in the first half of 2024 and topline results expected in the second half of 2024, supporting a planned New Drug Application (NDA) submission in 2025.Key elements of the Essential3 registrational program are: Two simultaneous Phase 3 trials, including a 12-week, parallel design study and a 12-week randomized withdrawal study for stable responders Using the modified Activities of Daily Living 11 (mADL11) as a primary endpoint In the Phase 2 Essential1 study, mADL11 produced a consistent and meaningful response in ulixacaltamide when compared to placebo after 8 weeks of treatment (p=0.042, nominal) Using a single 60 mg dose in the Phase 3 trialsSafety database for a NDA by ICH guidelines requiring 300 patients with six-months of exposure and 100 patients with one-year of exposure On January 5, 2024, Praxis announced a partnership with Tenacia Biotechnology to develop and commercialize ulixacaltamide in Greater China (press release) Elsunersen (PRAX-222) for SCN2A Gain-of-Function Developmental EpilepsiesSCN2A developmental and epileptic encephalopathy (SCN2A-DEE) is a debilitating and fatal monogenic epilepsy disorder caused by variants in the SCN2A gene. More than 70% of early-onset SCN2A-DEE patients live with uncontrolled seizures, and approximately 75% live with severe intellectual disability with patients rarely surviving beyond their teenage years. In December 2023 at the American Epilepsy Society annual conference, Praxis shared data from Part 1 of the EMBRAVE study, where four patients were dosed once a month for a four-month period (poster) Patients showed a 43% median reduction in seizures from baselinePatients showed a 48% increase in seizure-free days from baselineThere were no drug-related treatment-emergent adverse events or serious adverse events Praxis has an upcoming meeting with the FDA to discuss next steps in developing elsunersen PRAX-562 for SCN2A and SCN8A Developmental EpilepsiesPraxis continues to progress PRAX-562 as a unique sodium channel modulator targeting developmental and epileptic encephalopathies (DEEs). Praxis expects topline results from the EMBOLD study in pediatric patients with SCN2A-DEE and SCN8A-DEE in the first half of 2024 About Ulixacaltamide Ulixacaltamide is a differentiated and highly selective small molecule inhibitor of T-type calcium channels designed to block abnormal neuronal burst firing in the Cerebello-Thalamo-Cortical (CTC) circuit correlated with tremor activity. Ulixacaltamide, the most advanced program within Praxis’ Cerebrum™ small molecule platform, is currently in development for the treatment of essential tremor. www.praxisessentialtremor.com. About PRAX-628 PRAX-628 is a next-generation, functionally selective small molecule targeting the hyperexcitable state of sodium-channels in the brain that 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 (MES) model, a highly predictive translational model for efficacy in focal epilepsy. Data from the PRAX-628-101 study demonstrated that PRAX-628 can be safely dosed in healthy subjects to greater than 15 times the predicted human equivalent of the rodent MES EC50. About Elsunersen (PRAX-222) Elsunersen (PRAX-222) is an antisense oligonucleotide (ASO) designed to selectively decrease SCN2A gene expression, directly targeting the underlying cause of early-seizure-onset SCN2A-DEE to treat seizures and other symptoms in patients with gain-of-function SCN2A mutations. In vitro studies of PRAX-222 have demonstrated reduction in both SCN2A gene expression and protein levels. In vivo, PRAX-222 has demonstrated significant, dose-dependent reduction in seizures, improvement in behavioral and locomotor activity and increased survival in SCN2A mouse models, with potential to be the first disease-modifying treatment for SCN2A-DEE. PRAX-222 has received Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPD) from the FDA, and ODD and PRIME designations from the European Medicines Agency (EMA) for the treatment of SCN2A-DEE. The PRAX-222 program is ongoing under a collaboration with Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), and RogCon, Inc. To learn more about the EMBRAVE study, please visit https://www.embravestudy.com/. About SCN2A-DEESCN2A developmental and epileptic encephalopathy (SCN2A-DEE) is a debilitating and fatal monogenic epilepsy disorder caused by a variant in the SCN2A gene. The SCN2A gene is critical in the formation of sodium channel proteins in the brain, which control the flow of sodium ions into neurons. This movement of sodium ions is a major component of generating electrical signals called action potentials, the way in which the cells communicate. SCN2A-DEE presents with a wide range of phenotypes. Early-onset SCN2A-DEE presents before three months and can lead to profound impact on patients, including drug-resistant seizures, significant cognitive impairment, movement disorders such as dystonia or ataxia and problems in other body systems such as gastrointestinal or ocular. Currently there are no approved treatments for SCN2A-DEE, and the standard-of-care typically involves a regimen of many concurrent anti-seizure medications as well as medications to manage co-morbidities. Despite these interventions, more than 70% of early-onset SCN2A-DEE patients live with uncontrolled seizures, and approximately 75% live with severe intellectual disability with patients rarely surviving beyond their teenage years. About PRAX-562 PRAX-562 is a first-in-class small molecule in development for the treatment of developmental and epileptic encephalopathy (DEE) as a preferential inhibitor of persistent sodium current, shown to be a key driver of seizure symptoms in early onset SCN2A-DEE and SCN8A-DEE. PRAX-562’s mechanism of sodium channel block is consistent with superior selectivity for disease state sodium channel (NaV) channel hyperexcitability. In vivo studies of PRAX-562 have demonstrated dose-dependent inhibition of seizures up to complete control of seizure activity in SCN2A, SCN8A and other DEE mouse models. PRAX-562 has been generally well-tolerated in three Phase 1 studies and has demonstrated biomarker changes indicative of NaV channel blocking effects. PRAX-562 has received ODD and RPD from the FDA, and ODD from the European Medicines Agency for the treatment of SCN2A-DEE and SCN8A-DEE. To learn more about the EMBOLD study, please visit https://www.emboldstudy.org/. About PraxisPraxis Precision Medicines is a clinical-stage biopharmaceutical company translating insights from genetic epilepsies into the development of therapies for CNS disorders characterized by neuronal excitation-inhibition imbalance. Praxis is applying genetic insights to the discovery and development of therapies for rare and more prevalent neurological disorders through our proprietary small molecule platform, Cerebrum™, and antisense oligonucleotide (ASO) platform, Solidus™, using our understanding of shared biological targets and circuits in the brain. Praxis has established a diversified, multimodal CNS portfolio including multiple programs across movement disorders and epilepsy, with four clinical-stage product candidates. For more information, please visit www.praxismedicines.com and follow us on Facebook, LinkedIn and Twitter/X. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including express or implied statements regarding Praxis’ future expectations, plans and prospects, including, without limitation, statements regarding the anticipated timing of our clinical trials and the development of our product candidates, as well as other statements containing the words “anticipate,” “believe,” “continue,” “could,” “endeavor,” “estimate,” “expect,” “anticipate,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “seek,” “should,” “target,” “will” or “would” and similar expressions that constitute forward-looking statements under the Private Securities Litigation Reform Act of 1995. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: uncertainties inherent in clinical trials; preliminary analyses from ongoing studies differing materially from final data from preclinical studies and completed clinical trials; the expected timing of clinical trials, data readouts and the results thereof, and submissions for regulatory approval or review by governmental authorities; regulatory approvals to conduct trials; and other risks concerning Praxis’ programs and operations as described in its Annual Report on Form 10-K for the year ended December 31, 2022, its Quarterly Reports on Form 10-Q and other filings made with the Securities and Exchange Commission. Although Praxis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on information and factors currently known by Praxis. As a result, you are cautioned not to rely on these forward-looking statements. Any forward-looking statement made in this press release speaks only as of the date on which it is made. Praxis undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future developments or otherwise.

Conference call and webcast to be held tomorrow, January 2, at 8:30am ET (5:30am PT) LA JOLLA, Calif.--(BUSINESS WIRE)-- Longboard Pharmaceuticals, Inc. (Nasdaq: LBPH), a clinical-stage biopharmaceutical company focused on developing novel, transformative medicines for neurological diseases, today announced that it will host a conference call to discuss topline data from the PACIFIC Study, a Phase 1b/2a clinical trial evaluating bexicaserin (LP352) in participants with a broad range of Developmental and Epileptic Encephalopathies (DEEs). Bexicaserin is a potentially best-in-class, oral, novel, 5-HT2C receptor superagonist with no observed impact on 5-HT2B and 5-HT2A receptor subtypes. Conference Call and Webcast Details Longboard will host a conference call tomorrow, January 2, at 8:30am ET. Stockholders and other interested parties may participate in the call by following the instructions below. The live webcast can be accessed on the Events & Presentations portion of the investor page of Longboard’s website at . A replay will be available on Longboard’s website shortly after completion of the event and will be archived for up to 30 days. Participant Webcast Link: Participant Call Link: 1. Click on the call link and complete the online registration form. 2. Upon registering you will receive the dial-in info and a unique PIN to join the call as well as an email confirmation with the details. 3. Select a method for joining the call; i. Dial-In: A dial in number and unique PIN are displayed to connect directly from your phone. ii. Call Me: Enter your phone number and click “Call Me” for an immediate callback from the system. The call will come from a U.S. number. ABOUT BEXICASERIN (LP352) Bexicaserin is an oral, centrally acting, 5-HT2C superagonist in development for the potential treatment of seizures associated with DEEs such as Lennox-Gastaut syndrome, Dravet syndrome, SCN2A-related epilepsies, CDKL5 deficiency disorder, and other epileptic disorders. Bexicaserin is designed to modulate GABA and, as a result, suppress the central hyperexcitability that is characteristic of seizures. Bexicaserin has novel chemistry and attributes, and was designed to be highly specific and selective for the 5-HT2C receptor subtype, giving it the potential to reduce seizures in patients with DEEs while overcoming the known or perceived safety limitations of available drugs in the 5-HT2 class. ABOUT THE PACIFIC STUDY The PACIFIC Study is a Phase 1b/2a double-blind, placebo-controlled clinical trial to assess the safety, tolerability, efficacy and pharmacokinetics of bexicaserin (LP352) in 52 participants between the ages of 12 and 65 years old at 34 sites across the U.S. and Australia. Following a 5-week screening period and baseline evaluations, study participants initiated a dose titration over a 15-day period and subsequently continued on the highest tolerated dose throughout the maintenance period of 60 days. Following the maintenance period, participants were then titrated down and eligible participants were given the opportunity to enroll in a 52-week open-label extension program. The primary efficacy measure is median percent change from baseline in countable motor seizure frequency over the 75-day treatment period. ABOUT LONGBOARD PHARMACEUTICALS Longboard Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on developing novel, transformative medicines for neurological diseases. Longboard is working to advance a portfolio of centrally acting product candidates designed to be highly selective for specific G protein-coupled receptors (GPCRs). Longboard’s small molecule product candidates are based on more than 20 years of GPCR research. Longboard is evaluating bexicaserin (LP352), an oral, centrally acting 5-hydroxytryptamine 2C (5-HT2C) receptor superagonist with no observed impact on 5-HT2B and 5-HT2A receptor subtypes. Bexicaserin is currently in a Phase 1b/2a clinical trial, the PACIFIC Study, evaluating participants ages 12 to 65 years old with a broad range of Developmental and Epileptic Encephalopathies (DEEs), including Dravet syndrome, Lennox-Gastaut syndrome and other DEEs. Longboard is also evaluating LP659, an oral, centrally acting, next-generation sphingosine-1-phosphate (S1P) receptor subtypes 1 and 5 modulator, which is in development for the potential treatment of rare neuroinflammatory conditions in a Phase 1 single-ascending dose (SAD) clinical trial in healthy volunteers. FORWARD-LOOKING STATEMENTS Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. In some cases, you can identify forward-looking statements by words such as “to be held”, “focused on”, “will”, “potential”, “may”, “after”, “emerging”, “opportunity”, “expected”, “designed to”, “working to”, or the negative, plural or other tenses of these words or other comparable language, and they include, without limitation, statements about the following: Longboard’s planned conference call and webcast; bexicaserin (LP352), including its potential to be best-in-class, its potential to treat seizures associated with a broad range of DEEs, and its selectivity, design, chemistry, and attributes; and Longboard’s clinical and preclinical programs and product candidates, ability to develop product candidates and deliver medicines, and focus. For such statements, Longboard claims the protection of the Private Securities Litigation Reform Act of 1995. Actual events or results may differ materially from Longboard’s expectations. Factors that could cause actual results to differ materially from those stated or implied by Longboard’s forward-looking statements include, but are not limited to, the following: topline data may not accurately reflect the complete results of a particular study or trial and remain subject to audit, and final data may differ materially from topline data; PACIFIC Study participants’ diagnoses are as of time of screening and are subject to change; risks related to Longboard’s limited operating history, financial position and need for additional capital; Longboard will need additional managerial and financial resources to advance all of its programs, and you and others may not agree with the manner Longboard allocates its resources; risks related to the development and commercialization of Longboard’s product candidates; Longboard’s product candidates are in the early phases of a lengthy research and development process, the timing, manner and outcome of research, development and regulatory review is uncertain, and Longboard’s product candidates may not advance in research or development or be approved for marketing; enrolling participants in Longboard’s ongoing and intended clinical trials is competitive and challenging; nonclinical and clinical data is voluminous and detailed, and regulatory agencies may interpret or weigh the importance of data differently and reach different conclusions than Longboard or others, request additional information, have additional recommendations or change their guidance or requirements before or after approval; results of clinical trials and other studies are subject to different interpretations and may not be predictive of future results; macroeconomic events stemming from the COVID-19 pandemic or evolving geopolitical developments such as the conflicts in Ukraine and the Middle East, including but not limited to the impact on Longboard’s clinical trials and operations, the operations of Longboard’s suppliers, partners, collaborators, and licensees, and capital markets, which in each case remains uncertain; risks related to unexpected or unfavorable new data; risks related to principal stockholders or management selling some or all of their stock; risks related to relying on licenses or collaborative arrangements; other risks related to Longboard’s dependence on third parties; competition; product liability or other litigation or disagreements with others; government and third-party payor actions, including relating to reimbursement and pricing; risks related to regulatory compliance; and risks related to Longboard’s and third parties’ intellectual property rights. Additional factors that could cause actual results to differ materially from those stated or implied by Longboard’s forward-looking statements are disclosed in Longboard’s filings with the Securities and Exchange Commission (SEC). These forward-looking statements represent Longboard’s judgment as of the time of this release. Longboard disclaims any intent or obligation to update these forward-looking statements, other than as may be required under applicable law. View source version on businesswire.com: Contacts Megan E. Knight Head of Investor Relations IR@longboardpharma.com 858.789.9283 Source: Longboard Pharmaceuticals, Inc. View this news release online at:

BOSTON, Nov. 28, 2023 (GLOBE NEWSWIRE) -- Praxis Precision Medicines, Inc. (NASDAQ: PRAX), a clinical-stage biopharmaceutical company translating genetic insights into the development of therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance, today announced that it will deliver presentations on its epilepsy programs at the following upcoming meetings in Orlando, Florida. Presentations at the American Epilepsy Society (AES) Annual Meeting, as well as related scientific and patient advocacy meetings, will cover new patient data, updates on clinical progress and new paradigms for developing epilepsy therapies. AES Annual Meeting, being held December 1-5, 2023Behind the Seizure (BTS) Scientific Exhibit, being held on December 3, 2023Partners Against Mortality in Epilepsy (PAME) Conference, being held on November 30, 2023SYNGAP1 Conference, being held on November 30, 2023The Cute Syndrome Foundation (TCSF) SCN8A Clinician, Researcher, and Family Gathering, being held on December 1, 2023 “It’s an incredibly exciting time for Praxis and our epilepsy portfolio, as we share updates from first-in-patient and Phase 2 studies for elsunersen (PRAX-222), PRAX-562 and PRAX-628,” said Marcio Souza, president and chief executive officer of Praxis. “We look forward to presenting data spanning our Solidus and Cerebrum platforms at AES and related meetings in Florida, with presentations also set to highlight novel approaches to define efficient preclinical models and sensitive biomarkers for accelerating drug development for the patient populations we are seeking to serve. Our epilepsy programs have the potential to significantly impact the lives of patients and their families, and we are grateful for the opportunity to discuss these programs with the epilepsy community at multiple important meetings this week.” Praxis at AES 2023 | Orange County Convention Center Meet us at booth #421 to learn about the largest pipeline of precision epilepsy programs Head to one of our presentations listed below or visit us at the BTS Scientific Exhibit on December 3, 08:00 a.m. - 11:00 a.m. ET EMBRAVE: A Clinical Trial of PRAX-222, a Novel Antisense Oligonucleotide, in Pediatric Participants with Early Onset SCN2A Developmental and Epileptic Encephalopathy Session Date/Time: Monday, December 4, 12:00 p.m. - 2:00 p.m. ETAbstract number: 3.198Summary: Preliminary results from Part 1 of the EMBRAVE study demonstrate elsunersen tolerability and unprecedented efficacy, highlighting its potential to be the first disease-modifying treatment in early onset SCN2A developmental and epileptic encephalopathy (SCN2A-DEE). PRAX-628 is a Next Generation, Functionally Selective Small Molecule with Potent Anti-Seizure Activity and Potential as Best-in-Class Treatment for Focal Epilepsy Session Date/Time: Monday, December 4, 12:00 p.m. - 2:00 p.m. ET; platform talk at 5:00 p.m. ET [Platform D | Epilepsy Therapies] Abstract number: 3.258Summary: Combined preclinical and clinical data demonstrate PRAX-628 is differentiated from standard of care, with the potential to be best-in-class for focal epilepsy. In vivo studies demonstrate unprecedented potent anticonvulsant activity in the maximal electroshock seizure (MES) model, a highly predictive translational model for efficacy in focal epilepsy, while first-in-human findings demonstrate that PRAX-628 is well tolerated at exposures >15x the predicted efficacious exposure from mouse MES. A Novel Method to Define an EEG Composite for the Detection of Drug Effects of Next Generation Small Molecules for Epilepsy Session Date/Time: Monday, December 4, 12:00 p.m. - 2:00 p.m. ETAbstract number: 3.455Summary: Application of machine learning methods to complex EEG data has the potential to accelerate drug development in epilepsy by revealing pharmacodynamic effects of novel agents that are clearly distinguishable from placebo. In this study, we demonstrate applicability of a quantitative EEG composite to three distinct next generation small molecules, with expected generalizability to any small molecule, independent of class/target. Translational Concordance of Preclinical Seizure Models in Focal and Generalized Epilepsies Session Date/Time: Monday, December 4, 12:00 p.m. - 2:00 p.m. ETAbstract number: 3.458Summary: This study provides novel insights into the clinical validity of commonly used preclinical seizure models across the clinical epilepsy spectrum. Using a newly developed scoring matrix to assess translational concordance and predictability, mouse MES, audiogenic and 6-Hz 32 mA emerge as three acute seizure models with greatest predictive validity and versatility for ASM drug discovery. Praxis at PAME 2023 | Rosen Centre Hotel EMBRAVE: A Clinical Trial of PRAX-222, a Novel Antisense Oligonucleotide, in Pediatric Participants with Early Onset SCN2A Developmental and Epileptic Encephalopathy Session Date/Time: Thursday, November 30, 5:00 p.m. - 6:30 p.m. ETPoster number: 32Summary: Preliminary results from Part 1 of the EMBRAVE study demonstrate elsunersen tolerability and unprecedented efficacy, highlighting its potential to be the first disease-modifying treatment in early onset SCN2A-DEE. EMBOLD: A Clinical Trial of PRAX-562 in Subjects with Developmental and Epileptic Encephalopathies Followed by an Open-Label Extension Session Date/Time: Thursday, November 30, 5:00 p.m. - 6:30 p.m. ETPoster number: 38Summary: EMBOLD is the first and only DEE trial to offer a decentralized clinical trial option, balancing clinical rigor with flexibility and convenience for participants and their families. EMBOLD will provide important findings regarding the safety, tolerability, efficacy and pharmacokinetics of PRAX-562 as a potential first- and best-in-class treatment for pediatric patients with SCN2A-DEE and SCN8A-DEE. Praxis at SYNGAP1 2023 | Embassy Suites Hotel Progress Toward the Discovery of an ASO for Therapeutic Upregulation of SYNGAP1 Session Date/Time: Thursday, November 30, 1:30 p.m. - 1:45 p.m. ET | Session 4: Therapeutic Strategies to Fix SYNGAP1Oral presentation highlighting preclinical updates from our SYNGAP1 ASO platform at the annual scientific conference hosted by the SYNGAP Research Fund Praxis at TCSF 2023 | Sheraton Orlando Lake Buena Vista Resort PRAX-562: Reflection and Direction on a Next Generation Anti-Seizure Small Molecule in Development for SCN8A-DEE Session Date/Time: Friday, December 1, 6:15 p.m. ETOral presentation highlighting clinical updates from our PRAX-562 small molecule platform at the annual clinician, researcher, and family gathering for SCN8A About elsunersen (PRAX-222)Elsunersen is an ASO designed to selectively decrease SCN2A gene expression, directly targeting the underlying cause of early-seizure-onset SCN2A-DEE to treat seizures and other symptoms in patients with gain-of-function SCN2A mutations. In vitro studies of elsunersen have demonstrated reduction in both SCN2A gene expression and protein levels. In vivo, elsunersen has demonstrated significant, dose-dependent reduction in seizures, improvement in behavioral and locomotor activity and increased survival in SCN2A mouse models, with potential to be the first disease-modifying treatment for SCN2A-DEE. Elsunersen has received Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPD) from the FDA, and ODD and Priority Medicines (PRIME) designation from the European Medicines Agency (EMA) for the treatment of SCN2A-DEE. The elsunersen program is ongoing under a collaboration with Ionis Pharmaceutics, Inc., and RogCon, Inc. About PRAX-562PRAX-562 is a first-in-class small molecule in development for the treatment of DEE as a preferential inhibitor of persistent sodium current, shown to be a key driver of seizure symptoms in early onset SCN2A-DEE and SCN8A-DEE. PRAX-562’s mechanism of sodium channel block is consistent with superior selectivity for disease state sodium channel (NaV) channel hyperexcitability. In vivo studies of PRAX-562 have demonstrated dose-dependent inhibition of seizures up to complete control of seizure activity in SCN2A, SCN8A and other DEE mouse models. PRAX-562 has been generally well-tolerated in three Phase 1 studies and has demonstrated biomarker changes indicative of NaV channel blocking effects. PRAX-562 has received ODD and RPD from the FDA, and ODD from the European Medicines Agency for the treatment of SCN2A-DEE and SCN8A-DEE. To learn more about the EMBOLD study, please visit https://www.emboldstudy.org/. About PRAX-628PRAX-628 is a next-generation, functionally selective small molecule targeting the hyperexcitable state of sodium-channels in the brain that 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 (MES) model, a highly predictive translational model for efficacy in focal epilepsy. Data from the PRAX-628-101 study demonstrated that PRAX-628 can be safely dosed in healthy subjects to greater than 15 times the predicted human equivalent of the rodent MES EC50. About SCN2A-DEESCN2A-DEE is a debilitating monogenic epilepsy disorder caused by a variant in the SCN2A gene, associated with early mortality. The SCN2A gene is critical in the formation of sodium channel proteins in the brain, which control the flow of sodium ions into neurons. This movement of sodium ions is a major component of generating electrical signals called action potentials, the way in which the cells communicate. SCN2A-DEE is characterized by a broad spectrum of phenotypes. Early-onset SCN2A-DEE presents before three months and can lead to profound impact on patients, including drug-resistant seizures, significant cognitive impairment, movement disorders such as dystonia or ataxia and problems in other body systems such as gastrointestinal or ocular. Currently there are no approved treatments for SCN2A-DEE, and the standard-of-care typically involves a regimen of many concurrent anti-seizure medications as well as medications to manage co-morbidities. Despite these interventions, more than 70% of early-onset SCN2A-DEE patients live with uncontrolled seizures, and approximately 75% live with severe intellectual disability with patients rarely surviving beyond their teenage years. About SCN8A-DEESCN8A-DEE is a rare developmental and epileptic encephalopathy caused by a variant in the SCN8A gene. The SCN8A gene is critical in the formation of sodium channel proteins in the brain, which control the follow of sodium ions into neurons. This movement of sodium ions is a major component of generating electrical signals called action potentials, the way in which the cells communicate. Patients suffer from recurrent, typically drug-resistant seizures which start as early as the first day of life. The seizures can be of multiple different types, up to dozens per day, with poor response to current treatment options. Patients with SCN8A-DEE have significant cognitive disabilities, ranging from moderate to severe; often movement disorders, such as dystonia or ataxia; and problems in other body systems such as gastrointestinal or ocular. SCN8A-DEE patients also may experience autonomic features such as increases or decreases in heart rate, abnormal breathing and cyanosis. About PraxisPraxis Precision Medicines is a clinical-stage biopharmaceutical company translating insights from genetic epilepsies into the development of therapies for CNS disorders characterized by neuronal excitation-inhibition imbalance. Praxis is applying genetic insights to the discovery and development of therapies for rare and more prevalent neurological disorders through our proprietary small molecule platform, Cerebrum™, and antisense oligonucleotide (ASO) platform, Solidus™, using our understanding of shared biological targets and circuits in the brain. Praxis has established a diversified, multimodal CNS portfolio including multiple programs across movement disorders and epilepsy, with four clinical-stage product candidates. For more information, please visit www.praxismedicines.com and follow us on Facebook, LinkedIn and Twitter/X. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including express or implied statements regarding Praxis’ future expectations, plans and prospects, including, without limitation, statements regarding the development of our product candidates, including the design of clinical trials and the treatment potential of Praxis’ product candidates, as well as other statements containing the words “anticipate,” “believe,” “continue,” “could,” “endeavor,” “estimate,” “expect,” “anticipate,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “seek,” “should,” “target,” “will” or “would” and similar expressions that constitute forward-looking statements under the Private Securities Litigation Reform Act of 1995. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: uncertainties inherent in clinical trials; reported interim data from ongoing studies and trials differing materially from final data from preclinical studies and completed clinical trials; the expected timing of clinical trials, data readouts and the results thereof, and submissions for regulatory approval or review by governmental authorities; regulatory approvals to conduct trials; Praxis’ anticipated cash runway; and other risks concerning Praxis’ programs and operations as described in its Annual Report on Form 10-K for the year ended December 31, 2022, its Quarterly Reports on Form 10-Q and other filings made with the Securities and Exchange Commission. Although Praxis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on information and factors currently known by Praxis. As a result, you are cautioned not to rely on these forward-looking statements. Any forward-looking statement made in this press release speaks only as of the date on which it is made. Praxis undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future developments or otherwise.