Nav1.2

Funding will support five research and community projects aimed at improving the lives of children with autism PHILADELPHIA, March 24, 2025 /PRNewswire/ -- Children's Hospital of Philadelphia (CHOP) is proud to announce awards from the Eagles Autism Foundation totaling more than $1.3 million over the course of the next two years. The awards will support five cutting edge autism projects from various research labs across CHOP's research enterprise. The approved research projects span from building on current ongoing and effective programs to topics and approaches that were novel, exploratory, and innovative. The community grants were distributed to projects that proved to be evidence-based, were aligned with the Eagles Autism Foundation mission, and fulfilled an immediate need in the community. Research proposals were assessed by a team of internationally recognized researchers who were individually selected based on subject matter. Significance, investigator(s), innovation, approach, and environment were all taken into consideration when assessing each project. All research proposals were evaluated for measurable outcomes and transformational impact in the field of autism. These five projects were selected to receive funding beginning in 2025: Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at CHOP, will lead a team of researchers studying variants of the ADGRB3 gene that may be related to autism. Learning more about the gene and functional impact of these variants may lead to potential diagnostic and treatment strategies. Laura McGarry, MD, PhD, a fellow in the Division of Neurology at CHOP, and her group will investigate how impairment of inhibitory interneurons, which regulate neuronal activity in the brain, is critical to autism associated with Dravet syndrome, a neurodevelopmental disorder characterized by epilepsy in the first year of life and significant developmental delays. This will build upon years of critical work researching the role of interneurons in epilepsy associated with Dravet syndrome to uncover their roles in autism. Jerome Clatot, PhD, Director of the Epilepsy Neurogenetics Initiative (ENGIN) Ion Channel/Electrophysiology Core and a research scientist at CHOP, will study mutations in the SCN2A gene that have been previously linked to autism. The goal of the project is to increase the understanding of the SCN2A gene and its role in brain development and research a potential therapeutic target for new treatments and therapies for autism. Naiara Akizu, PhD, Assistant Professor of Pathology and Laboratory Medicine at CHOP, is leading a project to study how small effect size genetic variants in chromatin regulators contribute to polygenic neurodevelopmental disorders, or disorders that can be caused by more than one mutation. Specifically, her team will study how common small effect size variants in chromatin regulators may lead to changes in gene expression, which could increase the neurodevelopmental disease burden. Additionally, CHOP's Fostering Health Program received an Eagles Autism Foundation community grant to help children in foster care with autism spectrum disorder access services. The project will provide case management, address transportation barriers for families, and develop a resource guide for foster parents, health care providers and child welfare agencies. Since 2016, CHOP has received more than $6 million in funding from the Eagles Autism Foundation for a variety of research and community impact projects. CHOP was also one of the founding beneficiaries during the 2018 launch of the Eagles Autism Challenge, which will take place again on Saturday, May 17, 2025. Additionally, the Center for Autism Research at CHOP and the Eagles Autism Foundation lead the annual Eagles Huddle Up for Autism event to raise awareness and funds for autism support. The next Huddle Up event is taking place at Lincoln Financial Field on Sunday, March 30, 2025. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Ben Leach Children's Hospital of Philadelphia (609) 634-7906 [email protected] SOURCE Children's Hospital of Philadelphia WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Praxis Precision Medicines saw its shares plummet 40% on Friday after announcing that an independent data monitoring committee (IDMC) recommended stopping Study 1 of its Essential3 programme for ulixacaltamide (PRAX-944). The candidate, which targets T-type calcium channels to block abnormal neuronal burst firing in essential tremor, is unlikely to meet its primary efficacy endpoint, according to an interim analysis of the trial.However, Praxis says it still plans to bring both Study 1 and Study 2 of the programme to completion, with top-line results expected in the third quarter. It cited "advanced state of enrollment" and IDMC suggestions that "underlying assumptions of the statistical model might have influenced this outcome" as reasons for continuing the studies.Final dataset in Q3"We are disappointed with and surprised by the outcome of the interim analysis for Study 1," remarked CEO Marcio Souza. "Following the advice of the committee, we will explore different analysis methods for the final dataset, which is expected in the third quarter of 2025."Ulixacaltamide is the company's most advanced programme, and Praxis had anticipated a regulatory filing this year. The drug showed "meaningful improvement" in TETRAS Activities of Daily Living (ADL) measures among patients receiving propranolol, according to results from the Phase II Essential1 trial published in the journal Neurology last year.While Praxis reported on Friday that it had a solid financial position with nearly $470 million in cash, cash equivalents and marketable securities as of the end of last year, it also revealed a high cash burn rate, driven by an uptick in R&D expenses. These jumped to $56.3 million in the fourth quarter of 2024, compared to $18.4 million the same time a year earlier.Gap in near-term catalystsThe company's pipeline includes vormatrigine (PRAX-628), currently in trials for focal onset seizures and generalised epilepsy. The Phase II RADIANT study and Phase II/III POWER1 registrational study are expected to produce top-line results in mid-2025 and the second half of 2025, respectively. While showing promise in preclinical studies with "superior selectivity for disease-state NaV channel hyperexcitability," vormatrigine is still years away from potential commercialisation.Relutrigine (PRAX-562), an oral inhibitor of persistent sodium current for developmental and epileptic encephalopathies (DEEs), received its third Rare Pediatric Disease Designation from the FDA in December, this time for Dravet syndrome. The compound is currently in the mid-stage EMBOLD study for SCN2A and SCN8A DEEs, with headline results anticipated in the first half of 2026 and a regulatory filing later that year. Praxis plans to start the EMERALD study for DEEs by mid-2025.Finally, elsunersen (PRAX-222), an antisense oligonucleotide designed to decrease SCN2A gene expression, is being developed for early-seizure-onset SCN2A-DEE, and advancing with a finalised registrational trial design. The Phase III EMBRAVE3 study is expected to begin enrolling patients by mid-year.On a more positive note, Praxis said UCB exercised its option to in-license global rights for an KCNT1 small-molecule development candidate. This brings Praxis an option exercise fee and potential milestone payments totalling approximately $100 million, plus tiered royalties on net sales.

– Phase 3 topline data from azetukalner FOS epilepsy program planned for H2 2025 in support of NDA filing and potential commercial launch – First of three planned Phase 3 azetukalner MDD studies underway, with second study on track to initiate mid-year – Phase 3 azetukalner bipolar depression program planned for clinical trial initiation mid-year – Early-stage portfolio advancing with Kv7 and Nav1.7 IND filings anticipated in 2025 – Neurocrine collaboration achieves milestone with initiation of Phase 1 study of Nav1.2/Nav1.6 inhibitor – Conference call at 4:30 pm ET today VANCOUVER, British Columbia and BOSTON, Feb. 27, 2025 (GLOBE NEWSWIRE) -- Xenon Pharmaceuticals Inc. (Nasdaq: XENE), a neuroscience-focused biopharmaceutical company dedicated to discovering, developing, and delivering life-changing therapeutics for patients in need, today provided a business update and reported financial results for the fourth quarter and full year ended December 31, 2024. “We expect the next 12 to 24 months will represent a catalyst-rich period for Xenon as we continue to advance our deep pipeline of promising late- and early-stage programs across multiple neurological and neuropsychiatric indications. The anticipated readout from our Phase 3 study in focal onset seizures signifies an important inflection point and could set the stage for our first potential commercial product launch in epilepsy. In addition to building upon our growing leadership in the epilepsy community, we firmly believe that azetukalner has broad potential in neuropsychiatric indications based upon strong mechanistic and scientific rationale, and we are pleased to be enrolling patients in our Phase 3 MDD program, with plans to now initiate a registrational program studying the use of azetukalner in bipolar depression,” said Ian Mortimer, President and Chief Executive Officer of Xenon. “We also expect multiple regulatory filings in 2025 coming out of our early-stage portfolio – which includes Kv7 and Nav1.7 candidates that are progressing through IND-enabling studies – to support the initiation of first-in-human trials across multiple targets. In addition, we are pleased to confirm a promising Nav1.2/Nav1.6 sodium channel inhibitor discovered in Xenon labs has progressed into a Phase 1 study as part of our collaboration with Neurocrine Biosciences, triggering a milestone payment to us,” stated Mr. Mortimer. Business Highlights and Anticipated Milestones Azetukalner Clinical Development Azetukalner, a novel, highly potent, selective Kv7 potassium channel opener, represents the most advanced, clinically validated potassium channel modulator in late-stage clinical development for the treatment of multiple indications that include epilepsy, including focal onset seizures (FOS) and primary generalized tonic-clonic seizures (PGTCS), as well as neuropsychiatric disorders including major depressive disorder (MDD) and bipolar depression (BPD). Epilepsy Programs Phase 3 X-TOLE2/3 azetukalner clinical studies in FOS continue to advance, with the first topline data readout anticipated in the second half of 2025. Phase 3 X-ACKT clinical study continues to enroll patients and is intended to support potential regulatory submissions in an additional epilepsy indication of PGTCS. Building upon more than 700+ patient-years of data to date from the ongoing X-TOLE open-label extension (OLE) study, Xenon continues to generate long-term scientific evidence supporting azetukalner’s compelling efficacy and safety profile, with approximately one in three patients on drug for at least 36 months achieving seizure freedom for a period of one year or longer. Xenon continues to present data at leading medical conferences, including the upcoming medical congresses of the American Society for Experimental Neurotherapeutics (ASENT) and the American Academy of Neurology (AAN) taking place in the first half of this year. Neuropsychiatric Programs X-NOVA2, the first of three planned Phase 3 clinical trials evaluating azetukalner in patients with MDD is currently enrolling patients, and X-NOVA3 is expected to initiate mid-year. Xenon announces plans for a Phase 3 BPD program with initiation of the first of two azetukalner clinical studies in bipolar I and bipolar II depression expected by mid-year. Initiation of this program is based on a strong scientific rationale – supported by promising clinical data with azetukalner and the Kv7 mechanism in MDD and preclinical research examining the genetic links between BPD and Kv7 and evidence of Kv7 downregulation in BPD – as well as a large unmet medical need. Patient enrollment in the investigator-sponsored Phase 2 proof-of-concept study of azetukalner in MDD led by Icahn School of Medicine at Mount Sinai is complete, and topline results are anticipated in the first half of 2025. Early-Stage Pipeline: Next Generation Ion Channel Modulators Xenon continues to expand its portfolio by leveraging its extensive expertise to discover and develop potassium and sodium channel therapeutics, with the goal of filing multiple INDs, or equivalent, in 2025. IND-enabling work is underway with multiple Kv7 development candidates. Kv7 may have utility in a broad range of therapeutic indications including seizures, pain, and neuropsychiatric disorders, such as MDD and BPD. IND-enabling work is underway with a lead Nav1.7 development candidate. Nav1.7 is an important pain-related target, based on strong human genetic validation, that may represent a new class of medicines without the limitations of opioids. The Company expects a lead candidate within its Nav1.1 program will enter IND-enabling studies in 2025. Pre-clinical data suggests that targeting Nav1.1 could potentially address the underlying cause and symptoms of Dravet Syndrome. Partnered Program As part of Xenon’s ongoing collaboration with Neurocrine Biosciences to develop treatments for epilepsy, NBI-921355, a Nav1.2 and Nav1.6 sodium channel inhibitor in development for the potential treatment for certain types of epilepsy, has progressed into a Phase 1 clinical study in healthy adult participants, triggering an anticipated $7.5 million milestone payment to Xenon. Corporate Xenon announced that Sherry Aulin plans to step down as Chief Financial Officer due to personal reasons. Ms. Aulin is expected to continue to serve as CFO until June 30, 2025, and then act as an advisor through the end of August to ensure a smooth transition. “Sherry has made invaluable contributions to the organization over the last decade and was instrumental in helping build Xenon as we evolved from a discovery organization to what is now a late-stage clinical organization readying for our first potential drug approval and commercial launch,” said Mr. Mortimer. “On behalf of the Board and our entire Xenon team, I want to thank Sherry for her successful leadership as CFO and commitment to ensure a smooth transition at this important time for the company.” “While I am stepping down for personal reasons, I remain excited about Xenon’s future, as it enters this transformational period driving towards commercialization, as well as the significant impact Xenon’s therapeutics could potentially have on the lives of patients around the world. It has been a privilege to serve as CFO of Xenon, and I am truly honored to have worked alongside such a talented team, and very confident that Xenon is positioned for success,” said Ms. Aulin. Fourth Quarter & Full Year Financial Results Cash and cash equivalents and marketable securities were $754.4 million as of December 31, 2024, compared to $930.9 million as of December 31, 2023. Based on current operating plans, including the completion of the azetukalner Phase 3 epilepsy studies and supporting late-stage clinical development of azetukalner in MDD and BPD, Xenon anticipates having sufficient cash to fund operations into 2027. As of December 31, 2024, there were 76,416,086 common shares and 2,173,081 pre-funded warrants outstanding. Research and development expenses were $59.5 million for the fourth quarter of 2024, and $210.4 million for the year ended 2024, compared to $41.1 million and $167.5 million for the same periods in 2023, respectively. The increase in research and development expenses for the year was primarily attributable to the azetukalner program and increased expenses related to the ongoing Phase 3 epilepsy clinical trials, the initiation of the first Phase 3 MDD clinical trial, as well as manufacturing activities to support current and future clinical trials and a potential NDA submission, and increased personnel-related costs due to an increase in employee headcount and higher stock-based compensation expense. General and administrative expenses were $18.0 million for the fourth quarter of 2024, and $68.9 million for the year ended 2024, compared to $12.6 million and $46.5 million for the same periods in 2023, respectively. The increase in general and administrative expenses for the year was primarily attributable to personnel-related costs due to an increase in employee headcount and higher stock-based compensation expense, and an increase in professional and consulting fees. Other income was $7.9 million for the fourth quarter of 2024, and $40.9 million for the year ended 2024, compared to $8.7 million and $31.4 million for the same periods in 2023. The increase in other income for the year was primarily attributable to higher interest income. Net loss was $65.7 million for the fourth quarter of 2024, and $234.3 million for the year ended 2024, compared to $44.7 million and $182.4 million for the same periods in 2023, respectively. The increase in net loss for the year was primarily attributable to higher research and development expenses driven by the azetukalner program, as well as increased personnel-related costs and stock-based compensation expense across the organization, partially offset by an increase in interest income. Conference Call Information Xenon will host a conference call and webcast today at 4:30 pm Eastern Time (1:30 pm Pacific Time) to discuss its fourth quarter and full year 2024 results. A listen-only webcast can be accessed on the Investors section of the Xenon website, with a replay available following the event. Participants can access the conference call by dialing (800) 715-9871 or (646) 307-1963 for international callers and referencing conference ID 8120798. About Azetukalner Phase 3 Epilepsy Program Xenon’s Phase 3 epilepsy program includes three Phase 3 clinical trials in focal onset seizures (FOS) and primary generalized tonic-clonic seizures (PGTCS). Designed closely after the Phase 2b X-TOLE clinical trial, the Phase 3 X-TOLE clinical trials are multicenter, randomized, double-blind, placebo-controlled studies evaluating the clinical efficacy, safety, and tolerability of 15 mg or 25 mg of azetukalner administered orally with food as adjunctive treatment in approximately 360 patients with FOS per study. The primary efficacy endpoint is the median percent change (MPC) in monthly seizure frequency from baseline through the 12-week double-blind period (DBP) of azetukalner compared to placebo. X-ACKT is a multicenter, randomized, double-blind, placebo-controlled study evaluating the clinical efficacy, safety, and tolerability of 25 mg of azetukalner administered with food as adjunctive treatment in approximately 160 patients with PGTCS. The primary efficacy endpoint is the MPC in monthly PGTCS frequency from baseline through the 12-week DBP of azetukalner compared to placebo. Upon completion of the DBP in the Phase 3 epilepsy studies, eligible patients may enter an OLE study for up to three years. About Azetukalner Phase 3 MDD Program Xenon’s Phase 3 MDD program includes three multicenter, randomized, double-blind, placebo-controlled clinical trials to evaluate the clinical efficacy, safety, and tolerability of 20 mg of azetukalner administered orally with food over the 6-week double-blind period (DBP) as monotherapy treatment in approximately 450 patients with moderate-to-severe major depressive disorder (MDD) per study. The primary efficacy endpoint is the change from baseline in the HAM-D17 score at week 6 in patients who received azetukalner compared to placebo. Upon completion of the DBP, eligible patients may enter an OLE study for up to 12 months. About Xenon Pharmaceuticals Inc. Xenon Pharmaceuticals (Nasdaq: XENE) is a neuroscience-focused biopharmaceutical company dedicated to discovering, developing, and delivering life-changing therapeutics. We are advancing an ion channel product portfolio to address areas of high unmet medical need, including epilepsy and depression. Azetukalner, a novel, highly potent, selective Kv7 potassium channel opener, represents the most advanced, clinically validated potassium channel modulator in late-stage clinical development for multiple indications. For more information, please visit www.xenon-pharma.com. Safe Harbor Statement This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995 and Canadian securities laws. These forward-looking statements are not based on historical fact, and include statements regarding the timing of and potential results from clinical trials; the potential efficacy, safety profile, future development plans in current and anticipated indications, addressable market, regulatory success and commercial potential of our and our partners’ product candidates; the efficacy of our clinical trial designs; our ability to successfully develop and achieve milestones in our azetukalner and other pipeline and development programs, including the anticipated filing of INDs and NDAs; the timing and results of our interactions with regulators; our ability to successfully develop and obtain regulatory approval of azetukalner and our other product candidates; and anticipated timing of topline data readout from our clinical trials of azetukalner. These forward-looking statements are based on current assumptions that involve risks, uncertainties and other factors that may cause the actual results, events, or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: clinical trials may not demonstrate safety and efficacy of any of our or our collaborators’ product candidates; promising results from pre-clinical development activities or early clinical trial results may not be replicated in later clinical trials; our assumptions regarding our planned expenditures and sufficiency of our cash to fund operations may be incorrect; our ongoing discovery and pre-clinical efforts may not yield additional product candidates; any of our or our collaborators’ product candidates, including azetukalner, may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; we may not achieve additional milestones in our proprietary or partnered programs; regulatory agencies may impose additional requirements or delay the initiation or completion of clinical trials; the impact of market, industry, and regulatory conditions on clinical trial enrollment; the impact of competition; the impact of expanded product development and clinical activities on operating expenses; the impact of new or changing laws and regulations; the impact of unstable economic conditions in the general domestic and global economic markets; adverse conditions from geopolitical events; as well as the other risks identified in our filings with the U.S. Securities and Exchange Commission and the securities commissions in British Columbia, Alberta, and Ontario. These forward-looking statements speak only as of the date hereof and we assume no obligation to update these forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements. “Xenon” and the Xenon logo are registered trademarks or trademarks of Xenon Pharmaceuticals Inc. in various jurisdictions. All other trademarks belong to their respective owner. Contacts: For Investors: Chad Fugere Vice President, Investor Relations (857) 675-7275 investors@xenon-pharma.com For Media: Colleen Alabiso Senior Vice President, Corporate Affairs (617) 671-9238 media@xenon-pharma.com Source: Xenon Pharmaceuticals Inc.