Vormatrigine

Xenon Pharmaceuticals plans to file for US approval of its epilepsy drug candidate azetukalner (XEN1101) after a late-stage study showed the experimental therapy significantly reduced seizures in patients with hard-to-treat disease, sending company shares up about 48% on the news Monday.The biotech said it expects to submit a new drug application to the FDA in the third quarter based on results from the X-TOLE2 trial in focal onset seizures (FOS).Azetukalner is designed to open KV7 potassium channels in the central nervous system, a mechanism aimed at stabilising overactive neurons by allowing potassium ions to flow and dampening excessive electrical signalling. The compound is also being studied in Phase III trials for major depressive disorder and bipolar depression."The magnitude of effect in X-TOLE2…along with its differentiated KV7 mechanism of action and ease-of-use attributes, give us great confidence in azetukalner's potential to become a preferred medication for patients living with uncontrolled seizures," said CEO Ian Mortimer.Beating prior benchmarkThe study enrolled 380 adults with FOS whose disease remained uncontrolled despite multiple medications. Participants were randomised to receive once-daily oral azetukalner at either 25 mg or 15 mg or placebo over a 12-week period. Patients were heavily pretreated, with a median five prior antiseizure medications and more than half taking three drugs concurrently at baseline.The trial met its primary endpoint, showing a median percent reduction in monthly seizure frequency of 53.2% in the 25-mg group and 34.5% in the 15-mg group, compared to 10.4% for placebo. That translated to a placebo-adjusted reduction of 42.8% in the higher-dose arm, which is better than the earlier Phase IIb X-TOLE study, where the same dose produced a 34.6% placebo-adjusted reduction in seizure frequency.X-TOLE2 also met a key secondary endpoint, with 54.8% of patients in the 25-mg cohort achieving a ≥50% reduction in monthly FOS frequency from baseline, versus 20.8% for placebo. In the 15-mg arm, 37.6% of participants achieved the same measure.Xenon said that discontinuations due to side effects occurred in 14.5% of patients in the 25-mg arm and 4.8% in the 15-mg group, compared with 3.2% in the placebo group, while serious adverse events (AEs) were reported at rates of 5.6% in the 25-mg group, 3.2% in the 15-mg cohort, and 2.4% for placebo.Beyond expectationsJefferies analysts described the results as a "home run," noting that "the Street was not even entertaining a Phase III [placebo-adjusted] separation in the 40%s range." They added that efficacy looked "convincing on an absolute basis as well, replicating the -53% reduction from Phase IIb, an impressive feat since [Xenon's] Phase II/III studies have enrolled one of the most refractory patient populations." They noted that the AE-related dropout rates for azetukalner are well within the range of 10% to 25% seen with approved anti-seizure medications, adding "we think even $2B+ peak sales is still conservative." Meanwhile, analyst Myles Minter of William Blair said Monday's readout likely sets Xenon up well to compete against two other FOS drug developers, Praxis Precision Medicines and Rapport Therapeutics, and could also put it on a path toward an acquisition. Praxis is working on the sodium channel inhibitor and functional state modulator vormatrigine (PRAX-628); top-line results from the Phase III POWER1 study are due in the second quarter, and the company expects to complete the Phase III POWER2 trial later this year and report a headline readout in 2027. Rapport recently said it would be starting a Phase III programme in the second quarter for RAP-219, a TARPγ8-specific AMPA receptor negative allosteric modulator.

Two new drug applications (NDA) for ulixacaltamide in essential tremor (ET) and for relutrigine in SCN2A and SCN8A developmental and epileptic encephalopathies (DEEs) have been submitted to the U.S. Food and Drug Administration (FDA) Pre-launch activities for ulixacaltamide and relutrigine are underway and will accelerate through 2026 Essential3 results to be presented as an oral presentation at the American Academy of Neurology Annual Meeting Cash and investments of $926 million as of December 31, 2025 and net proceeds of $621 million from January 2026 public offering fund operations into 2028 Conference call today, February 19, 2026 at 8:00 am E.T. BOSTON, Feb. 19, 2026 (GLOBE NEWSWIRE) -- Praxis Precision Medicines , Inc. (NASDAQ: PRAX), a fully integrated, leading central nervous system (CNS) precision neuroscience biopharmaceutical company, today provided a corporate update and reported financial results for the fourth quarter and full-year 2025. “After a landmark fourth quarter, filled with a breadth of clinical and regulatory advancements across our portfolio, we started 2026 with two NDA submissions for ulixacaltamide and relutrigine. Pending their expected positive reviews, we will be positioned to transition into a commercial company,” said Marcio Souza, president and chief executive officer. “The other two programs in the clinic, vormatrigine and elsunersen, will both have topline results in the first half of 2026, keeping us on track for additional NDA submissions in the next two years. Together, these four assets have a revenue potential of over $20 billion.” Recent Highlights and Anticipated Milestones Cerebrum™ Small Molecule Platform Ulixacaltamide for Essential Tremor (ET): ET is one of the most common movement disorders, affecting approximately seven million patients in the U.S., yet it is inadequately managed and undertreated with no specific drugs developed for ET currently approved, as underscored by the interest from over 200,000 patients in the Essential3 program. Ulixacaltamide was the first investigational therapy to demonstrate positive results in a Phase 3 program in ET and was granted Breakthrough Therapy Designation by the FDA in December 2025. In October 2025, Praxis announced positive topline results from both Phase 3 studies in the ESSENTIAL3 program. Following a positive pre-NDA meeting with the FDA in December 2025, Praxis has submitted an NDA for the treatment of ET. Praxis will present several oral presentations and posters on ulixacaltamide at the upcoming American Academy of Neurology (AAN) Annual Meeting, taking place April 19 to 22, 2026 in Chicago, IL. Commercial preparations and pre-launch activities are well underway and will accelerate through 2026. Praxis is scaling its commercial organization, advancing launch readiness efforts, building inventory, and will initiate its disease awareness campaign in conjunction with the AAN meeting. Relutrigine for DEEs: Relutrigine is a sodium channel modulator designed to precisely target the hyperexcitable state of sodium-channels, with therapeutic potential across developmental epilepsies. Relutrigine has been granted Breakthrough Therapy Designation and Orphan Drug Designation by the FDA. Praxis has submitted an NDA for relutrigine for the treatment of SCN2A and SCN8A DEEs based on the strong efficacy observed in the EMBOLD registrational cohort. The results of the trial were shared at the 2025 AES meeting. Enrollment in the EMERALD study in broad DEEs is progressing well and is expected to be fully enrolled in the second half of 2026. Assuming successful initial NDA approval of relutrigine, the EMERALD study, if positive, would serve as the basis for a supplemental NDA submission in 2027. Praxis has begun preparations for the commercial launch of relutrigine, including hiring key commercial roles, building sufficient inventory for launch and preparing and executing key pre-launch activities, which are expected to accelerate throughout 2026. Vormatrigine for Focal Onset Seizures (FOS) and Generalized Epilepsy: An estimated 3.5 million people in the U.S. suffer from common epilepsies. Sodium channel therapy is the cornerstone of treatment for patients with epilepsy, yet currently approved drugs have significant safety and efficacy limitations. Vormatrigine is the most potent sodium-channel modulator ever developed for epilepsy and is designed to precisely target the hyperexcitable state of sodium-channels in adult common epilepsies. The full dataset from the RADIANT Phase 2 study were presented at the 2025 American Epilepsy Society Annual Meeting , positioning vormatrigine as a best-in-disease therapy. Study results showed its fast-acting efficacy without titration, sustained seizure reduction over longer treatment duration, seizure-freedom potential, and favorable DDI, tolerability and safety profiles with once-daily dosing. The POWER1 Phase 3 study for FOS completed enrollment and exceeded its original target; topline results are expected in the second quarter of 2026. POWER2, the second Phase 3 study for vormatrigine in FOS, is enrolling patients, with completion expected in the second half of 2026 and topline results anticipated in 2027. The POWER3 study to evaluate vormatrigine as a monotherapy is on track to commence in the first half of 2026. Solidus™ Antisense Oligonucleotide (ASO) Platform Elsunersen for early-seizure-onset SCN2A DEE: SCN2A Gain-of-function (GoF)-DEE is a rare, genetic epilepsy characterized by early-onset seizures and severe impact on development. The EMBRAVE Part A Phase 1/2 study evaluating SCN2A early seizure onset patients with a 3:1 drug to sham arm evaluating safety and seizure reduction is on track for topline results in the first half of 2026. In December 2025, Praxis shared that after a favorable meeting with the FDA there was agreement to update the EMBRAVE3 registrational trial design by removing the sham control arm. Enrollment is underway, with topline results expected in 2027. Praxis remains on track to nominate a development candidate for each of its three early stage ASO therapeutic initiatives in the first half of 2026: PRAX-080 is focused on targeting PCDH19 mosaic expression disorder PRAX-090 is designed to address SYNGAP1 loss-of-function (LoF) mutations, a leading cause of severe intellectual disability and epilepsy in DEEs. PRAX-100 targets SCN2A LoF mutations, the predominant genetic link to de novo autism spectrum disorders. Corporate Updates: In January 2026, Praxis announced updates to its board of directors, key promotions and additions to the company: Jeffrey B. Kindler and Stuart Arbuckle joined the Board of Directors. Promoted Megan Sniecinski to Chief Operating Officer and Steven Petrou, Ph.D. to President of Research & Development. Appointed Orrin Devinsky, M.D., a global epilepsy leader, as Head of Clinical Strategy. Fourth Quarter and Full Year 2025 Financial Results: As of December 31, 2025, Praxis had $926.1 million in cash, cash equivalents and marketable securities, compared to $469.5 million in cash, cash equivalents and marketable securities as of December 31, 2024. This increase of $456.6 million was primarily due to net proceeds from Praxis’ October 2025 follow-on public offering and net proceeds from at-the-market sales of common stock, partially offset by cash used in operations. The Company’s cash, cash equivalents and marketable securities as of December 31, 2025, together with $621.2 proceeds from its January 2026 follow on public offering, are expected to fund operations into 2028. Research and development expenses were $77.5 million for the fourth quarter of 2025, compared to $56.3 million for the fourth quarter of 2024. Research and development expenses were $267.1 million for the year ended December 31, 2025, compared to $152.4 million for the year ended December 31, 2024. The increase in research and development expenses for full year 2025 of $114.7 million was primarily attributable to an increase of $91.9 million in Praxis’ Cerebrum™ platform, an increase of $15.3 million in personnel related costs and an increase of $5.0 million in Praxis’ Solidus™ platform. General and administrative expenses were $19.5 million for the fourth quarter of 2025, compared to $15.1 million for the fourth quarter of 2024. General and administrative expenses were $59.1 million for the year ended December 31, 2025, compared to $56.3 million for the year ended December 31, 2024. The increase in general and administrative expenses for full year 2025 of $2.8 million was primarily attributable to an increase in professional fees. Praxis incurred a net loss of $88.9 million for the fourth quarter of 2025, including $9.9 million of stock-based compensation expense, compared to $58.7 million for the fourth quarter of 2024, including $8.6 million of stock-based compensation expense. Praxis reported a net loss of $303.3 million for the year ended December 31, 2025, including $33.9 million of stock-based compensation expense, compared to a net loss of $182.8 million for the year ended December 31, 2024, including $41.4 million of stock-based compensation expense. As of December 31, 2025, Praxis had 25.2 million shares of common stock outstanding. Conference Call Praxis will discuss fourth quarter and full year 2025 financial results and business highlights on a conference call taking place today, February 19 at 8:00 am ET, which can be accessed by visiting this registration link . The live audio webcast will also be available through the Events & Presentations page of the Investors + Media section of the Company’s website . 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 has received Breakthrough Therapy Designation from the FDA and is the most advanced program within Praxis’ Cerebrum™ small molecule platform. About Vormatrigine Vormatrigine 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 seizures and generalized epilepsy. Preclinical data demonstrates vormatrigine is differentiated from standard of care, with the potential to be best-in-class for focal epilepsy. In vitro, vormatrigine has demonstrated superior selectivity for disease-state NaV channel hyperexcitability. In vivo studies of vormatrigine have demonstrated unprecedented potency in the maximal electroshock seizure (MES) model, a highly predictive translational model for efficacy in focal epilepsy. Data from patients in the RADIANT study demonstrated a robust seizure reduction and generally safe and well tolerated profile. To learn more about the POWER1 and POWER2 studies, please visit POWER studies . About Relutrigine Relutrigine is a first-in-class small molecule in development for the treatment of developmental and epileptic encephalopathies (DEEs) as a preferential inhibitor of persistent sodium current, shown to be a key driver of seizure symptoms in severe DEEs. Relutrigine’s mechanism of precision sodium channel (NaV) modulation is consistent with superior selectivity for disease-state NaV channel hyperexcitability. In vivo studies of relutrigine have demonstrated dose-dependent inhibition of seizures up to complete control of seizure activity in SCN2A, SCN8A and other DEE mouse models. Relutrigine has been generally well-tolerated in three Phase 1 studies and has demonstrated biomarker changes indicative of NaV channel modulation. Data from cohort 1 of the Phase 2 EMBOLD study demonstrated a well-tolerated, robust, short- and long-term improvement in motor seizures in a heavily pre-treated population, alongside maintained seizure freedom in some patients with SCN2A- and SCN8A-DEE. Relutrigine has received Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation from the FDA for the treatment of SCN2A-DEE, SCN8A-DEE and Dravet syndrome; as well as Breakthrough Therapy Designation (BTD), and ODD from the European Medicines Agency for the treatment of SCN2A-DEE and SCN8A-DEE. To learn more about the EMERALD study, please visit Emerald | Resilience Studies . About Elsunersen Elsunersen 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 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 ODD and RPDD from the FDA, and ODD and PRIME designations from the European Medicines Agency for the treatment of SCN2A-DEE. The elsunersen program is ongoing under a collaboration with Ionis Pharmaceuticals, Inc., and RogCon, Inc. To learn more about the EMBRAVE3 study, please visit Embrave | Resilience Studies . About Praxis Praxis Precision Medicines is a fully integrated, leading central nervous system (CNS) precision neuroscience 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 late-stage product candidates. For more information, please visit and follow us on Facebook, LinkedIn and X/Twitter . 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 clinical trials, the development of Praxis’ product candidates and plans to initiate new clinical programs, the anticipated timing of regulatory submissions and interactions, potential market opportunity and commercial potential of Praxis’ product candidates and our projected cash runway, 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; 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, 2025 to be filed 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. PRAXIS PRECISION MEDICINES, INC. CONSOLIDATED BALANCE SHEETS (Amounts in thousands) (Unaudited) December 31, 2025 December 31, 2024 Assets Cash and cash equivalents $ 357,329 $ 215,372 Marketable securities 568,759 254,156 Prepaid expenses and other current assets 11,580 11,805 Property and equipment, net 147 230 Operating lease right-of-use assets 92 1,131 Other non-current assets — 416 Total assets $ 937,907 $ 483,110 Liabilities and stockholders’ equity Accounts payable $ 24,628 $ 12,528 Accrued expenses 35,033 23,763 Operating lease liabilities 110 1,369 Common stock 15 14 Additional paid-in capital 2,017,566 1,281,522 Accumulated other comprehensive gain 563 654 Accumulated deficit (1,140,008 ) (836,740 ) Total liabilities and stockholders' equity $ 937,907 $ 483,110 PRAXIS PRECISION MEDICINES, INC. CONSOLIDATED STATEMENTS OF OPERATIONS (Amounts in thousands, except share and per share amounts) (Unaudited) Three Months Ended December 31, Year Ended December 31, 2025 2024 2025 2024 Collaboration revenue $ — $ 7,463 $ — $ 8,553 Operating expenses: Research and development 77,506 56,288 267,115 152,413 General and administrative 19,538 15,131 59,083 56,305 Total operating expenses 97,044 71,419 326,198 208,718 Loss from operations (97,044 ) (63,956 ) (326,198 ) (200,165 ) Other income: Other income, net 8,133 5,277 22,930 17,346 Total other income 8,133 5,277 22,930 17,346 Net loss $ (88,911 ) $ (58,679 ) $ (303,268 ) $ (182,819 ) Net loss per share attributable to common stockholders, basic and diluted $ (3.50 ) $ (2.94 ) $ (13.48 ) $ (10.21 ) Weighted average common shares outstanding, basic and diluted 25,407,069 19,980,179 22,504,676 17,906,794 CONTACT: Investor Contact: Praxis Precision Medicines investors@praxismedicines.com 857-702-9452 Media Contact: Dan Ferry LifeSci Advisors Daniel@lifesciadvisors.com 617-430-7576