SCN8A-related epilepsy with encephalopathy

Over 3,000 referrals received to date meet pre-qualifying eligibility criteria for ulixacaltamide Phase 3 studies in the Essential3 program for essential tremor (ET); enrollment on track to be completed in 1H 2024 with topline results in 2H 2024 Topline results from the PRAX-628 study in epilepsy patients with photo-paroxysmal response (PPR) expected in 1Q 2024; preliminary analysis of 15 mg cohort exceeded expectations Tolerability and efficacy results from Part 1 of the EMBRAVE study of elsunersen were presented at the American Epilepsy Society 2023 Annual Meeting, showing 43% median reduction in seizures; received PRIME designation from the European Medicines Agency for the treatment of SCN2A gain-of-function developmental and epileptic encephalopathy (DEE) Announced licensing partnership with Tenacia Biotechnology to develop and commercialize ulixacaltamide for ET in Greater China with total potential consideration of over $275 million Completed underwritten public offering with over $160 million in net proceeds to extend cash runway into 2026 BOSTON, March 05, 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 a corporate update and reported financial results for the fourth quarter and full-year 2023. “2023 was a transformational year for Praxis. Living by our Dare for More™ motto, we made significant advancements across our portfolio of precision therapies for CNS disorders, established strategic collaborations and strengthened our financial position, which we believe will carry us beyond our upcoming milestones in the year ahead,” said Marcio Souza, president and chief executive officer of Praxis. “Notably, the strong participation we are seeing in our Essential3 Phase 3 studies in ulixacaltamide for essential tremor continues to highlight the significant unmet need for new therapies in essential tremor. We are also encouraged by the latest data supporting our highly differentiated epilepsy portfolio, including elsunersen and PRAX-628.” Mr. Souza continued, “Looking ahead, we plan to report topline results from the PRAX-628 study in the first quarter, complete enrollment in Essential3 in the first half of this year and expect topline results from the Phase 2 EMBOLD study of PRAX-562 for the treatment of pediatric patients with DEEs mid-year. Together, these advancements, through patient-guided development strategies, will further position Praxis at the forefront of precision medicine for CNS disorders.” Recent Highlights and Anticipated Milestones: Cerebrum™ Small Molecule Platform Ulixacaltamide for ET: In November 2023, Praxis initiated Essential3, the Phase 3 program for ulixacaltamide. Enrollment in Essential3 is expected to complete in the first half of 2024, with topline results expected in the second half of 2024 to support a planned New Drug Application (NDA) submission in 2025. Essential3 is comprised of two simultaneous Phase 3 studies including a 12-week, parallel design study and a 12-week randomized withdrawal study for stable responders.Essential3 incorporates learnings from the Phase 2 Essential1 study including the use of a single 60 mg dose, using a modified Activities of Daily Living scale (mADL11) as the primary endpoint based on feedback from the U.S. Food and Drug Administration (FDA), and conducting the study in a decentralized manner. In the Phase 2 Essential1 study, mADL11 produced a statistically significant and clinically meaningful response in ulixacaltamide when compared to placebo after 8 weeks of treatment (p=0.042, nominal).Essential3 has over 3,000 referrals who have met the pre-qualifying eligibility criteria from the ongoing recruitment campaign started in November 2023. PRAX-628 for Focal Epilepsy: The Phase 2a PPR study to evaluate the efficacy and safety of PRAX-628 across two cohorts, dosed at 15 mg and 45 mg, continues to advance, with plans to report topline results in the first quarter of 2024. PPR studies measure electroencephalogram (EEG) signatures after intermittent photic stimulation and are widely used as a marker of anti-seizure efficacy and to aid in dose determination.Preliminary analysis of the 15 mg cohort exceeded Praxis’ drug activity expectations and confirmed its decision to initiate a Phase 2b study of PRAX-628 in focal epilepsy in the second half of 2024.The Phase 2a study builds on positive results from the Phase 1 dose escalation study 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.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. PRAX-562 for SCN2A and SCN8A DEEs: Praxis expects topline results from the PRAX-562 Phase 2 EMBOLD study for the treatment of pediatric patients with DEEs in mid-2024. The EMBOLD study is a randomized, double-blind, placebo-controlled Phase 2 clinical study to evaluate the safety, tolerability, efficacy (motor seizure frequency) and pharmacokinetics of PRAX-562 in pediatric patients aged 2 to 18 years with DEEs, followed by an open-label extension. Up to 20 participants with SCN2A-DEE or SCN8A-DEE are expected to be enrolled. Solidus™ Antisense Oligonucleotide (ASO) Platform Elsunersen (PRAX-222) for SCN2A Gain-of-Function (GoF) Developmental Epilepsies: At the American Epilepsy Society 2023 Annual Meeting, Praxis shared data from Part 1 of the EMBRAVE study, where four patients were dosed once a month for a four-month period. Results showed a 43% median reduction in seizures from baseline, a 48% increase in seizure-free days from baseline and no drug-related treatment-emergent adverse events or serious adverse events. Elsunersen received PRIME designation from the European Medical Agency (EMA) for the treatment of SCN2A GoF DEEs. The EMA’s PRIME designation provides enhanced development support for priority medicines that target an unmet need and was granted based on the Part 1 data from the EMBRAVE study that showed a reduction in seizures and improvement in seizure free days, as well as preclinical data.Praxis is completing multiple global regulatory interactions in the first quarter of 2024 in anticipation of starting the pivotal phase of the program later this year. Corporate Update: In January 2024, Praxis completed an underwritten public offering. The net proceeds from the offering were approximately $161.7 million. As of February 29, 2024, Praxis had cash and cash equivalents of $247.6 million, which is anticipated to fund operations into 2026.In January 2024, Praxis announced a licensing partnership with Tenacia Biotechnology to develop and commercialize ulixacaltamide for the treatment of ET in Greater China, including mainland China, Hong Kong, Macau and Taiwan, with total potential consideration of over $275 million. Fourth Quarter and Full Year 2023 Financial Results: As of December 31, 2023, Praxis had $81.3 million in cash and cash equivalents, compared to $100.5 million in cash, cash equivalents and marketable securities as of December 31, 2022. This decrease of $19.2 million primarily reflects cash used in operations of $111.1 million during the year ended December 31, 2023, partially offset by $63.4 million in net proceeds from the June 2023 follow-on public offering and $28.2 million in net proceeds from at-the-market offerings. The Company’s cash and cash equivalents as of December 31, 2023, combined with $161.7 million net proceeds from the January 2024 follow-on offering and $5.3 million from January 2024 at-the-market offerings, are expected to fund operations into 2026. Praxis recognized $0.5 million and $2.4 million in collaboration revenue during the three months and year ended December 31, 2023, respectively, related to its Option and License Agreement with UCB which was entered into in December 2022. Research and development expenses were $18.4 million for the fourth quarter of 2023, compared to $28.3 million for the fourth quarter of 2022. Research and development expenses were $86.8 million for the year ended December 31, 2023, compared to $155.0 million for the year ended December 31, 2022. The decrease in research and development expenses for full year 2023 of $68.2 million was primarily attributable to $61.4 million in decreased expenses related to the Company’s Cerebrum™ platform. General and administrative expenses were $9.9 million for the fourth quarter of 2023, compared to $13.1 million for the fourth quarter of 2022. General and administrative expenses were $42.1 million for the year ended December 31, 2023, compared to $59.9 million for the year ended December 31, 2022. The decrease in general and administrative expenses for full year 2023 of $17.8 million was primarily attributable to a decrease of $7.6 million in professional fees and consulting expenses, $7.4 million in personnel-related expenses due to a decrease in headcount, and $2.9 million in other general and administrative expenses. Praxis incurred a net loss of $26.9 million for the fourth quarter of 2023, including $5.7 million of stock-based compensation expense, compared to $41.2 million for the fourth quarter of 2022, including $6.4 million of stock-based compensation expense. Praxis reported a net loss of $123.3 million for the year ended December 31, 2023, including $24.9 million of stock-based compensation expense, compared to a net loss of $214.0 million for the year ended December 31, 2022, including $28.6 million of stock-based compensation expense. As of December 31, 2023, Praxis had 8.8 million shares of common stock outstanding. 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 late-stage 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. and RogCon, Inc. To learn more about the EMBRAVE study, please visit https://www.embravestudy.com/. 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 Praxis  Praxis 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, the development of our product candidates, the anticipated timing of regulatory submissions and interactions 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; 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, 2023 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.CONDENSED CONSOLIDATED BALANCE SHEETS(Amounts in thousands) (Unaudited) December 31, 2023 December 31, 2022Assets Cash and cash equivalents$81,300 $61,615 Marketable securities — 38,874 Prepaid expenses and other current assets 3,580 10,351 Property and equipment, net 588 971 Operating lease right-of-use assets 2,064 2,901 Other non-current assets 416 416 Total assets$87,948 $115,128 Liabilities and stockholders’ equity Accounts payable$5,815 $14,672 Accrued expenses 7,416 15,850 Operating lease liabilities 2,495 3,500 Deferred revenue 2,553 5,000 Common stock 13 5 Additional paid-in capital 723,577 606,918 Accumulated other comprehensive loss — (173)Accumulated deficit (653,921) (530,644)Total liabilities and stockholders' equity$87,948 $115,128 PRAXIS PRECISION MEDICINES, INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Amounts in thousands, except share and per share amounts) (Unaudited) Three Months EndedDecember 31, Year Ended December 31, 2023 2022 2023 2022 Collaboration revenue$515 $— $2,447 $— Operating expenses: Research and development 18,388 28,329 86,766 155,040 General and administrative 9,933 13,124 42,054 59,946 Total operating expenses 28,321 41,453 128,820 214,986 Loss from operations (27,806) (41,453) (126,373) (214,986)Other income: Other income, net 928 280 3,096 957 Total other income 928 280 3,096 957 Net loss$(26,878) $(41,173) $(123,277) $(214,029)Net loss per share attributable to common stockholders, basic and diluted$(2.97) $(12.98) $(18.69) $(69.65)Weighted average common shares outstanding, basic and diluted 9,060,813 3,172,981 6,594,316 3,073,100

XEN1101 Phase 3 epilepsy program continues to progress with X-TOLE2 and X-TOLE3 in focal onset seizures and X-ACKT in primary generalized tonic-clonic seizures; completion of patient enrollment in X-TOLE2 expected in late 2024 to early 2025 Planned “end-of-Phase 2” meeting with the FDA in April to support the initiation of XEN1101 Phase 3 program in major depressive disorder in the second half of the year Strong financial position with approximately $930 million to fully support XEN1101 Phase 3 programs in epilepsy and major depressive disorder and expected cash runway into 2027 Conference call at 4:30 pm ET today VANCOUVER, British Columbia, Feb. 29, 2024 (GLOBE NEWSWIRE) -- Xenon Pharmaceuticals Inc. (Nasdaq:XENE), a neurology-focused biopharmaceutical company, today reported financial results for the fourth quarter and full year ended December 31, 2023 and provided a corporate update. Mr. Ian Mortimer, Xenon’s President and Chief Executive Officer, stated, “I am proud of the progress made across our pipeline in 2023, culminating in the release of topline data from our XEN1101 Phase 2 proof-of-concept X-NOVA clinical trial, which demonstrated clinically meaningful drug activity in depression. We are advancing XEN1101 in major depressive disorder with plans to conduct an end-of-Phase 2 meeting with the FDA in April, and we expect to initiate our Phase 3 program in the second half of this year. We also continue to evaluate other neurological indications that present a potential fit for XEN1101’s novel mechanism and product profile. Importantly, we believe the Kv7 mechanism of XEN1101 may have broad applicability, which supports our comprehensive strategy to pursue multiple streams of late-stage clinical development in epilepsy and depression.” Mr. Mortimer added, “We continue to make progress in our broad Phase 3 epilepsy programs, and we expect patient enrollment in X-TOLE2 to be completed in late 2024 to early 2025. We remain focused on executing our clinical development plans in epilepsy and are encouraged by the enthusiasm for XEN1101 from clinical investigators and the broader neurology community.” “We have also made significant advancements across our pre-clinical pipeline, leveraging our expertise in ion channel drug discovery to identify new product candidates across various targets including pain and seizure disorders. With a strong balance sheet to support our ambitious plans, we are looking forward to advancing and growing our broad pipeline, with the goal of improving outcomes for patients in areas of high unmet medical need.” Highlights and Anticipated Milestones XEN1101 XEN1101 is a novel, potent Kv7 potassium channel opener being developed for the treatment of epilepsy, major depressive disorder, or MDD, and potentially other neurological disorders. XEN1101 for Epilepsy (Focal Onset Seizures) Xenon’s XEN1101 Phase 3 epilepsy program includes two identical Phase 3 clinical trials, called X-TOLE2 and X-TOLE3, that are designed closely after the Phase 2b X-TOLE clinical trial. These multicenter, randomized, double-blind, placebo-controlled trials are evaluating the clinical efficacy, safety, and tolerability of 15 mg or 25 mg of XEN1101 administered with food as adjunctive treatment in approximately 360 patients per study with focal onset seizures, or FOS. Xenon anticipates patient enrollment in X-TOLE2 will be completed in late 2024 to early 2025. XEN1101 for Epilepsy (Primary Generalized Tonic-Clonic Seizures) Xenon’s Phase 3 X-ACKT clinical trial is intended to support potential regulatory submissions in an additional epilepsy indication of primary generalized tonic-clonic seizures, or PGTCS. This multicenter, randomized, double-blind, placebo-controlled trial is evaluating the clinical efficacy, safety, and tolerability of 25 mg of XEN1101 administered with food as adjunctive treatment in approximately 160 patients with PGTCS. XEN1101 for Epilepsy (Open-Label Extension) Upon completion of the double-blind period in X-TOLE2, X-TOLE3, or X-ACKT, eligible patients may enter an open-label extension, or OLE, study for up to three years. In addition, the ongoing X-TOLE Phase 2b OLE has been extended from five to seven years and continues to generate important long-term data for XEN1101. XEN1101 for Major Depressive Disorder In November 2023, Xenon reported topline results from the Phase 2 proof-of-concept X-NOVA clinical trial, which evaluated the clinical efficacy, safety, and tolerability of 10 mg and 20 mg of XEN1101 in 168 patients with moderate to severe MDD. Xenon anticipates participating in an “end-of-Phase 2” meeting with the U.S. Food and Drug Administration in April to support the initiation of its late-stage XEN1101 clinical program in MDD, which will include three Phase 3 clinical trials, with the first Phase 3 study expected to initiate in the second half of 2024. Xenon is also evaluating other potential indications for the future development of XEN1101. In addition, Xenon is collaborating with the Icahn School of Medicine at Mount Sinai to support an ongoing investigator-sponsored Phase 2 proof-of-concept, randomized, parallel-arm, placebo-controlled multi-site study of XEN1101 for the treatment of MDD in approximately 60 subjects. Other Pipeline Opportunities Xenon continues to leverage its extensive ion channel expertise and drug discovery capabilities to identify validated drug targets and develop new product candidates. The near-term focus is on development candidates targeting Kv7, Nav1.1 and Nav1.7, and Xenon expects multiple candidates will enter IND-enabling studies in 2024 and 2025. Partnered Program: NBI-921352 Xenon has an ongoing collaboration with Neurocrine Biosciences to develop treatments for epilepsy. Neurocrine Biosciences has an exclusive license to XEN901, now known as NBI-921352, a selective Nav1.6 sodium channel inhibitor. A Phase 2 clinical trial is ongoing evaluating NBI-921352 in patients aged between 2 and 21 years with SCN8A developmental and epileptic encephalopathy. Fourth Quarter and Full Year Financial Results Cash and cash equivalents and marketable securities were $930.9 million as of December 31, 2023, compared to $720.8 million as of December 31, 2022. The increase was primarily the result of the completion of the Company’s public equity offering in December 2023. Based on current operating plans, including the completion of the XEN1101 Phase 3 epilepsy studies and fully supporting late-stage clinical development of XEN1101 in MDD, Xenon anticipates having sufficient cash to fund operations into 2027. As of December 31, 2023, there were 75,370,977 common shares and 2,173,081 pre-funded warrants outstanding. Research and development expenses were $41.1 million for the fourth quarter of 2023, and $167.5 million for the year ended 2023, compared to $34.8 million and $105.8 million for the same periods in 2022, respectively. The increase in research and development expenses for the year was primarily attributable to expenses related to Xenon's enrollment of the XEN1101 Phase 3 epilepsy clinical trials, manufacturing to support current and future clinical trials and a potential NDA submission, the completion of the X-NOVA Phase 2 MDD clinical trial, personnel-related costs due to an increase in employee headcount, and higher stock-based compensation expense. These increases were partially offset by a decrease in expenses for the XEN496 program as a result of Xenon's decision in early 2023 to no longer pursue the clinical development of XEN496. General and administrative expenses were $12.6 million for the fourth quarter of 2023, and $46.5 million for the year ended 2023, compared to $8.5 million and $32.8 million for the same periods in 2022, 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 $8.7 million for the fourth quarter of 2023, and $31.4 million for the year ended 2023, compared to $7.1 million and $3.9 million for the same periods in 2022. The increase in other income for the year was primarily attributable to higher interest income and an unrealized fair value gain on trading securities recognized in 2023 compared to an unrealized fair value loss for the same period in 2022. Net loss was $44.7 million for the fourth quarter of 2023, and $182.4 million for the year ended 2023, compared to $37.4 million and $125.4 million for the same periods in 2022, respectively. The increase in net loss for the year was primarily attributable to higher research and development expenses driven by the ongoing XEN1101 Phase 3 epilepsy clinical trials, and 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 2023 results. The audio webcast can be accessed on the Investors section of the Xenon website. Participants can access the live conference call by dialing (800) 715-9871, or (646) 307-1963 for international callers, and provide conference ID number 9376408. A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month. About Xenon Pharmaceuticals Inc. Xenon Pharmaceuticals (Nasdaq:XENE) is a neuroscience-focused biopharmaceutical company committed to discovering, developing, and commercializing innovative therapeutics to improve the lives of people living with neurological and psychiatric disorders. We are advancing a novel product pipeline to address areas of high unmet medical need, including epilepsy and depression. 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 XEN1101 and other pipeline and development programs; the timing and results of our interactions with regulators; our ability to successfully develop and obtain regulatory approval of XEN1101 and our other product candidates; anticipated enrollment in our clinical trials of XEN1101 and the timing thereof; and our expectation that we will have sufficient cash to fund operations into 2027. 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 XEN1101, 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 of clinical trials; 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 pandemics, epidemics and other public health crises on our research and clinical development plans and timelines and results of operations, including impact on our clinical trial sites, collaborators, regulatory agencies and related review times, and contractors who act for or on our behalf; 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 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. XENON PHARMACEUTICALS INC. Condensed Consolidated Balance Sheets (Expressed in thousands of U.S. dollars) December 31, December 31, 2023 2022 Assets Current assets: Cash and cash equivalents and marketable securities $638,082 $592,087 Other current assets 6,880 8,211 Marketable securities, long-term 292,792 128,682 Other long-term assets 27,044 25,166 Total assets $964,798 $754,146 Liabilities Current liabilities: Accounts payable and accrued expenses $25,974 $22,214 Other current liabilities 1,299 488 Other long-term liabilities 9,604 9,947 Total liabilities $36,877 $32,649 Shareholders’ equity $927,921 $721,497 Total liabilities and shareholders’ equity $964,798 $754,146 XENON PHARMACEUTICALS INC. Condensed Consolidated Statements of Operations and Comprehensive Loss (Expressed in thousands of U.S. dollars except share and per share amounts) Three Months EndedDecember 31, Year EndedDecember 31, 2023 2022 2023 2022 Revenue $— $— $— $9,434 Operating expenses: Research and development 41,076 34,830 167,512 105,767 General and administrative 12,619 8,501 46,542 32,810 53,695 43,331 214,054 138,577 Loss from operations (53,695) (43,331) (214,054) (129,143)Other income 8,747 7,075 31,369 3,888 Loss before income taxes (44,948) (36,256) (182,685) (125,255)Income tax recovery (expense) 205 (1,139) 292 (118)Net loss (44,743) (37,395) (182,393) (125,373)Net loss attributable to preferred shareholders — — — (437)Net loss attributable to common shareholders $(44,743) $(37,395) $(182,393) $(124,936) Other comprehensive income (loss): Unrealized gain (loss) on available-for-sale securities $2,876 $(45) $2,923 $(2,010)Comprehensive loss $(41,867) $(37,440) $(179,470) $(127,383) Net loss per common share: Basic and diluted $(0.64) $(0.57) $(2.73) $(2.06)Weighted-average common shares outstanding: Basic and diluted 69,968,038 65,657,784 66,889,005 60,542,142 Contacts: For Investors: Chad Fugere Vice President, Investor Relations (857) 675-7275 investors@xenon-pharma.com For Media: Jodi Regts Xenon Corporate Affairs (604) 484-3353 media@xenon-pharma.com

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.