Kv7.2 modulators(Voltage-gated potassium channel subunit Kv7.2 modulators), Kv7.3 modulators(Potassium voltage-gated channel subfamily KQT member 3 modulators)

Therapeutic Areas

Nervous System DiseasesOther DiseasesEndocrinology and Metabolic Disease

Active Indication

Depressive Disorder, MajorEpilepsy, Tonic-ClonicSeizures+ [3]

Inactive Indication-

Originator Organization

Bausch Health Americas, Inc.

Active Organization

Xenon Pharmaceuticals, Inc.1st Order Pharmaceuticals, Inc.

Bausch Health Cos., Inc.

+ [1]

Inactive Organization-

License Organization

1st Order Pharmaceuticals, Inc.

Bausch Health Cos., Inc.

Icahn School of Medicine at Mount Sinai

+ [1]

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC23H29FN2O

InChIKeyFJNPZKZPWVVSON-UHFFFAOYSA-N

CAS Registry1009344-33-5

Clinical Trials associated with Azetukalner

NCT06922110

/ Enrolling by invitationPhase 3

A Multicenter, Open-label, Long-term, Safety, Tolerability, and Efficacy Study of Azetukalner in Major Depressive Disorder

X-NOVA-OLE is a multicenter, open-label study to evaluate the long-term safety, tolerability, and efficacy of azetukalner as a monotherapy in adult participants who successfully completed an antecedent Phase 3 study of azetukalner in Major Depressive Disorder (MDD).

Start Date18 Mar 2025

Sponsor / Collaborator

Xenon Pharmaceuticals, Inc.

NCT06775379

/ RecruitingPhase 3

A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate Azetukalner in Moderate-to-Severe Major Depressive Disorder

X-NOVA2 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adult participants diagnosed with Major Depressive Disorder (MDD)

Start Date20 Dec 2024

Sponsor / Collaborator

Xenon Pharmaceuticals, Inc.

NCT05716100

/ RecruitingPhase 3

A Randomized, Double-blind, Placebo-Controlled, Multicenter Phase 3 Study to Evaluate the Safety, Tolerability, and Efficacy of XEN1101 as Adjunctive Therapy in Focal-Onset Seizures

The X-TOLE3 Phase 3 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the clinical efficacy, safety and tolerability of XEN1101 administered as adjunctive therapy in focal-onset seizures.

Start Date09 May 2023

Sponsor / Collaborator

Xenon Pharmaceuticals, Inc.

[+1]

100 Clinical Results associated with Azetukalner

100 Translational Medicine associated with Azetukalner

100 Patents (Medical) associated with Azetukalner

140

Literatures (Medical) associated with Azetukalner

01 Jun 2025·UROLOGY

Correlation of 17-OH Progesterone Changes With Semen Parameters and Pregnancy Outcomes in Hypogonadal and Eugonadal Patients After Varicocelectomy

Article

Author: Aydos, Kaan ; Yaman, Onder ; Karaburun, Murat Can ; Aydog, Ezel ; Akpinar, Cagri ; Ibis, Muhammed Arif ; Oguz, Efe Semetey ; Unal, Selman

OBJECTIVE:

To evaluate the impact of varicocele repair on serum 17-OH progesterone (17-OHP) levels and investigate its relationship with semen parameters and pregnancy outcomes in hypogonadal and eugonadal patients. Additionally, to address the unclear association between varicocele and serum 17-OHP levels in male infertility.

METHODS:

This prospective study included 135 men who underwent microscopic subinguinal varicocelectomy. Pre-operative and post-operative (3-6 months) hormone levels, including follicle-stimulating hormone, luteinizing hormone, total testosterone (TT), and 17-OHP, and semen parameters, such as total motile sperm count (TMS) and sperm morphology, were analyzed. Patients were categorized as hypogonadal (TT <300 ng/dL) or eugonadal (TT ≥300 ng/dL). Pregnancy outcomes were recorded over a 12-month follow-up period.

RESULTS:

Significant increases in TT and 17-OHP levels were observed only in hypogonadal men, while TMS and sperm morphology improved in both groups. In hypogonadal men, changes in serum 17-OHP levels (Δ-17-OHP) positively correlated with TMS improvement (r = 0.388, P = .009). Furthermore, in hypogonadal patients, although not statistically significant, Δ-17-OHP were higher in men whose partners achieved pregnancy compared to those whose partners did not.

CONCLUSION:

Varicocele repair improves semen parameters in both hypogonadal and eugonadal men. In hypogonadal men, increases in Δ-17-OHP are linked to TMS improvements, highlighting its potential as a clinical biomarker. Further studies are warranted to validate 17-OHP as a predictor of pregnancy outcomes.

01 Jun 2025·NEUROBIOLOGY OF DISEASE

Exploring potential key genes and disease mechanisms in early-onset genetic epilepsy via integrated bioinformatics analysis

Article

Author: Efthimiopoulos, Spiros ; Boulaki, Vasiliki ; Spyrou, George Μ ; Moschonas, Nicholas K

Epilepsy is a severe common neurological disease affecting all ages. Epilepsy with onset before the age of 5 years, designated early-onset epilepsy (EOE), is of special importance. According to previous studies, genetic factors contribute significantly to the pathogenesis of EOE that remains unclear and must be explored. So, a list of 229 well-selected EOE-associated genes expressed in the brain was created for the investigation of genetic factors and molecular mechanisms involved in its pathogenesis. Enrichment analysis showed that among significant pathways were nicotine addiction, GABAergic synapse, synaptic vesicle cycle, regulation of membrane potential, cholinergic synapse, dopaminergic synapse, and morphine addiction. Performing an integrated analysis as well as protein-protein interaction network-based approaches with the use of GO, KEGG, ClueGO, cytoHubba and 3 network metrics, 12 hub genes were identified, seven of which, CDKL5, GABRA1, KCNQ2, KCNQ3, SCN1A, SCN8A and STXBP1, were identified as key genes (via Venn diagram analysis). These key genes are mostly enriched in SNARE interactions in vesicular transport, regulation of membrane potential and synaptic vesicle exocytosis. Clustering analysis of the PPI network via MCODE showed significant functional modules, indicating also other pathways such as N-Glycan biosynthesis and protein N-linked glycosylation, retrograde endocannabinoid signaling, mTOR signaling and aminoacyl-tRNA biosynthesis. Drug-gene interaction analysis identified a number of drugs as potential medications for EOE, among which the non-FDA approved drugs azetukalner (under clinical development), indiplon and ICA-105665 and the FDA approved drugs retigabine, ganaxolone and methohexital.

01 Jun 2025·BIOORGANIC CHEMISTRY

Design and synthesis of novel cyclohexanecarboxamides with anticonvulsant effect by activating Nrf2-ARE pathway

Article

Author: Korany, Reda M S ; Elbaset, Marawan A ; Abdel-Maksoud, Mohammed S ; Abd-Allah, Walaa H ; Ibrahim, Ibrahim M ; Hassan, Rasha M

This study investigated a series of novel cyclohexanecarboxamide derivatives 4a-e, 5a-e and 6a-e as anticonvulsant and neuroprotective agents. Compounds 4a-e, 5a-e, and 6a-e were synthesized starting from cyclohexanone and aniline derivatives and evaluated for their anticonvulsant effects using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models. The most potent compounds 4b, 5c, and 6d demonstrated 83.33 % protection in the scPTZ test, while compounds 5a and 6b showed 100 % protection in the MES test. Further quantitative evaluation showed that compound 6d was the most active derivative in scPTZ test (ED₅₀ = 0.04 mmol/kg) and it was more potent than the two reference drugs phenobarbital and ethosuximide by 1.7 and 25.7-fold, respectively. Notably, all the compounds were free from neurotoxic side effects. Mechanistic studies indicated that the compounds 4b, 5c, and 6d exerted neuroprotective effects by modulating oxidative stress markers and activating the Nrf2/ARE pathway. Histopathological examination of brain of animals treated with compounds 4b, 5c, or 6d corroborated the neuroprotective properties. Additionally, molecular docking study and dynamic simulations were also carried out to study the mechanism of Nrf2 activation by the most active compound 6d. These results spotlight the potential of these derivatives as promising candidates for further development as anti-epileptic and neuroprotective agents.

News (Medical) associated with Azetukalner

16 May 2025

·www.prnewswire.com

Neurocrine Biosciences to Present Wide-Ranging One-Year Data from Phase 3 CAHtalyst™ Pediatric Study at Pediatric Endocrine Society 2025 Annual Meeting

One-Year Data Show Lasting Reductions in Glucocorticoid Doses and Improvements in Clinical Outcomes with CRENESSITY™ (crinecerfont) in Pediatric Patients with Classic Congenital Adrenal Hyperplasia SAN DIEGO, May 16, 2025 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced it will present new data from the Phase 3 CAHtalyst™ Pediatric study showing lasting reductions in glucocorticoid doses in pediatric patients with classic congenital adrenal hyperplasia who received CRENESSITY™ (crinecerfont) for up to one year. In addition, the study showed that for patients on CRENESSITY, adrenocorticotropic hormone, 17-hydroxyprogesterone and androstenedione remained below baseline levels, despite substantially decreased glucocorticoid doses. Results also showed improvements in clinical outcomes, including body mass index and insulin resistance. These data will be presented at the Pediatric Endocrine Society (PES) 2025 Annual Meeting taking place from May 15-18, 2025, in National Harbor, MD. "These results demonstrate that CRENESSITY has the potential to transform the treatment landscape for children and adolescents living with classic congenital adrenal hyperplasia," said Eiry W. Roberts, M.D., Chief Medical Officer, Neurocrine Biosciences. "By simultaneously addressing the underlying hormonal imbalances and allowing for a reduction in glucocorticoid doses, we're seeing improvements in clinical outcomes, including reductions in body mass index and insulin resistance." The Phase 3 CAHtalyst Pediatric study was part of the largest-ever interventional clinical trial program in classic congenital adrenal hyperplasia (CAH) including 103 pediatric patients, four to 17 years of age. The trial consisted of a 28-week, double-blind, placebo-controlled (DBPC) period, during which patients with classic CAH on supraphysiologic glucocorticoid (GC) doses were randomized 2:1 to receive CRENESSITY or placebo, and a 24-week, open-label (OL) period, during which all patients received CRENESSITY. During both the DBPC and OL periods, GC doses were kept stable for the first four weeks and then decreased as tolerated toward more physiologic levels while maintaining or improving androstenedione (A4) relative to Day 1 baseline. Three separate analyses examined the effect of CRENESSITY on: Changes in serum A4 levels and GC doses. Changes in adrenocorticotropic hormone (ACTH) and 17-hydroxyprogesterone (17-OHP) levels. Clinical outcomes. Long-term, sustained reductions in high GC doses, in addition to improvements in key clinical outcomes, were observed in pediatric patients with up to one year of treatment with CRENESSITY: Reductions in supraphysiologic GC doses observed with 28 weeks of treatment with CRENESSITY were maintained during long-term treatment of up to one year. Importantly, for patients who were randomized to CRENESSITY during the DBPC period, the proportion who achieved a GC dose within the physiologic range (i.e., ≤11 mg/m2/d hydrocortisone equivalents) was stable from Week 28 (30%) to Week 52 (32%). Pre-glucocorticoid ACTH, 17-OHP and A4 levels were reduced to below Day 1 baseline levels in children and adolescents with classic CAH taking CRENESSITY for up to one year, even after significant reductions in GC dose. Improvements were observed in body mass index (BMI) and insulin resistance in children and adolescents with classic CAH taking CRENESSITY for up to one year. In addition, hirsutism in female participants did not worsen, despite significant reductions in GC dose. CRENESSITY was generally well tolerated, with no adrenal crises reported in the DBPC period. The most common adverse reactions with CRENESSITY were headache (25% versus 6% for placebo), abdominal pain (13% versus 0%), fatigue (7% versus 0%), nasal congestion (7% versus 3%) and epistaxis (4% versus 0%). GC Dosing Regimens in the Phase 3 CAHtalyst™ Adult and CAHtalyst Pediatric Studies Additional data will be presented regarding changes in GC regimens in both adult and pediatric patients with classic CAH. Hydrocortisone dosing frequency was more likely to decrease with CRENESSITY, as was switching to dexamethasone- and prednisolone-free regimens. These changes may reduce both the CAH treatment burden and the risk of adverse effects of chronic treatment with high-dose GCs. Additional poster pr esentations at the PES 2025 Annual Meeting include: Treatment Patterns and Changes in Health States in Pediatric Patients with Classic Congenital Adrenal Hyperplasia: An Analysis of Data from the CAHtalog™ Registry Crinecerfont Enables Reduction of Glucocorticoid Doses While Maintaining or Improving Androstenedione in Pediatric Patients with Classic Congenital Adrenal Hyperplasia: Subgroup Analyses from the CAHtalyst™ Pediatric Phase 3 Study Crinecerfont Allows for More Physiologic Glucocorticoid Treatment with Greater Reductions of Androstenedione in Pediatric Patients with Classic Congenital Adrenal Hyperplasia: Analyses of Individual Patient Data from the CAHtalyst™ Pediatric Study About Congenital Adrenal Hyperplasia Congenital adrenal hyperplasia (CAH) is a rare genetic condition that results in an enzyme deficiency that alters the production of adrenal steroid hormones, such as cortisol, aldosterone and adrenal androgens, which are essential for life. Approximately 95% of CAH cases are caused by variants of the CYP21A2 gene that leads to deficiency of the enzyme 21-hydroxylase. Severe deficiency of this enzyme leads to an inability of the adrenal glands to produce enough cortisol and, in approximately 75% of cases, aldosterone. Because individuals with CAH are still able to produce androgens, the unused precursors that would normally be used to make cortisol instead result in the production of excess amounts of androgens. If left untreated, CAH can result in salt wasting, dehydration and even death. Historically, exogenous glucocorticoids (GCs) have been used to correct the endogenous cortisol deficiency, but doses higher than those for cortisol replacement (supraphysiologic) are needed to lower the elevated levels of adrenocorticotropic hormone (ACTH) and adrenal androgens. However, GC treatment at high doses has been associated with serious and significant complications of steroid excess, including metabolic issues such as weight gain and diabetes, cardiovascular disease and osteoporosis. Additionally, long-term treatment with high-dose GCs may have psychological and cognitive impacts, such as changes in mood and memory. Adrenal androgen excess has been associated with abnormal bone growth and development in pediatric patients, female health problems such as excess facial hair growth and menstrual irregularities, in addition to fertility issues in both sexes. The symptoms of high ACTH may include testicular adrenal rest tumors (TARTs) or ovarian adrenal rest tumors (OARTs). About The CAHtalyst™ Pediatric Study The Phase 3 CAHtalyst global registrational studies were designed to evaluate the safety, efficacy and tolerability of CRENESSITY in children and adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The CAHtalyst studies were the largest-ever interventional clinical trial program in classic CAH, including 285 pediatric and adult patients. The CAHtalyst Pediatric study included 103 pediatric patients four to 17 years of age. The study tested two questions. The first question evaluated whether four weeks of CRENESSITY treatment could improve androgen control. The second question evaluated whether an additional 24 weeks of CRENESSITY treatment enabled customized glucocorticoid (GC) down-titration while androstenedione levels were maintained or improved. Data from the CAHtalyst Phase 3 studies supported approval of CRENESSITY by the U.S. Food and Drug Administration in December 2024. The open-label extension treatment portions of both studies are ongoing. About CRENESSITY™ (crinecerfont) CRENESSITY is a potent and selective, oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist developed to reduce and control excess adrenocorticotropic hormone (ACTH) and adrenal androgens through a non-glucocorticoid (GC) mechanism for the treatment of classic congenital adrenal hyperplasia (CAH). Antagonism of CRF1 receptors in the pituitary has been shown to decrease ACTH levels, which in turn decreases the production of adrenal androgens and potentially the symptoms associated with CAH. The robust clinical study data demonstrate that lowering adrenal androgen levels with CRENESSITY enables lower, more physiologic dosing of GCs to replace missing cortisol. CRENESSITY comes in capsules and an oral solution. The capsule formulation is available in 50 mg and 100 mg doses. The oral solution is available as a 50 mg/mL strength formulation. For adults 18 years of age and older, the recommended dosage is 100 mg twice daily taken orally with a meal. For pediatric patients four to 17 years of age weighing less than 55 kg (121 lbs), the recommended dosage is based on body weight and is administered twice daily, taken orally with a meal. For pediatric patients weighing more than 55 kg (121 lbs), the recommended dosage is 100 mg twice daily taken orally with a meal. Healthcare providers can work with patients to determine the appropriate formulation for use depending on patient needs. Patients receiving CRENESSITY should continue GC therapy for cortisol replacement. Important Information Approved Uses CRENESSITY (crinecerfont) is a prescription medicine used together with glucocorticoids (steroids) to control androgen (testosterone-like hormone) levels in adults and children 4 years of age and older with classic congenital adrenal hyperplasia (CAH). IMPORTANT SAFETY INFORMATION Do not take CRENESSITY if you: Are allergic to crinecerfont, or any of the ingredients in CRENESSITY. CRENESSITY may cause serious side effects, including: Allergic Reactions. Symptoms of an allergic reaction include tightness of the throat, trouble breathing or swallowing, swelling of the lips, tongue, or face, and rash. If you have an allergic reaction to CRENESSITY, get emergency medical help right away and stop taking CRENESSITY. Risk of Sudden Adrenal Insufficiency or Adrenal Crisis With Too Little Glucocorticoid (Steroid) Medicine. Sudden adrenal insufficiency or adrenal crisis can happen in people with congenital adrenal hyperplasia who are not taking enough glucocorticoid (steroid) medicine. You should continue taking your glucocorticoid (steroid) medicine during treatment with CRENESSITY. Certain conditions such as infection, severe injury, or shock may increase your risk for sudden adrenal insufficiency or adrenal crisis. Tell your healthcare provider if you get a severe injury, infection, illness, or have planned surgery during treatment. Your healthcare provider may need to change your dose of glucocorticoid (steroid) medicine. Before taking CRENESSITY, tell your healthcare provider about all of your medical conditions, including if you are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. The most common side effects of CRENESSITY in adults include tiredness, headache, dizziness, joint pain, back pain, decreased appetite, and muscle pain. The most common side effects of CRENESSITY in children include headache, stomach pain, tiredness, nasal congestion, and nosebleeds. These are not all the possible side effects of CRENESSITY. Call your healthcare provider for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at or call 1-800-FDA-1088. Dosage Forms and Strengths: CRENESSITY is available in 50 mg and 100 mg capsules, and as an oral solution of 50 mg/mL. Please see full Prescribing Information. About Neurocrine Biosciences, Inc. Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, classic congenital adrenal hyperplasia, endometriosis* and uterine fibroids,* as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, X and Facebook. (*in collaboration with AbbVie) The NEUROCRINE BIOSCIENCES Logo, NEUROCRINE and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. CRENESSITY, CAHtalyst and CAHtalog are trademarks of Neurocrine Biosciences, Inc. Forward-Looking Statements In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements regarding the potential benefits to be derived from CRENESSITY for the treatment of classic congenital adrenal hyperplasia (CAH); the value and benefits CRENESSITY brings to patients with CAH; the ability of Neurocrine Biosciences to ensure patients have access to CRENESSITY; and whether the results from our clinical trials of CRENESSITY are indicative of real-world results. Factors that could cause actual results to differ materially from those stated or implied in the forward-looking statements include, but are not limited to, the following: risks and uncertainties associated with Neurocrine Biosciences' business and finances in general, as well as risks and uncertainties associated with the commercialization of CRENESSITY, including the extent to which patients and physicians accept and adopt CRENESSITY; whether CRENESSITY receives adequate reimbursement from third-party payors; risks and uncertainties relating to competitive products and technological changes that may limit demand for CRENESSITY; risks associated with the Company's dependence on third parties for development and manufacturing activities related to CRENESSITY, and the ability of the Company to manage these third parties; risks that additional regulatory submissions for CRENESSITY may not occur or be submitted in a timely manner; risks that the FDA or other regulatory authorities may make adverse decisions regarding CRENESSITY; risks that post-approval CRENESSITY commitments or requirements may be delayed; risks that CRENESSITY may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks and uncertainties relating to competitive products and technological changes that may limit demand for CRENESSITY; and other risks described in the Company's periodic reports filed with the Securities and Exchange Commission, including without limitation the Company's quarterly report on Form 10-Q for the quarter ended March 31, 2025. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law. © 2025 Neurocrine Biosciences, Inc. All Rights Reserved. CAP-CFT-US-0027 05/2025 SOURCE Neurocrine Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 3

12 May 2025

·investor.xenon-pharma.com

Xenon Reports First Quarter 2025 Financial Results and Provides Business Update

– Phase 3 azetukalner X-TOLE2 FOS study patient recruitment expected to complete in the next few months with topline data anticipated in early 2026 – Phase 3 azetukalner X-NOVA3 MDD and Phase 3 BPD studies on track to initiate mid-year – Results from completed Mount Sinai IST in MDD confirm azetukalner drug activity as seen in X-NOVA – Phase 1 study in healthy volunteers initiated for follow-on Kv7 channel opener XEN1120 – IND filing and Phase 1 study start for XEN1701, lead Nav1.7 candidate, anticipated in Q3 2025 – Conference call at 4:30 pm ET today VANCOUVER, British Columbia and BOSTON, May 12, 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 reported financial results for the first quarter ended March 31, 2025, and provided a business update. “We continue to make steady progress across our Phase 3 epilepsy program, with patient recruitment into our X-TOLE2 study expected to complete in the next few months, positioning us to report topline results in early 2026. While this timing represents a modest shift from our prior guidance, we are encouraged that we are nearing the end of this important study which represents a significant milestone for Xenon, getting us one step closer to a potential first commercial product launch,” said Ian Mortimer, President and Chief Executive Officer of Xenon. “Outside of epilepsy, we have made tremendous progress across our pipeline, including with azetukalner expansion into neuropsychiatry and significant advancements in our earlier-stage programs. Enrollment in our first Phase 3 MDD study, X-NOVA2, is progressing well and our second MDD study, X-NOVA3, along with our first Phase 3 study in bipolar depression are on track for initiation in the near term. In addition, there is great excitement and momentum across our early-stage programs, with the initiation of a Phase 1 study for our first follow-on Kv7 candidate, XEN1120, that we expect to study in pain, and we anticipate a regulatory filing followed by a Phase 1 study start for our lead Nav1.7 candidate, XEN1701, in the third quarter. It’s an incredibly exciting time for Xenon as we advance multiple late-stage development programs and continue to progress multiple early-stage programs, with important milestones expected across our pipeline over the coming year,” 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 early 2026. 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. Xenon presented at the American Academy of Neurology Annual Meeting (AAN), including 36-month data from the ongoing X-TOLE open-label extension (OLE) study of azetukalner in patients with FOS, which demonstrated sustained monthly reduction in seizure frequency, impressive seizure freedom rates, and a consistent AE profile suggesting long-term efficacy and tolerability of azetukalner. 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 announced plans for a Phase 3 BPD program earlier this year, with initiation of the first azetukalner clinical study in BPD I and BPD II depression expected by mid-year. The investigator-sponsored Phase 2 proof-of-concept study of azetukalner in MDD led by Icahn School of Medicine at Mount Sinai did not meet its primary neuroimaging endpoint. Compared to placebo, azetukalner demonstrated drug activity and was associated with a numerically higher improvement in MADRS and SHAPS scores across all time periods measured, consistent with results seen in Xenon’s Phase 2 X-NOVA study. Azetukalner was generally well tolerated, with a low rate of treatment discontinuations due to adverse events (AEs), one serious adverse event deemed unrelated to study drug, and an AE profile consistent with prior studies and the known mechanism. An abstract reviewing the results of this study has been submitted to the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting to be held May 27-30, 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. A Clinical Trial Application was recently accepted for XEN1120, a Kv7 channel opener, with a Phase 1 study in healthy adult participants now underway. Work remains ongoing with additional Kv7 development molecules and chemistries. Kv7 may have utility in a broad range of therapeutic indications including seizure disorders, pain, and neuropsychiatric disorders, such as MDD and BPD. IND-enabling work is underway with multiple Nav1.7 development candidates, with an IND (or equivalent) filing and Phase 1 study initiation for the Xenon’s lead candidate, XEN1701, expected in the third quarter. 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 to 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. Xenon plans to host multiple R&D webinars this summer to highlight certain early-stage pipeline programs. The first webinar will take place in June and focus on our approach to treating pain with drug candidates targeting both Nav1.7 and Kv7. Additional details to follow in the coming weeks. Partnered Program As part of Xenon’s ongoing collaboration with Neurocrine Biosciences, a Phase 1 study is underway of NBI-921355, an investigational, selective inhibitor of voltage-gated sodium channels Nav1.2 and Nav1.6 in development for the potential treatment of certain types of epilepsy. First Quarter Financial Results Cash and cash equivalents and marketable securities were $691.1 million as of March 31, 2025, compared to $754.4 million as of December 31, 2024. 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 March 31, 2025, there were 76,586,359 common shares and 2,173,081 pre-funded warrants outstanding. Revenue of $7.5 million was recognized for the quarter ended March 31, 2025, compared to nil for the same period in 2024. The increase was due to a milestone payment recognized in connection with the Neurocrine collaboration. Research and development expenses for the quarter ended March 31, 2025 were $61.2 million, compared to $44.3 million for the same period in 2024. The increase of $17.0 million was primarily attributable to continued enrollment in the azetukalner Phase 3 epilepsy clinical trials and Phase 3 X-NOVA2 clinical trial in MDD, increased personnel-related costs due to an increase in employee headcount, and pre-clinical and discovery programs to advance multiple potential drug candidates targeting Kv7, Nav1.7, and Nav1.1. General and administrative expenses for the quarter ended March 31, 2025 were $19.0 million, compared to $14.8 million for the same period in 2024. The increase of $4.2 million was primarily attributable to personnel-related costs due to an increase in employee headcount. Other income for the quarter ended March 31, 2025 was $8.1 million, compared to $11.5 million for the same period in 2024. The decrease of $3.4 million was primarily attributable to lower interest income. Net loss for the quarter ended March 31, 2025 was $65.0 million, compared to $47.9 million for the same period in 2024. The increase in net loss was primarily attributable to higher research and development expenses driven by the azetukalner program, increased personnel-related costs across the organization, and lower 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 first quarter 2025 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 5532604. 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 XENON PHARMACEUTICALS INC. Condensed Consolidated Balance Sheets (Expressed in thousands of U.S. dollars) XENON PHARMACEUTICALS INC. Condensed Consolidated Statements of Operations and Comprehensive Loss (Expressed in thousands of U.S. dollars except share and per share amounts) Source: Xenon Pharmaceuticals Inc.

Phase 1Phase 2Clinical ResultFinancial StatementPhase 3

04 Apr 2025

·investor.xenon-pharma.com

Xenon to Showcase Long-Term 36-Month Azetukalner Data at AAN 2025

Three epilepsy posters to be presented in scientific sessions at the American Academy of Neurology meeting Long-term 36-month data from the ongoing X-TOLE OLE study of azetukalner in focal onset seizures (FOS) Exploratory analysis of efficacy of azetukalner in FOS seizure sub-types Patient survey findings on mental health and comorbidity burdens of FOS VANCOUVER, British Columbia and BOSTON, April 04, 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 announced multiple presentations at the upcoming American Academy of Neurology Annual Meeting (AAN 2025), taking place April 5-9, 2025 in San Diego, CA. Three posters will be presented, including long-term data from the ongoing X-TOLE open-label extension (OLE) study of azetukalner in patients with focal onset seizures (FOS). The Company will also present an exploratory efficacy analysis of FOS seizure subtypes from the X-TOLE study, as well as patient survey findings about the mental health and comorbidity burdens of FOS. “Building upon more than 700+ patient-years of data to date, we are excited to share our 36-month azetukalner data from our ongoing X-TOLE open-label extension study in FOS showing sustained monthly reduction in seizure frequency, impressive seizure freedom rates, and a consistent AE safety profile suggesting long-term efficacy and tolerability of azetukalner,” stated Dr. Christopher Kenney, Chief Medical Officer of Xenon. “We are also presenting an exploratory analysis from our X‑TOLE study showing reduced seizure frequency rate across four focal seizure subtypes. These promising data sets support our conviction that azetukalner may offer hope for people who continue to seek new efficacious and well-tolerated therapies to address the debilitating impacts of uncontrolled seizures.” Poster 9‑001: Long-term Safety and Efficacy of Azetukalner, a Novel, Potent Kv7 Potassium Channel Opener in Adults With Focal Epilepsy: Update From the Ongoing 7-year Open-Label Extension of X-TOLE Presenter: Jacqueline A. French, MD, New York University Grossman School of Medicine and NYU Langone Health Session: P8: Epilepsy/Clinical Neurophysiology (EEG): Anti-seizure Medications: Clinical Trials Date/Time: April 8 from 8:00 am – 9:00 am PT Poster 9-012: Efficacy of Azetukalner in Focal Onset Seizure (FOS) Subtypes: Results From the Double‑Blind, Placebo‑Controlled X‑TOLE Study Presenter: Constanza Luzon Rosenblut, MD, Xenon Pharmaceuticals Session: P8: Epilepsy/Clinical Neurophysiology (EEG): Anti-seizure Medications: Clinical Trials Date/Time: April 8 from 8:00 am – 9:00 am PT Poster 9‑001: Is the Mental Health Burden of Epilepsy Under-Recognized in Patients Reporting Focal Onset Seizures? A Patient-Reported Outcomes Study Presenter: Joanne M. Wagner, PhD, Xenon Pharmaceuticals Session: P6: Epilepsy/Clinical Neurophysiology (EEG): Health Care Utilization and Disparities in Epilepsy Date/Time: April 7 from 11:45 am – 12:45 pm PT Exhibit Hall Xenon is hosting booth #1110 in the Exhibit Hall, which is scheduled to open at 11:30 am PT on Saturday, April 6 and close on Wednesday, April 9 at 4:00 pm PT. 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; and our ability to successfully develop and obtain regulatory approval of azetukalner and our other product candidates. 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 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; 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.

100 Deals associated with Azetukalner

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Major	Phase 3	United States	Xenon Pharmaceuticals, Inc.	20 Dec 2024
Epilepsy, Tonic-Clonic	Phase 3	United States	Xenon Pharmaceuticals, Inc.	14 Feb 2023
Epilepsy, Tonic-Clonic	Phase 3	Argentina	Xenon Pharmaceuticals, Inc.	14 Feb 2023
Epilepsy, Tonic-Clonic	Phase 3	Australia	Xenon Pharmaceuticals, Inc.	14 Feb 2023
Epilepsy, Tonic-Clonic	Phase 3	Austria	Xenon Pharmaceuticals, Inc.	14 Feb 2023
Epilepsy, Tonic-Clonic	Phase 3	Belgium	Xenon Pharmaceuticals, Inc.	14 Feb 2023
Epilepsy, Tonic-Clonic	Phase 3	Bulgaria	Xenon Pharmaceuticals, Inc.	14 Feb 2023
Epilepsy, Tonic-Clonic	Phase 3	Canada	Xenon Pharmaceuticals, Inc.	14 Feb 2023
Epilepsy, Tonic-Clonic	Phase 3	Croatia	Xenon Pharmaceuticals, Inc.	14 Feb 2023
Epilepsy, Tonic-Clonic	Phase 3	Czechia	Xenon Pharmaceuticals, Inc.	14 Feb 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05376150 (X-NOVA, Pubmed \| JAMA Netw Open)	Phase 2	Depressive Disorder, Major	168	Azetukalner 10 mg	icmfyyfhxj(kplflhupwv) = jckmtrzzom wtuiknozyt (ejpaiqrxuu, 1.34)	Positive	27 May 2025
				Azetukalner 20 mg	npmnncfher(mlrghtginu) = fwwxqeknpw gksdmbihni (unqxuphtvp, 1.1) View more
X-TOLE (AAN2025)	Phase 2	Seizures	325	Azetukalner 25 mg	cbwzvsenkc(ubqoafafwv) = 31.6% xvcmizduhp (swkgpiekql ) View more	Positive	07 Apr 2025
				Placebo
NCT03796962 (X-TOLE, NEWS) Manual	Not Applicable	Epilepsies, Partial	182	Azetukalner	obnaygyouq(ifxqmldjvg) = zdvydruhmn tjutawhrzc (rnsnklbmto ) View more	Positive	06 Dec 2024
NCT03796962 (X-TOLE, CTgov)	Phase 2	Epilepsies, Partial \| Seizures	325	XEN1101 (25 mg XEN1101)	sseqgjvhix(bfuvaksgeh) = thfclyefdu rmkklzpfht (toxwfavwgs, kaomkqthmn - dnjfagldhz) View more	-	24 Sep 2024
				XEN1101 (20 mg XEN1101)	sseqgjvhix(bfuvaksgeh) = inhlpojfpr rmkklzpfht (toxwfavwgs, vsrqdcarlo - dawjnkwkqo) View more
ESC2024	Not Applicable	-	-	Recreational drug users	idumplvvrr(oyotjbpswk) = snhghtmfjm suwpqwpefd (verievhdog )	-	31 Aug 2024
				Non-users	idumplvvrr(oyotjbpswk) = yijpleeuyy suwpqwpefd (verievhdog )
ENDO2024	Not Applicable	Adrenal Hyperplasia, Congenital 17-OH-progesterone \| androstenedione	122	Standard treatment	vdlldkcnrq(ucgrtrewyz) = lvtxoebvcu njraesdsdx (ktmthtnnuj, 109) View more	-	01 Jun 2024
				Modified-release hydrocortisone (MRHC)	vdlldkcnrq(ucgrtrewyz) = rmavwxethh njraesdsdx (ktmthtnnuj, 2353) View more
NCT05376150 (X-NOVA, Company_Website) Manual	Phase 2	Depressive Disorder, Major	168	Azetukalner 10mg	bnnwaftxae(hxamfjlqup) = pryfhbnfbb arsrxvsdof (hgzgsfwxzy )	Positive	28 May 2024
				Azetukalner 20mg	bnnwaftxae(hxamfjlqup) = gfmhlcyswh arsrxvsdof (hgzgsfwxzy ) View more
AAN2024	Not Applicable	Epilepsies, Partial	-	XEN1101 25mg	btrfcgwqcw(nlymdbprzp) = pxwrktjdxf fshvjlcasp (peswmgzwqw )	-	09 Apr 2024
				Placebo	btrfcgwqcw(nlymdbprzp) = ckhduwkiup fshvjlcasp (peswmgzwqw )
NCT03796962 (X-TOLE, AAN2024)	Phase 2	Epilepsies, Partial	285	XEN1101 10mg QD	ugyjfwrnvs(sejnfakmgn) = -83.4% at 18 months in the OLE vs DBP baseline lvffdgycii (gjlculsgjl ) View more	Positive	09 Apr 2024
				XEN1101 20mg QD
NCT03796962 (X-TOLE, AES2023) Manual	Phase 2	Epilepsies, Partial	325	XEN1101	pasvyrnvsf(kwtocblzbc) = iqpfvkzyet tnylaebiee (bopuosbdkm )	Positive	03 Dec 2023
				Placebo	pasvyrnvsf(kwtocblzbc) = xoxbzlgxfe tnylaebiee (bopuosbdkm )

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Azetukalner

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation