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XEN1101 FOR EPILEPSY

Company Presentation. ASENT 2021 (Virtual meeting of the American Society for Experimental Neurotherapeutics):  “Addressing an Unmet Medical Need in Adult Focal Epilepsy with XEN1101, a Novel KV7 Modulator.” February 22-25, 2021

Company Presentation. ASENT 2021 (Virtual meeting of the American Society for Experimental Neurotherapeutics):  “Depression and Anhedonia: Acute Preclinical Efficacy for XEN1101, a Differentiated KV7 Potassium Channel Modulator.” February 22-25, 2021

Company Presentation. ASENT 2021 (Virtual meeting of the American Society for Experimental Neurotherapeutics):  “Anticonvulsant Effects of the Differentiated KV7 Channel Potentiator XEN1101 in Combination with Commonly Used Anti-Seizure Drugs.” February 22-25, 2021

Company Presentation. ASENT 2021 (Virtual meeting of the American Society for Experimental Neurotherapeutics):  “KV7 Modulators in Epilepsy and Depression.” February 22-25, 2021

Company Poster. Virtual 2020 American Epilepsy Society (AES) Annual Meeting: “Pre-clinical In Vitro and In Vivo Comparison of the Kv7 Activator XEN1101 with Ezogabine.” December 4-8, 2020

Company Presentation. 2020 Epilepsy Pipeline Conference:  “KV7 Potassium Channel Modulators for the Treatment of Epilepsy.” (Includes overview of both XEN1101 and XEN496.) August 27, 2020

Company Presentation. Eilat XV Conference:  “New Anti-Epileptic Drugs and Devices.” (Includes overview of both XEN1101 and XEN496.) July 28, 2020 

Company Poster. 2019 American Epilepsy Society (AES) Annual Meeting: “Use of Transcranial Magnetic Stimulation Data in the Design of a Dose Ranging Finding Efficacy, Safety, Tolerability and Pharmacokinetics Study of XEN1101 in Patients with Focal Epilepsy.” December 6-10, 2019

Company Poster. 2018 American Epilepsy Society (AES) Annual Meeting: “A First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Pharmacodynamics of a Novel Small Molecule KV7.2/7.3 Positive Allosteric Modulator (XEN1101) in Healthy Subjects.” December 3, 2018

Company Poster. 2018 American Epilepsy Society (AES) Annual Meeting: “A Phase 1 Study Utilizing Transcranial Magnetic Stimulation to Assess the Pharmacodynamic Effects of a Novel Potassium Channel Opener (XEN1101) on Human Cortical Excitability.” December 3, 2018

King’s College London Presentation. 13th European Congress on Epileptology:  “A First-in-Human Phase I Study to Assess the Pharmacodynamic Profile of a Novel Potassium Channel Opener (XEN1101) on Human Cortical Excitability with TMS-EEG and TMS-EMG.” August 29, 2018

Company Presentation. Eilat XIV Meeting:  “XEN1101: A Novel, Next- Generation KCNQ2 Modulator for the Treatment of Epilepsy.” May 15, 2018

Company Presentation. Epilepsy Foundation Pipeline Conference: “XEN1101, a Novel Modulator of Kv7.2/3 for the Treatment of Epilepsy.” February 22-23, 2018

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XEN496 FOR EPILEPSY

Company Poster. Virtual 2020 American Epilepsy Society (AES) Annual Meeting: “Pharmacokinetic (PK) and Food Effect Assessment of XEN496, a Pediatric Formulation of Ezogabine, in Healthy Adults and Retrospective PK and Safety Comparison with Potiga.” December 4-8, 2020

Company Poster. 16th International Child Neurology Congress | 49th Annual Child Neurology Society Virtual Meeting: “Capturing Seizures in Clinical Trials of Anti-Seizure Medications (ASMs) for KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE).” October 12-23, 2020 

Company Poster. 16th International Child Neurology Congress | 49th Annual Child Neurology Society Virtual Meeting: “An Online Survey of Caregivers of Patients with KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE).” October 12-23, 2020 

Company Poster. 16th International Child Neurology Congress | 49th Annual Child Neurology Society Virtual Meeting: “Development of XEN496, a Pediatric Immediate-Release Formulation of the Potassium Channel Opener Ezogabine.” October 12-23, 2020 

Company Poster. 16th International Child Neurology Congress | 49th Annual Child Neurology Society Virtual Meeting: “Novel Microsampling Technique for Use in a Clinical Trial of Pediatric Patients with KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE).” October 12-23, 2020 

Company Presentation. 2020 Epilepsy Pipeline Conference:  “KV7 Potassium Channel Modulators for the Treatment of Epilepsy.” (Includes overview of both XEN1101 and XEN496) August 27, 2020

Company Presentation. Eilat XV Conference:  “New Anti-Epileptic Drugs and Devices.” (Same as above – includes overview of both XEN1101 and XEN496) July 28, 2020 

Company Poster. 2020 American Academy of Neurology (AAN) Meeting: “Pharmacokinetic and Food Effect Assessment of XEN496 (Pediatric Formulation of Ezogabine) in Healthy Adults and Relative Bioavailability Assessment with Potiga® (Adult Formulation of Ezogabine).” May 2020

Company Poster. 2020 American Academy of Neurology (AAN) Meeting: “An Online Survey of Caregivers of Patients with KCNQ2 Developmental & Epileptic Encephalopathy (KCNQ2-DEE): Focus on Ezogabine.” May 2020

Company Poster. 2020 American Academy of Neurology (AAN) Meeting: “Reliable Count of Seizures using Diaries versus Video Electroencephalography for Seizures of KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE)” May 2020

Company Poster. 2019 American Epilepsy Society (AES) Annual Meeting: “Development of XEN496, a Pediatric Immediate-Release Formulation of the Potassium Channel Opener Ezogabine.” December 6-10, 2019

Company Poster. 2019 American Epilepsy Society (AES) Annual Meeting–Genetic Epilepsies Scientific Exhibit: “An Online Survey of Caregivers of Patients with KCNQ2 Developmental & Epileptic Encephalopathy (KCNQ2-DEE): Focus on Ezogabine.” December 8, 2019

Company Poster. 2019 American Epilepsy Society (AES) Annual Meeting–Genetic Epilepsies Scientific Exhibit: “Development of XEN496, a Pediatric Immediate-Release Formulation of the Potassium Channel Opener Ezogabine, for the Treatment of KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE).” December 8, 2019

Kv7-related and supporting publications:

Tsuchida et al. Poster. 2019 American Epilepsy Society (AES) Annual Meeting–Genetic Epilepsies Scientific Exhibit: “ERGENT: Early Recognition of Genetic Epilepsy in Neonates.” December 8, 2019

Brodie et al. “Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy.” 2010 Neurology PubMed PMID: 20944074 

French et al. “Randomized, double-blind, placebocontrolled trial of ezogabine (retigabine) in partial epilepsy.” 2011 Neurology PubMed PMID: 21451152

Miceli, et al. “KCNQ2-Related Disorders.” 2016 GeneReviews PubMed

Millichap et al. “KCNQ2 encephalopathy: Features, mutational hot spots, and ezogabine treatment of 11 patients.” 2016 American Academy of Neurology PubMed PMID: 27602407

Ossemann et al. “Effect of a single dose of retigabine in cortical excitability parameters:A cross-over, double-blind placebo-controlled TMS study.” 2016 Epilepsy Research PubMed PMID: 27448328

Premoli et al. “The Effect of Lamotrigine and Levetiracetam on TMS-Evoked EEG Responses Depends on Stimulation Intensity.” 2017 Frontiers in Neuroscience PubMed PMID: 29104528

Premoli et al. “Lamotrigine and levetiracetam exert a similar modulation of TMS-evoked EEG potentials.” 2017 Epilepsia PubMed PMID: 27808418

Sachdeo, et al. “A novel design for a dose finding, safety, and drug interaction study of an antiepileptic drug (retigabine) in early clinical development.” 2014 International Journal of Clinical Pharmacology and Therapeutics PubMed PMID: 24755135

Weckhuysen et al. “KCNQ2 Encephalopathy: Emerging Phenotype of a Neonatal Epileptic Encephalopathy.” 2012 American Neurological Association PubMed PMID: 22275249

Weckhuysen et al. “Extending the KCNQ2 encephalopathy spectrum: Clinical and neuroimaging findings in 17 patients.” 2013 American Academy of Neurology PubMed PMID: 24107868

Ziemann et al. “TMS and drugs revisited.” 2015 Clinical Neurophysiology PubMed PMID: 25534482 

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NBI-921352 (XEN901): Partnered Program with Neurocrine Biosciences
Includes Selective Nav1.6 and Dual Nav1.2/1.6 Inhibitors

Company Poster. Virtual 2020 American Epilepsy Society (AES) Annual Meeting: “An Online Survey of Caregivers for Patients with SCN8A Developmental and Epileptic Encephalopathy (SCN8A-DEE) or SCN8A-Related Epilepsy.” December 4-8, 2020

Company Poster. Virtual 2020 American Epilepsy Society (AES) Annual Meeting: “Potential Drug-Drug Interactions Between NBI-921352/XEN901 (a Novel Nav1.6 Selective Sodium Channel Blocker) and a Strong Inducer of CYP3A4 (Phenytoin) in Healthy Volunteers.” December 4-8, 2020

Company Poster. Virtual 2020 American Epilepsy Society (AES) Annual Meeting: “Pharmacokinetics, Food Effect, and Relative Bioavailability of Two Formulations of NBI-921352/XEN901 (Novel Nav1.6-Selective Sodium Channel Blocker) in Healthy Adults: Pediatric Granules and Adult Tablets.” December 4-8, 2020

Company Poster. 2020 American Academy of Neurology (AAN) Meeting: “Relative Bioavailability, Pharmacokinetic and Food Effect Assessment of Two Immediate-Release Formulations of the NaV1.6-Selective Sodium Channel Blocker NBI-921352/XEN901: Pediatric Granules and Adult Tablets.” May 2020

Company Poster. 2020 American Academy of Neurology (AAN) Meeting: “Assessment of Potential Pharmacokinetic and Pharmacodynamic Interactions between NBI-921352/XEN901, a Novel NaV1.6-Selective Sodium Channel Blocker, and Phenytoin (a Non-selective NaV Blocker) in Adult Healthy Subjects.” May 2020

Company Poster. 2020 American Academy of Neurology (AAN) Meeting: “An Online Survey of Caregivers of Patients with SCN8A-Related Epilepsy.” May 2020

Company Poster. 2019 American Epilepsy Society (AES) Annual Meeting–Genetic Epilepsies Scientific Exhibit: “A Phase 1 Study in Healthy Subjects to Assess the Safety, Tolerability and Pharmacokinetics of XEN901, a Novel, Selective Nav1.6 Sodium Channel Inhibitor for the Treatment of SCN8A-Related Epilepsy.” December 8, 2019

Company Poster. 2019 American Epilepsy Society (AES) Annual Meeting–Genetic Epilepsies Scientific Exhibit: “An Online Survey of Caregivers of Patients with SCN8A-Related Epilepsy.” December 8, 2019

Company Poster. 2019 American Epilepsy Society (AES) Annual Meeting: “XEN393, A Novel Selective Dual Inhibitor of Nav1.2/Nav1.6 Channels Prevents Electrically-Induced Seizures in Mice and Rats.” December 6-10, 2019

Company Poster. 2019 American Epilepsy Society (AES) Annual Meeting: “Nav1.6 Selective and Nav1.2/Nav1.6 Dual Inhibitors Reduce Action Potential Firing in Mouse Cortical Pyramidal Neurons While Sparing Inhibitory Interneuron Firing.” December 6-10, 2019

Company Poster. 2018 American Epilepsy Society (AES) Annual Meeting: “A First in Human Phase 1 Study to Assess the Safety, Tolerability and Pharmacokinetics of a Novel NaV1.6 Selective Small Molecule Sodium Channel Inhibitor (XEN901) in Healthy Subjects.” December 3, 2018

Company Poster. 2018 American Epilepsy Society (AES) Annual Meeting: “Repeat Dosing of Novel Selective Inhibitors of NaV1.6 Enhances Efficacy in the Mouse Maximal Electroshock Model.” December 3, 2018

Company Poster. 2018 American Epilepsy Society (AES) Annual Meeting: “Efficacy of Sodium Channel Inhibitors as Anticonvulsants in the Rat MES Assay is
Predictive of the Therapeutic Plasma Concentration in Humans.” December 3, 2018

Company Poster. 2018 American Epilepsy Society (AES) Annual Meeting: “Preclinical Safety Margins of the Potent and NaV1.6 Selective Inhibitor, XEN901, in Relation to Non-Selective Sodium Channel Blockers.” December 3, 2018

Company Presentation. Eilat XIV Meeting:  “XEN901: A Novel, Highly Selective NaV1.6 Inhibitor for the Treatment of Epilepsy.” May 15, 2018

Company Poster. American Epilepsy Society Meeting: “Selective Inhibitors Suggest NaV1.6 Activity Is the Primary Driver of Efficacy for Voltage-Gated Sodium Channel Targeted AED’s.” December 2017

Company Poster. Society of General Physiologists Annual Meeting: “Selective antagonists of NaV1.6 prevent electrically induced seizures in a mouse model of EIEE13.” September 2016.

Related and supporting publications:

Veeramah et al. “De Novo Pathogenic SCN8A Mutation Identified by Whole-Genome Sequencing of a Family Quartet Affected by Infantile Epileptic Encephalopathy and SUDEP.” 2012 The American Journal of Human Genetics PubMed PMID: 22365152

Ohba et al. “Early onset epileptic encephalopathy caused by de novo SCN8A mutations.” 2014 Epilepsia PubMed PMID: 24888894

Meisler et al. “SCN8A encephalopathy: Research progress and prospects.” 2016 Epilepsia PubMed PMID: 27270488 

Hammer et al. “SCN8A-Related Epilepsy with Encephalopathy.”  GeneReviews PubMed PMID 27559564

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Other Selected Publications

Company Poster. Virtual 2020 American Epilepsy Society (AES) Annual Meeting: “Early Data from a Phase 2 Open Label Study of XEN007 (Flunarizine) for Treatment Resistant Absence Seizures.” December 4-8, 2020

Company Poster. Virtual 2020 American Epilepsy Society (AES) Annual Meeting: “Selective Potentiation of Inhibitory Networks Prevents Seizures in a Mouse Model of Dravet Syndrome.” December 4-8, 2020

Company Poster. 2019 American Epilepsy Society (AES) Annual Meeting: “Small Molecule Potentiators of Nav1.1. Increase Action Potential Firing in Fast Spiking Cortical Inhibitory Interneurons from a Mouse Model of Dravet Syndrome.” December 6-10, 2019

Company Poster. 2019 American Epilepsy Society (AES) Annual Meeting– Genetic Epilepsies Scientific Exhibit: “Selective Sodium Channel Inhibitors and Potentiators; Pharmacology in Cortical Slices from Wild-Type and Dravet Mice.” December 6-10, 2019

Focken T, Chowdhury S, Zenova A, Grimwood ME, Chabot C, Sheng T, Hemeon I, Decker SM, Wilson M, Bichler P, Jia Q, Sun S, Young C, Lin S, Goodchild SJ, Shuart NG, Chang E, Xie Z, Li B, Khakh K, Bankar G, Waldbrook M, Kwan R, Nelkenbrecher K, Karimi Tari P, Chahal N, Sojo L, Robinette CL, White AD, Chen CA, Zhang Y, Pang J, Chang JH, Hackos DH, Johnson JP, Cohen CJ, Ortwine DF, Sutherlin DP, Dehnhardt CM, Safina BS. “Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification of N-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)methane-sulfonamides as Potent and Selective hNaV1.7 Inhibitors for the Treatment of Pain.” PubMed PMID: 29737846

Chernov-Rogan T, Li T, Lu G, Verschoof H, Khakh K, Jones SW, Beresini MH, Liu C, Ortwine DF, McKerrall SJ, Hackos DH, Sutherlin D, Cohen CJ, Chen J. “Mechanism-specific assay design facilitates the discovery of Nav1.7-selective inhibitors.” Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):E792-E801  PubMed PMID: 29311306

Winquist RJ, Cohen CJ.  “Integration of biological/pathophysiological contexts to help clarify genotype-phenotype mismatches in monogenetic diseases. Childhood epilepsies associated with SCN2A as a case study. Biochem Pharmacol.” 2018 May;151:252-262.  PubMed PMID: 29307654

Focken T, Liu S, Chahal N, Dauphinais M, Grimwood ME, Chowdhury S, Hemeon I, Bichler P, Bogucki D, Waldbrook M, Bankar G, Sojo LE, Young C, Lin S, Shuart N, Kwan R, Pang J, Chang JH, Safina BS, Sutherlin DP, Johnson JP Jr, Dehnhardt CM, Mansour TS, Oballa RM, Cohen CJ, Robinette CL. “Discovery of Aryl Sulfonamides as Isoform-Selective Inhibitors of NaV1.7 with Efficacy in Rodent Pain Models.” ACS Med Chem Lett. 2016 Jan 19;7(3):277-82. PubMed PMID: 26985315

Huang, J, Vanoye CG, Cutts A, Goldberg YP, Dib-Hajj SD, Cohen CJ, Waxman SG, George AL Jr. “Sodium channel Nav1.9 mutations associated with insensitivity to pain dampen neuronal excitability.”  J Clin Invest. 2017 June 30; 127(7):2805-2814.  PubMed PMID: 28530638

Ahuja S, Mukund S, Deng L, Khakh K, Chang E, Ho H, Shriver S, Young C, Lin S, Johnson JP Jr, Wu P, Li J, Coons M, Tam C, Brillantes B, Sampang H, Mortara K, Bowman KK, Clark KR, Estevez A, Xie Z, Verschoof H, Grimwood M, Dehnhardt C, Andrez JC, Focken T, Sutherlin DP, Safina BS, Starovasnik MA, Ortwine DF, Franke Y, Cohen CJ, Hackos DH, Koth CM, Payandeh J. “Structural basis of NaV7 inhibition by an isoform-selective small-molecule antagonist.” Science. 2015 Dec 18;350(6267) PubMed PMID: 26680203

Sun S, Jia Q, Zenova AY, Chafeev M, Zhang Z, Lin S, Kwan R, Grimwood ME, Chowdhury S, Young C, Cohen CJ, Oballa RM. “The discovery of benzenesulfonamide-based potent and selective inhibitors of voltage-gated sodium channel Nav1.7.” Bioorg Med Chem Let 2014 August, 24(2):4397-4401. PubMed PMID: 25176194

Goldberg YP, Pimstone SN, Namdari R, Price N, Cohen C, Sherrington RP, Hayden MR. “Human Mendelian pain disorders: a key to discovery and validation of novel analgesics.” Clin Genet. 2012 Oct;82(4):367-73. PubMed PMID: 22845492

Goldberg YP, MacFarlane J, MacDonald ML, Thompson J, Dube MP, Mattice M, Fraser R, Young C, Hossain S, Pape T, Payne B, Radomski C, Donaldson G, Ives E, Cox J, Younghusband HB, Green R, Duff A, Boltshauser E, Grinspan GA, Dimon JH, Sibley BG, Andria G, Toscano E, Kerdraon J, Bowsher D, Pimstone SN, Samuels ME, Sherrington R, Hayden MR. “Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations.” Clin. Genet. 71(4):311-319, Apr. 2007. PubMed PMID: 17470132