Publications


XEN1101 FOR EPILEPSY

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

Related and supporting publications:

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 

 XEN901 FOR EPILEPSY

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

Other Selected Publications

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