{"id":"https://openalex.org/W4416638138","doi":"https://doi.org/10.1183/13993003.congress-2025.oa5392","title":"Mechanistic Drivers for Potent Pharmacodynamic Activity of Verekitug, a novel anti-TSLPR antibody","display_name":"Mechanistic Drivers for Potent Pharmacodynamic Activity of Verekitug, a novel anti-TSLPR antibody","publication_year":2025,"publication_date":"2025-09-27","ids":{"openalex":"https://openalex.org/W4416638138","doi":"https://doi.org/10.1183/13993003.congress-2025.oa5392"},"language":"en","primary_location":{"id":"doi:10.1183/13993003.congress-2025.oa5392","doi":"https://doi.org/10.1183/13993003.congress-2025.oa5392","is_oa":false,"landing_page_url":"https://doi.org/10.1183/13993003.congress-2025.oa5392","pdf_url":null,"source":{"id":"https://openalex.org/S4210207896","display_name":"European Respiratory Journal","issn_l":"0903-1936","issn":["0903-1936","1399-3003"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310317833","host_organization_name":"European Respiratory Society","host_organization_lineage":["https://openalex.org/P4310317833"],"host_organization_lineage_names":["European Respiratory Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Allergy and immunology","raw_type":"proceedings-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5089088185","display_name":"Ashish V. Kalra","orcid":"https://orcid.org/0000-0002-3608-7502","observed_orcids":["https://orcid.org/0000-0002-3608-7502"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ashish Kalra","raw_affiliation_strings":["1Upstream Bio, Waltham, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Upstream Bio, Waltham, United States","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085434927","display_name":"Fatema Z. Chowdhury","orcid":"https://orcid.org/0000-0003-3443-0431","observed_orcids":["https://orcid.org/0000-0003-3443-0431"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Fatema Chowdhury","raw_affiliation_strings":["1Upstream Bio, Waltham, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Upstream Bio, Waltham, United States","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5039854274","display_name":"Sumathi Sivapalasingam","orcid":"https://orcid.org/0009-0001-9735-5793","observed_orcids":["https://orcid.org/0009-0001-9735-5793"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sumathi Sivapalasingam","raw_affiliation_strings":["1Upstream Bio, Waltham, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Upstream Bio, Waltham, United States","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5072872904","display_name":"Aaron Deykin","orcid":"https://orcid.org/0009-0005-7408-8812","observed_orcids":["https://orcid.org/0009-0005-7408-8812"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Aaron Deykin","raw_affiliation_strings":["1Upstream Bio, Waltham, United States"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Upstream Bio, Waltham, United States","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":"OA5392","last_page":"OA5392"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10051","display_name":"Asthma and respiratory diseases","score":0.98580002784729,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10051","display_name":"Asthma and respiratory diseases","score":0.98580002784729,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.002899999963119626,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11503","display_name":"Cytokine Signaling Pathways and Interactions","score":0.0026000000070780516,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/tezepelumab","display_name":"tezepelumab","score":0.890999972820282},{"id":"https://openalex.org/keywords/tslp-receptor","display_name":"TSLP receptor","score":0.8349999785423279},{"id":"https://openalex.org/keywords/stat5-signaling","display_name":"STAT5 signaling","score":0.7329999804496765},{"id":"https://openalex.org/keywords/exhaled-nitric-oxide","display_name":"exhaled nitric oxide","score":0.8420000076293945},{"id":"https://openalex.org/keywords/severe-asthma","display_name":"severe asthma","score":0.5820000171661377},{"id":"https://openalex.org/keywords/chronic-rhinosinusitis-with-nasal-polyps","display_name":"chronic rhinosinusitis with nasal polyps","score":0.9570000171661377},{"id":"https://openalex.org/keywords/chronic-obstructive-pulmonary-disease","display_name":"chronic obstructive pulmonary disease","score":0.890999972820282}],"concepts":[{"id":"https://openalex.org/C57992300","wikidata":"https://www.wikidata.org/wiki/Q2066956","display_name":"Potency","level":3,"score":0.8098999857902527},{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.7261999845504761},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.7167999744415283},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.6359000205993652},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5789999961853027},{"id":"https://openalex.org/C542903549","wikidata":"https://www.wikidata.org/wiki/Q422248","display_name":"Monoclonal antibody","level":3,"score":0.5662999749183655},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.5360000133514404},{"id":"https://openalex.org/C2779391668","wikidata":"https://www.wikidata.org/wiki/Q4210018","display_name":"STAT5","level":3,"score":0.49540001153945923},{"id":"https://openalex.org/C519581460","wikidata":"https://www.wikidata.org/wiki/Q207843","display_name":"Nitric oxide","level":2,"score":0.4551999866962433},{"id":"https://openalex.org/C2776120743","wikidata":"https://www.wikidata.org/wiki/Q3271540","display_name":"Mechanism of action","level":3,"score":0.4551999866962433},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.44269999861717224},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.4004000127315521},{"id":"https://openalex.org/C159654299","wikidata":"https://www.wikidata.org/wiki/Q79460","display_name":"Antibody","level":2,"score":0.3652999997138977},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.3549000024795532},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.3409999907016754},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.3156000077724457},{"id":"https://openalex.org/C2776885963","wikidata":"https://www.wikidata.org/wiki/Q245204","display_name":"Antagonist","level":3,"score":0.3091999888420105},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.28519999980926514},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.2808000147342682},{"id":"https://openalex.org/C38533456","wikidata":"https://www.wikidata.org/wiki/Q1671589","display_name":"Intrinsic activity","level":4,"score":0.2799000144004822},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.275299996137619},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.27070000767707825},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.26739999651908875},{"id":"https://openalex.org/C64903051","wikidata":"https://www.wikidata.org/wiki/Q2198549","display_name":"Drug development","level":3,"score":0.258899986743927}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1183/13993003.congress-2025.oa5392","doi":"https://doi.org/10.1183/13993003.congress-2025.oa5392","is_oa":false,"landing_page_url":"https://doi.org/10.1183/13993003.congress-2025.oa5392","pdf_url":null,"source":{"id":"https://openalex.org/S4210207896","display_name":"European Respiratory Journal","issn_l":"0903-1936","issn":["0903-1936","1399-3003"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310317833","host_organization_name":"European Respiratory Society","host_organization_lineage":["https://openalex.org/P4310317833"],"host_organization_lineage_names":["European Respiratory Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Allergy and immunology","raw_type":"proceedings-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9537000060081482,"id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W7117119520","https://openalex.org/W4410268410","https://openalex.org/W4405263459","https://openalex.org/W2604165347","https://openalex.org/W3180912802","https://openalex.org/W4386843689","https://openalex.org/W4402522298","https://openalex.org/W2975181559","https://openalex.org/W4281825920","https://openalex.org/W4404104222"],"abstract_inverted_index":{"Background:":[0],"Verekitug,":[1],"a":[2,76,152,170],"fully":[3],"human":[4],"monoclonal":[5],"antibody":[6],"antagonist":[7],"of":[8,45,50,57,100,146,173,185],"TSLP":[9,121,126,150],"receptor,":[10],"is":[11,151],"currently":[12],"being":[13],"developed":[14],"for":[15,34,161,175],"severe":[16],"asthma,":[17],"CRSwNP":[18],"and":[19,26,59,66,86,92,122,128],"COPD.":[20],"Verekitug":[21,110,124],"demonstrates":[22],"superior":[23],"in":[24,75,102,138],"vitro":[25],"clinical":[27,97],"pharmacodynamic":[28,98],"potency":[29,49,184],"compared":[30,52,148,163,191],"to":[31,53,112,120,149,155,164,192],"published":[32],"data":[33,168],"tezepelumab,":[35],"an":[36],"anti-TSLP":[37],"antibody.":[38],"Objective:":[39],"To":[40],"understand":[41],"the":[42,46,95,142,156,181,193],"mechanistic":[43],"drivers":[44],"higher":[47],"relative":[48],"verekitug":[51,58,101,162,176,189],"tezepelumab.":[54,165],"Methods:":[55],"Interactions":[56],"TSLP/TSLPR/IL7R\u03b1":[60],"complex":[61],"were":[62,90],"investigated":[63],"with":[64,94,114,117,188],"biochemical":[65],"molecular":[67],"assays.":[68],"TSLP-induced":[69],"STAT5":[70,135],"signal":[71],"inhibition":[72],"was":[73],"measured":[74],"cell-based":[77],"assay.":[78],"In":[79],"silico":[80,139],"model":[81,140],"incorporating":[82],"drug":[83],"affinity,":[84],"PK":[85],"TSLP/TSLPR":[87],"pathway":[88],"parameters":[89],"built":[91],"co-fit":[93],"observed":[96,160,182],"effects":[99],"fractional":[103],"exhaled":[104],"nitric":[105],"oxide":[106],"(FeNO)":[107],"suppression.":[108],"Results:":[109],"binds":[111],"TSLPR":[113,147,187],"sub-picomolar":[115],"affinity":[116],"no":[118],"binding":[119,127],"IL7R\u03b1.":[123],"outcompetes":[125],"disrupts":[129],"TSLP/TSLPR/IL7Ra":[130],"complex,":[131],"thereby":[132],"inhibiting":[133],"downstream":[134],"signaling.":[136],"The":[137],"indicates":[141],"lower":[143],"steady-state":[144],"concentrations":[145],"likely":[153],"contributor":[154],"greater":[157,183],"FeNO":[158],"reductions":[159],"Conclusion:":[166],"These":[167],"reveal":[169],"novel":[171],"mechanism":[172],"action":[174],"that":[177],"may":[178],"contribute":[179],"towards":[180],"targeting":[186],"as":[190],"ligand.":[194],"erj;66/suppl_69/OA5392/F1":[195],"F1":[196,197]},"counts_by_year":[],"updated_date":"2026-11-01T11:40:01.658920","created_date":"2025-11-25T00:00:00"}