{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:47:12Z","timestamp":1792021632732,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>Verekitug, a novel, high\u2010affinity, fully human monoclonal antibody targeting thymic stromal lymphopoietin receptor (TSLPR), is in development as a potential treatment for severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and chronic obstructive pulmonary disease (COPD). This phase 1b, double\u2010blind, randomized, placebo\u2010controlled, multiple ascending\u2010dose trial assessed the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of verekitug administered subcutaneously in patients with mild\u2013moderate asthma. Thirty\u2010two participants were randomized in 4 placebo\u2010controlled dosing cohorts (3\u2009\u00d7\u2009100\u2010mg or 200\u2010mg doses, once every 4\u2009weeks; 2\u2009\u00d7\u2009300\u2010mg doses, once every 12\u2009weeks; single 25\u2010mg dose) and observed for 32\u2009weeks. The primary endpoint was safety; secondary endpoints were pharmacokinetics and immunogenicity. Exploratory endpoints included TSLPR occupancy and biomarker effects. Treatment\u2010emergent adverse events were mild or moderate. Complete TSLPR occupancy was observed at the first timepoint (2\u2009weeks post dose) and maintained for 24\u2009weeks (doses \u2265100\u2009mg). Rapid mean reductions in fractional exhaled nitric oxide, eosinophils, and interleukin\u20105 (up to \u221254%, \u221265%, and \u221264%, respectively) were sustained up to 24\u2009weeks (doses \u2265100\u2009mg). The mean verekitug half\u2010life was ~20\u2009days. Low\u2010titer antidrug antibody response was observed in some participants, without clinically meaningful impact on pharmacokinetics, pharmacodynamics, or safety. Verekitug was generally well tolerated, with rapid, substantial, and sustained effects on asthma biomarkers. These findings support further development of verekitug for treating severe asthma, CRSwNP, and COPD.<\/jats:p>","DOI":"10.1002\/cpt.70156","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T12:41:58Z","timestamp":1766580118000},"page":"782-790","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Verekitug, a Novel Antibody Antagonist to the\n                    <scp>TSLP<\/scp>\n                    Receptor in Adults with Asthma: A 32\u2010Week Randomized Phase 1b Multiple Ascending\u2010Dose Trial"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8918-7075","authenticated-orcid":false,"given":"Dave","family":"Singh","sequence":"first","affiliation":[{"name":"Medicines Evaluation Unit  Manchester UK"},{"name":"University of Manchester, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4258-9036","authenticated-orcid":false,"given":"Chaim M.","family":"Brickman","sequence":"additional","affiliation":[{"name":"Chaim Brickman Consulting Ltd.  Zur Hadassah Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2337-7459","authenticated-orcid":false,"given":"Peter","family":"Lloyd","sequence":"additional","affiliation":[{"name":"KinDyn Consulting Ltd.  Warnham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Kalra","sequence":"additional","affiliation":[{"name":"Upstream Bio Inc.  Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1250-7135","authenticated-orcid":false,"given":"Subhabrata","family":"Biswas","sequence":"additional","affiliation":[{"name":"Upstream Bio Inc.  Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9432-3956","authenticated-orcid":false,"given":"Arkadeep","family":"Sinha","sequence":"additional","affiliation":[{"name":"Upstream Bio Inc.  Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9751-6940","authenticated-orcid":false,"given":"Alex","family":"Mulvanny","sequence":"additional","affiliation":[{"name":"Medicines Evaluation Unit  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9735-5793","authenticated-orcid":false,"given":"Sumathi","family":"Sivapalasingam","sequence":"additional","affiliation":[{"name":"Upstream Bio Inc.  Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7885-0043","authenticated-orcid":false,"given":"Oren M.","family":"Becker","sequence":"additional","affiliation":[{"name":"Oren Becker Consulting Ltd.  Mevasseret Zion Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7408-8812","authenticated-orcid":false,"given":"Aaron","family":"Deykin","sequence":"additional","affiliation":[{"name":"Upstream Bio Inc.  Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"e_1_2_11_1_1","unstructured":"Global Initiative for Asthma.Global Strategy for Asthma Management and Prevention Updated May 2024(2024)."},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0238-2023"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2021.08.416"},{"key":"e_1_2_11_4_1","article-title":"Anti\u2010IL5 therapies for asthma","volume":"9","author":"Farne H.A.","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2022.11.008"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2024.16.3.253"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/02770903.2018.1520865"},{"key":"e_1_2_11_8_1","article-title":"Omalizumab for asthma in adults and children","volume":"2014","author":"Normansell R.","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_11_9_1","unstructured":"Tezspire.Package insert. Amgen Inc. and AstraZeneca(2023)."},{"key":"e_1_2_11_10_1","unstructured":"Cinqair.Package insert. Teva Respiratory(2020)."},{"key":"e_1_2_11_11_1","unstructured":"Fasenra.Package insert. AstraZeneca(2024)."},{"key":"e_1_2_11_12_1","unstructured":"Nucala.Package insert. GlaxoSmithKline(2023)."},{"key":"e_1_2_11_13_1","unstructured":"Xolair.Package insert. Genentech Inc. a member of the Roche Group(2024)."},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.975914"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062211"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2147\/JAA.S342391"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/76923"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14937"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25115972"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13133721"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.08.031"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.05.033"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.08.031"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402895"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701455"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.11.915"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-86179-1"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2020.10.008"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1704064"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034975"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00226-5"},{"key":"e_1_2_11_32_1","article-title":"A phase 1, first\u2010in\u2010human, single ascending\u2010dose study with a novel antibody to the human thymic stromal lymphopoietin receptor","volume":"207","author":"Deykin A.B.","year":"2023","journal-title":"Am J Respir Crit Care Med"},{"key":"e_1_2_11_33_1","unstructured":"A Study to Investigate the Efficacy and Safety of Verekitug (UPB\u2010101) in Participants With Chronic Rhinosinusitis With Nasal Polyps<https:\/\/clinicaltrials.gov\/study\/NCT06164704> (2024). Accessed December 24 2024."},{"key":"e_1_2_11_34_1","unstructured":"A Study to Investigate the Efficacy and Safety of Verekitug (UPB\u2010101) in Adult Participants With Severe Asthma (VALIANT)<https:\/\/clinicaltrials.gov\/study\/NCT06196879> (2024). Accessed December 24 2024."},{"key":"e_1_2_11_35_1","unstructured":"Upstream Bio.Upstream bio announces oral presentation of new data from a phase 1b multiple ascending dose trial of verekitug (UPB\u2010101) in adults with asthma at the European Respiratory Congress<https:\/\/upstreambio.com\/press\u2010releases\/oral\u2010presentation\u2010data\u2010phase\u20101b\u2010multiple\u2010ascending\u2010dose\u2010trial\u2010verekitug\u2010upb\u2010101\u2010asthma\u2010european\u2010respiratory\u2010society\u2010congress\/> (2024). Accessed January 23 2025."},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.121.000686"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2019.05.005"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000793"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2032506"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01461-2024"},{"key":"e_1_2_11_41_1","unstructured":"Dupixent.Package insert. Regeneron(2024)."},{"key":"e_1_2_11_42_1","first-page":"17","article-title":"Global Initiative for Asthma Strategy 2021: Executive summary and rationale for key changes","volume":"205","author":"Reddel H.K.","year":"2022","journal-title":"Eur Respir J"},{"key":"e_1_2_11_43_1","first-page":"1098","article-title":"Extending human IgG half\u2010life using structure\u2010guided design","volume":"10","author":"Booth B.J.","year":"2018","journal-title":"MAbs"},{"key":"e_1_2_11_44_1","unstructured":"Upstream Bio.Upstream Bio announces dosing of first patients in a phase 2 clinical trial of verekitug (UPB\u2010101) in chronic rhinosinusitis with nasal polyps (CRSwNP)<https:\/\/upstreambio.com\/press\u2010releases\/upstream\u2010bio\u2010announces\u2010dosing\u2010of\u2010first\u2010patients\u2010in\u2010a\u2010phase\u20102\u2010clinical\u2010trial\u2010of\u2010verekitug\u2010upb\u2010101\u2010in\u2010chronic\u2010rhinosinusitis\u2010with\u2010nasal\u2010polyps\u2010crswnp\/> (2024). 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