{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:24:26Z","timestamp":1791606266005,"version":"4.3.4"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Astegolimab, a fully human immunoglobulin G2 monoclonal antibody, binds with high affinity to ST2, the interleukin\u201033 receptor, thereby blocking ST2\/interleukin\u201033 binding and subsequent inflammatory cascades involved in inflammatory diseases. Here, we present three randomized, double\u2010blind, placebo\u2010controlled, Phase I studies evaluating the safety, tolerability, pharmacokinetics, and immunogenicity of single\u2010ascending doses of astegolimab in healthy participants and patients with mild atopic asthma (NCT01928368), multiple\u2010ascending doses in healthy participants (NCT02170337), and single\u2010ascending doses in healthy Japanese and White adults. Overall, 152 participants were enrolled, randomized, and treated with single\u2010 or multiple\u2010ascending doses of astegolimab (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009112) or placebo (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200940) subcutaneously (2.1\u2013560\u2009mg) or intravenously (210 or 700\u2009mg). No deaths, serious adverse events, or discontinuations due to adverse events occurred during the studies. No clinically meaningful differences in incidence of TEAEs were observed between treatment arms. Pharmacokinetic exposure increased more than dose proportionally over 2.1\u2013420\u2009mg for single\u2010ascending doses but were approximately dose proportional for single\u2010 and multiple\u2010ascending doses \u2265\u200970\u2009mg following subcutaneous administration. No pharmacokinetic differences were observed based on ethnicity between Japanese and White participants following body weight adjustments. Incidence of antidrug antibodies to astegolimab in healthy participants in the single\u2010 and multiple\u2010ascending dose studies was 14%\u201323% and 33%\u201350% for subcutaneous and intravenous administration, respectively. Astegolimab was well tolerated in these Phase I studies with no safety concerns identified. Thus, further assessment of astegolimab in targeted patient populations was justified; the Phase IIb ALIENTO and Phase III ARNASA trials in patients with chronic obstructive pulmonary disease are ongoing.\n                  <\/jats:p>","DOI":"10.1111\/cts.70338","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T10:42:14Z","timestamp":1759401734000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Safety, Pharmacokinetics, and Immunogenicity of Astegolimab, an\n                    <scp>Anti\u2010ST2<\/scp>\n                    Monoclonal Antibody, in Randomized, Phase I Clinical Studies"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0857-5410","authenticated-orcid":false,"given":"Wenhui","family":"Zhang","sequence":"first","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy","family":"Cheung","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Fong","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9215-408X","authenticated-orcid":false,"given":"Logan","family":"Brooks","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele A.","family":"Grimbaldeston","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Arjomandi","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Yang","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajit","family":"Dash","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hansen","family":"Wong","sequence":"additional","affiliation":[{"name":"Amgen Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane R.","family":"Parnes","sequence":"additional","affiliation":[{"name":"Amgen Inc.  Thousand Oaks California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Mohan","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0144-2022"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24108702"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12619"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.11.001"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-021-01423-8"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2660"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11010056"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00473.2020"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00556-7"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000005716"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.03.044"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.08.015"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200801-060ST"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio-2023-0115"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1545"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2021"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2017.06.002"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.1.124"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704916200"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00305.2014"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2020-214712"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00580"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13157"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70338","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T05:31:57Z","timestamp":1761370317000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70338"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":23,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/cts.70338"],"URL":"https:\/\/doi.org\/10.1111\/cts.70338","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2025-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70338"}}