{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T13:56:10Z","timestamp":1781186170492,"version":"3.54.1"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>This Phase 1a\/b clinical study evaluated the safety, tolerability, pharmacodynamics (PD) response, and antiviral activity of GS\u20104224, a first\u2010in\u2010class, programmed death\u2010ligand 1 (PD\u2010L1)\u2010binding orally bioavailable small molecule.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants were randomised to single and multiple ascending doses (S\/MAD) of GS\u20104224 or placebo\u2010to\u2010match (PTM). Healthy participants (HPs; 5 cohorts) received once\u2010daily GS\u20104224 doses for 10\u2009days, escalating from 20 to 1 000\u2009mg. Participants with chronic hepatitis B (CHB; 5 cohorts) received once\u2010daily GS\u20104224 100, 300, or 700\u2009mg for 28\u2009days. The primary objective was GS\u20104224 safety and tolerability. PD markers in peripheral blood cells and the mean change in hepatitis B surface antigen (HBsAg) were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 60 HPs and 42 participants with CHB received GS\u20104224, and 15 and 10 received PTM. There were no Grade \u2265\u20093 adverse events (AEs), serious AEs, or deaths among HPs. No participants with CHB experienced serious AEs or death. Grade \u2265\u20093 AEs occurred in 2 viremic participants (unrelated Grade 3 AE of acute exacerbation of hepatitis B [detected prior to GS\u20104224 dosing] leading to study discontinuation; related Grade 3 AE of increased alanine aminotransferase). PD\u2010L1 receptor occupancy on cells with low PD\u2010L1 expression was dose\u2010dependent and peaked at 38% among HPs who received MAD of GS\u20104224 1 000\u2009mg and 35% among participants with CHB who received MAD of GS\u20104224 700\u2009mg. No changes in HBsAg levels were observed in participants with CHB who received GS\u20104224.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In all participants, GS\u20104224 was generally safe and well tolerated; however, no antiviral effect was detected at the doses evaluated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70695","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T07:09:44Z","timestamp":1779347384000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety, Tolerability, and Pharmacodynamics of\n                    <scp>GS<\/scp>\n                    \u20104224 in Healthy Participants and Participants With Chronic Hepatitis B"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4086-7955","authenticated-orcid":false,"given":"Edward J.","family":"Gane","sequence":"first","affiliation":[{"name":"University of Auckland Auckland  New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi\u2010Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Ditmanson Medical Foundation Chiayi Christian Hospital  Chiayi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4507-2414","authenticated-orcid":false,"given":"Cheng\u2010Hao","family":"Tseng","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology E\u2010Da Cancer Hospital  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3007-3190","authenticated-orcid":false,"given":"Chun\u2010Yen","family":"Lin","sequence":"additional","affiliation":[{"name":"Chang Gung University, Chang Gung Memorial Hospital Linkou Branch  Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart K.","family":"Roberts","sequence":"additional","affiliation":[{"name":"The Alfred Hospital and Monash University Melbourne  Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Tedesco","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. 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