{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:59:57Z","timestamp":1785373197248,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Ginisortamab, a first\u2010in\u2010class human monoclonal antibody for the treatment of advanced solid tumours, binds to gremlin\u20101 and restores bone morphogenetic protein signalling. We used pharmacokinetic\/pharmacodynamic (PK\/PD) modelling to characterize the relationship between ginisortamab dose and serum gremlin\u20101 binding, using model\u2010based simulations to inform ginisortamab\u2010dose selection for ongoing clinical development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Ginisortamab and total gremlin\u20101 serum concentration data were obtained from the monotherapy dose\u2010escalation module of the ONC001 phase 1\/2 multipart study in participants with solid tumours (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04393298\">NCT04393298<\/jats:ext-link>\n                      ). Population PK\/PD models were generated using an iterative model\u2010building process with nonlinear mixed effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A two\u2010compartment PK model with first\u2010order drug elimination adequately described dose\u2010proportional exposure for ginisortamab 100\u20132000\u2009mg (administered every 2\u2009weeks via intravenous infusion). PK\/PD modelling incorporating total gremlin\u20101 serum concentrations adequately described ginisortamab binding to serum gremlin\u20101. Body surface area significantly affected central (\n                      <jats:italic>V<\/jats:italic>\n                      <jats:sub>c<\/jats:sub>\n                      , 1.3 [95% CI: 1.0\u20131.7]) and peripheral (\n                      <jats:italic>V<\/jats:italic>\n                      <jats:sub>p<\/jats:sub>\n                      , 2.2 [95% CI: 1.6\u20133.0]) volume of distribution of ginisortamab, but no other tested covariates impacted ginisortamab\u2013gremlin\u20101 binding kinetics. Estimated gremlin\u20101 turnover time was rapid (~23 [95% CI: ~18\u201332]\u00a0min). The developed PK\/PD model was used to simulate ginisortamab dosing regimens; 1000\u2009mg once\u2010weekly and 2000\u2009mg every 2\u2009weeks were predicted to maintain target suppression \u226590% over the dosing interval at steady state.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This population PK\/PD model adequately described ginisortamab PK and binding to serum gremlin\u20101 in patients with advanced solid tumours. Dose simulations informed the level of gremlin\u20101 suppression and supported further clinical evaluation of several dosing regimens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70567","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T06:30:59Z","timestamp":1777617059000},"page":"2885-2898","source":"Crossref","is-referenced-by-count":0,"title":["A dose\u2010finding population pharmacokinetic\/pharmacodynamic model of ginisortamab, an anti\u2010gremlin\u20101 monoclonal antibody, in patients with solid tumours"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8577-3277","authenticated-orcid":false,"given":"Yin Cheong","family":"Wong","sequence":"first","affiliation":[{"name":"UCB Quantitative Clinical Pharmacology  Slough UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa Rojas","family":"Chavarro","sequence":"additional","affiliation":[{"name":"Parexel International Clinical Pharmacology, Modeling and Simulation  Bogota Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Jones","sequence":"additional","affiliation":[{"name":"UCB Precision Medicine  Slough UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Egging","sequence":"additional","affiliation":[{"name":"UCB Precision Medicine  Braine L'Alleud Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanchana","family":"Ungphakorn","sequence":"additional","affiliation":[{"name":"Parexel International Clinical Pharmacology, Modeling and Simulation  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Valle","sequence":"additional","affiliation":[{"name":"Parexel International Clinical Pharmacology, Modeling and Simulation  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Matthews","sequence":"additional","affiliation":[{"name":"UCB Clinical Science  Braine L'Alleud Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.vh.2015.06.004"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2017.10.002"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606857103"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10020301"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058\u2010019\u20101194\u20100"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11142136"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010020\u20100945\u20100"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21239227"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010019\u20100467\u20107"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3750"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27842"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.4_suppl.TPS221"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2015.4367"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.21873\/cgp.20167"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.030"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.36886"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535\u2010012\u20100614\u2010z"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1758834016646734"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2023.2289681"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12082149"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.11.011"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538\u20107445.Am2023\u2010ct094"},{"key":"e_1_2_10_25_1","unstructured":"ICH E6 (R1) guideline for Good Clinical Practice \u2010 Revision 1. 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