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Reduction in blood eosinophil count (BEC), a biomarker of IL\u20105 activity, is commonly used to evaluate the efficacy of anti\u2010IL\u20105 biologic therapies. Model\u2010informed drug development (MIDD) and quantitative decision making (QDM) were used to shorten the clinical development of depemokimab (an ultra\u2010long\u2010acting anti\u2010IL\u20105 biologic). A Bayesian nonlinear mixed effects dose\u2013time response model predicted the depemokimab dose in severe asthma achieving comparable BEC reductions to those observed in mepolizumab (an approved anti\u2010IL\u20105 biologic) Phase III MUSCA and MENSA trials. Prespecified QDM go\/no\u2010go criteria were applied to assess success probability. Phase IIb efficacy\u2010based trial simulations were conducted using negative binomial distribution to simulate individual annualized exacerbation rate. A depemokimab PK\/PD (BEC) model predicted Phase III trial doses in CRSwNP\/EGPA\/HES. Single depemokimab doses were well\u2010described by the Bayesian model; a single depemokimab dose \u2265\u200960\u2009mg had probability \u2265\u200980% of exceeding Minimum (78%; MUSCA) and \u2265\u200910% probability of exceeding Target (84%; MENSA) values for trough BEC reduction from baseline vs. placebo. Clinical trial simulations demonstrated &lt;\u20093% probability of more precise estimation of the Phase III dosing regimen with a conventional efficacy\u2010based dose\u2010ranging study. Depemokimab 100\u2009mg for severe asthma\/CRSwNP and 200\u2009mg for EGPA\/HES, administered subcutaneously every 26\u2009weeks, were selected for Phase III trials. MIDD and QDM shortened the depemokimab development program by 2\u20133\u2009years, emphasizing the potential of this approach for progressing new therapies from Phase I directly to Phase III.<\/jats:p>","DOI":"10.1002\/cpt.70183","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T08:42:45Z","timestamp":1768898565000},"page":"1005-1015","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Straight to Phase\n                    <scp>III<\/scp>\n                    : Model\u2010Informed Approach Speeds Depemokimab Clinical Development in Interleukin\u20105\u2010Driven Diseases"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9562-8826","authenticated-orcid":false,"given":"Chiara","family":"Zecchin","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Modelling and Simulation GSK  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8204-5242","authenticated-orcid":false,"given":"Stein","family":"Schalkwijk","sequence":"additional","affiliation":[{"name":"GSK  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6460-4538","authenticated-orcid":false,"given":"Isabelle J.","family":"Pouliquen","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modelling and Simulation GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7078-327X","authenticated-orcid":false,"given":"Alienor","family":"Berges","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology GSK  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Bird","sequence":"additional","affiliation":[{"name":"Biostatistics GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0595-4802","authenticated-orcid":false,"given":"Richard","family":"Follows","sequence":"additional","affiliation":[{"name":"Clinical Sciences \u2013 Respiratory Immunology &amp; Inflammation Unit (RIIRU), GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9346-5071","authenticated-orcid":false,"given":"Daren","family":"Austin","sequence":"additional","affiliation":[{"name":"Business Development GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.33590\/emj\/HTIQ1028"},{"key":"e_1_2_11_2_1","unstructured":"European Medicines Agency.NUCALA (mepolizumab) Summary of Product Characteristics<https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/nucala\u2010epar\u2010product\u2010information_en.pdf> (2020). 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