{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T04:40:38Z","timestamp":1776660038712,"version":"3.51.2"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"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":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Model\u2010informed drug development (MIDD) has an important role to play at various stages of drug development. In this case study, the application of MIDD in the early clinical development of a small\u2010molecule inhibitor of sickle hemoglobin (Hb) polymerization is highlighted. Starting from the setting of quantitative criteria, to using a combination of PKPD and semi\u2010mechanistic RBC modeling, and key biomarker analysis, based on data from a healthy participant first\u2010in\u2010human (FIH) study and historical data, we chart the strategic approaches planned and taken to inform decisions for the program, and the role of cross\u2010functional collaboration. Based on the projections from the PKPD and semi\u2010mechanistic RBC models, and key biomarker results from healthy participants, an informed decision was made to not proceed to a Phase 1b study in sickle cell disease (SCD) patients, underscoring the value of MIDD in early drug development decision making.<\/jats:p>","DOI":"10.1002\/psp4.70238","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T04:25:51Z","timestamp":1774671951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Utilization of Model\u2010Informed Drug Development in Early Clinical Development: Case Study of a Hb Modulator for Treatment of Sickle Cell Disease"],"prefix":"10.1002","volume":"15","author":[{"given":"Chay Ngee","family":"Lim","sequence":"first","affiliation":[{"name":"Pfizer Inc  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nessy","family":"Tania","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7225-1317","authenticated-orcid":false,"given":"Satyaprakash","family":"Nayak","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Rybin","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jatin","family":"Narula","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Arkin","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61029-X"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2006.07.001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1510865"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05332.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1996.d01-1744.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1993.tb04160.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1984.tb10775.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903212"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13896"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107190"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/03630268508997038"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014\u20105793(87)80509\u20104"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/03630260600755666"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.4.5990.200"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010002\u20100447\u20106"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01518"},{"key":"e_1_2_10_18_1","unstructured":"\u201cMulticenter Study of Hydroxyurea (MSH) [Dataset] \u201dhttps:\/\/biolincc.nhlbi.nih.gov\/studies\/MSH\/."},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505183322001"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12063"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3744"}],"container-title":["CPT: Pharmacometrics &amp; 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