{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:58:15Z","timestamp":1790621895444,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>There is an unmet need for more effective therapies in inflammatory bowel disease (IBD). A single drug that blocks multiple distinct pathogenic pathways may offer therapeutic benefit superior to current monotherapies. PF\u201007261271, a bispecific antibody targeting both the p40 subunit of interleukin\u201012\/23 and tumour necrosis factor\u2010like cytokine 1A (TL1A), is being investigated as a potential new IBD therapy. This study evaluates the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of PF\u201007261271 in healthy participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This phase 1, randomized, double\u2010blind, placebo\u2010controlled study assessed single ascending doses (SAD; intravenous 30\u20131000\u2009mg) and multiple doses (MD; subcutaneous 300\u2009mg once every 4\u00a0weeks) of PF\u201007261271 in healthy adults. Safety, PK, immunogenicity and exploratory PD serum biomarkers (total soluble TL1A [sTL1A] and p40) were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty\u2010five participants were enrolled (Part A: SAD, N\u2009=\u200927; Part B: MD, N\u2009=\u20098). PF\u201007261271 was generally safe and well tolerated; all treatment\u2010emergent adverse events were mild\/moderate. Following peak serum concentration, there was a multi\u2010phase decline with a trend towards increased terminal half\u2010life at the higher doses. For the MD cohort, the estimated bioavailability of PF\u201007261271 administered subcutaneously was 48%. Dose\u2010dependent increases from baseline in serum total sTL1A and p40 levels were observed in participants receiving PF\u201007261271, demonstrating target engagement. There was no apparent impact of anti\u2010drug antibodies on safety, PK or PD parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PF\u201007261271 demonstrated p40 and TL1A target engagement and a favourable safety profile. Further studies are warranted to evaluate its safety and efficacy in patients with IBD.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>ClinicalTrials.gov:<\/jats:bold>\n                      NCT05536440.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70602","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T23:30:53Z","timestamp":1780529453000},"page":"3413-3423","source":"Crossref","is-referenced-by-count":0,"title":["A phase 1 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of PF\u201007261271 in healthy participants"],"prefix":"10.1002","volume":"92","author":[{"given":"Srividya","family":"Neelakantan","sequence":"first","affiliation":[{"name":"Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Banfield","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Hung","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sapone","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Parsons\u2010Rich","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Lee","sequence":"additional","affiliation":[{"name":"Pfizer Inc  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce G.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Peeva","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Vincent","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie M.","family":"Clerin","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25179751"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.765474"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102036.2011.04599.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i29.9675"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjaa050"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2022.1985999"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjae190.0031"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjae190.1022"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1636"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjae190.0039B"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2021.06.011"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468\u20101253(25)00129\u20103"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjae190.0039A"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1900750"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602773"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2147\/ITT.S282466"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000540421"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00583"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.37"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izab193"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2314076"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13237026"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16180"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2012.51"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.103017"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.09.078"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14187"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70602","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bcp.70602","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70602","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:55:21Z","timestamp":1790618121000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/bcp.70602"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70602","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]}}}