{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:18:39Z","timestamp":1790313519982,"version":"4.1.0"},"reference-count":25,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MBX Biosciences, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Hypoparathyroidism denotes parathyroid hormone (PTH) deficiency and impaired mineral metabolism. MBX 2109, a novel prodrug yielding a biologically active PTH peptide agonist (PTH[1-32], extended by a fatty acylated Lys33), is being developed as a long-acting, once-weekly PTH replacement therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Here, we report the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MBX 2109 in healthy volunteers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This phase 1, randomized, double-blind, placebo-controlled, multiple ascending-dose study (NCT05158335) enrolled healthy adults, who were randomly assigned 4:1 to receive MBX 2109 (200, 400, 600, and 900\u2005\u03bcg; n = 8) or placebo (n = 2) by subcutaneous administration once weekly for 4 doses (days 1, 8, 15, and 22). The primary end point was safety and tolerability. Key secondary end points were PK and PD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Overall, 40 participants (MBX 2109 n = 32, placebo n = 8) were randomly assigned (mean age, 43.3 years; 22.5% female). Treatment-emergent adverse events (TEAEs) occurred in 50% to 88% of MBX 2109 groups and in 25% of placebo participants. In the MBX 2109 groups, no severe or serious TEAEs were observed. Injection-site reaction was the most common treatment-related TEAE. The half-lives were 79 to 95\u2005hours for MBX 2109 and 184 to 213\u2005hours for the fatty-acylated biologically active PTH peptide, which showed dose- and time-dependent exposure increases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The sustained-action PTH prodrug MBX 2109 was well tolerated with no unexpected, off-target safety issues. The long half-life and flat exposure profile of MBX 2109's biologically active PTH agonist supports once-weekly administration. MBX 2109 doses were identified for future studies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae808","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T08:09:15Z","timestamp":1732262955000},"page":"940-950","source":"Crossref","is-referenced-by-count":14,"title":["MBX 2109, A Once-Weekly Parathyroid Hormone Replacement Therapy Prodrug: Phase 1, First-In-Human, Randomized Trial"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3946-2740","authenticated-orcid":false,"given":"Patricia","family":"Carney","sequence":"first","affiliation":[{"name":"Clinical Operations, MBX Biosciences Inc , Carmel, IN 46032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8925-5728","authenticated-orcid":false,"suffix":"Jr","given":"Gordon B","family":"Cutler","sequence":"additional","affiliation":[{"name":"Gordon Cutler Consultancy, LLC , Deltaville, VA 23043 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9244-0596","authenticated-orcid":false,"given":"Kristi","family":"Schneider","sequence":"additional","affiliation":[{"name":"Clinical Development, MBX Biosciences Inc , Carmel, IN 46032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1854-6393","authenticated-orcid":false,"given":"Fa","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Indiana University , Bloomington, IN 47405 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0220-4085","authenticated-orcid":false,"given":"Richard","family":"DiMarchi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Indiana University , Bloomington, IN 47405 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"issue":"6","key":"2025061606262554900_dgae808-B1","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1210\/clinem\/dgaa113","article-title":"Hypoparathyroidism","volume":"105","author":"Bilezikian","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2025061606262554900_dgae808-B2","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.ando.2023.04.001","article-title":"New directions in the treatment of hypoparathyroidism","volume":"84","author":"Hamny","year":"2023","journal-title":"Ann Endocrinol (Paris)"},{"issue":"2","key":"2025061606262554900_dgae808-B3","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s12020-023-03443-2","article-title":"Impairments in quality of life and predictors of symptom burden in patients with hypoparathyroidism: results from a population-based survey","volume":"82","author":"B\u00fcttner","year":"2023","journal-title":"Endocrine"},{"issue":"2","key":"2025061606262554900_dgae808-B4","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/cen.14128","article-title":"Burden of illness in not adequately controlled chronic hypoparathyroidism: findings from a 13-country patient and caregiver survey","volume":"92","author":"Siggelkow","year":"2020","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2025061606262554900_dgae808-B5","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.bone.2018.09.017","article-title":"Quality of life in hypoparathyroidism","volume":"120","author":"Vokes","year":"2019","journal-title":"Bone"},{"issue":"11","key":"2025061606262554900_dgae808-B6","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1002\/jbmr.1979","article-title":"Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study","volume":"28","author":"Underbjerg","year":"2013","journal-title":"J Bone Miner Res"},{"issue":"12","key":"2025061606262554900_dgae808-B7","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1002\/jbmr.4716","article-title":"Management of hypoparathyroidism","volume":"37","author":"Khan","year":"2022","journal-title":"J Bone Miner Res"},{"issue":"1","key":"2025061606262554900_dgae808-B8","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/jbmr.4726","article-title":"Efficacy and safety of parathyroid hormone replacement with TransCon PTH in hypoparathyroidism: 26-week results from the phase 3 PaTHway trial","volume":"38","author":"Khan","year":"2023","journal-title":"J Bone Miner Res"},{"issue":"10","key":"2025061606262554900_dgae808-B9","first-page":"3480","article-title":"A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1-34 in treatment of hypoparathyroidism","volume":"83","author":"Winer","year":"1998","journal-title":"J 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