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In this disorder, hyperabsorption of 3\u20135\u00a0mg of iron per day cannot be counterbalanced by the typical passive elimination of 1\u20132\u00a0mg of iron each day into the feces by the shedding of enterocytes. Therefore, the current standard of care for most HH individuals who develop iron overload is to undergo systemic iron reduction with induction-phase phlebotomy therapy followed by long-term maintenance phlebotomy therapy. Unfortunately, long-term compliance with a regular phlebotomy regimen is less than 25%\u00a0in some clinical settings. BBI-001 is a non-absorbed, oral therapeutic that binds dietary iron in the gut, preventing absorption and promoting iron elimination in the feces. The safety and efficacy of BBI-001 was confirmed in a single ascending dose, double-blind, Phase 1b clinical trial NCT05238207 (14\/02\/2022) in patients with iron deficiency. No treatment-related adverse events occurred for single doses of up to 2000\u00a0mg of BBI-001. The study also established proof-of-mechanism since BBI-001 significantly reduced the absorption of iron isotopes from breakfast meals compared to placebo. BBI-001 was most effective in subjects who hyperabsorbed iron (&gt;\u20093\u00a0mg) on placebo, suggesting an ability to normalize iron absorption in at-risk patients. This study supports the further evaluation of BBI-001 as a safe pharmaceutical alternative to lifelong therapeutic phlebotomy.<\/jats:p>","DOI":"10.1038\/s41598-025-01421-4","type":"journal-article","created":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T12:37:38Z","timestamp":1747485458000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A phase 1b randomised clinical trial evaluating BBI-001, a non-absorbed oral therapeutic for the treatment of iron overload"],"prefix":"10.1038","volume":"15","author":[{"given":"Curtis","family":"Scribner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Cope","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John K.","family":"Olynyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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Hemochromatosis. https:\/\/www.hopkinsmedicine.org\/health\/conditions-and-diseases\/hemochromatosis (2023)."},{"key":"1421_CR4","doi-asserted-by":"publisher","first-page":"18016","DOI":"10.1038\/nrdp.2018.16","volume":"4","author":"P Brissot","year":"2018","unstructured":"Brissot, P. et al. Haemochromatosis. Nat. Rev. Dis. Prim. 4, 18016 (2018).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"1421_CR5","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1111\/j.1749-6632.1988.tb55510.x","volume":"526","author":"G Strohmeyer","year":"1988","unstructured":"Strohmeyer, G., Niederau, C. & Stremmel, W. Survival and causes of death in hemochromatosis. Ann. N York Acad. Sci. 526, 245\u2013257 (1988).","journal-title":"Ann. N York Acad. Sci."},{"key":"1421_CR6","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/0016-5085(91)90013-B","volume":"101","author":"PC Adams","year":"1991","unstructured":"Adams, P. C., Speechley, M. & Kertesz, A. E. 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It now reads: \u201cWith gratitude and enthusiasm, the authors would like to acknowledge those who enabled the completion of this trial through the nonclinical development of BBI-001, including Paddy Shivanand and Willi Stahl for drug substance manufacturing and qualification, Colleen Johnson for the execution of the nonclinical toxicology program, Cara Casseday and Yuri Stasiv for management of clinical operations, Steve Smith for contributions to data analysis, and Michael Riley for leadership and company operations. We also gratefully acknowledge the provision of isotopic iron and advice for isotope quantitation from the laboratory of Diego Moretti at Fernfachhochschule Schweiz.\"","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All methods were carried out in accordance with relevant guidelines and regulations of the Australian Therapeutic Goods Administration (TGA). All experimental protocols were approved by the Bellberry Human Research Ethics Committee in consultation with the TGA. Studies were conducted under informed consent for all subjects and\/or their legal guardians.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and accordance"}},{"value":"Authors CS, JDG, and CB hold ownership interests in Bond Biosciences, Inc. All the remaining authors declare no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17210"}}