{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:28:22Z","timestamp":1786548502010,"version":"build-2736575974"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH Graduate Training at the Biology\u2013Chemistry Interface Grant","award":["T32-GM132061"],"award-info":[{"award-number":["T32-GM132061"]}]},{"name":"NIH Graduate Training at the Biology\u2013Chemistry Interface Grant","award":["R01-AG082273"],"award-info":[{"award-number":["R01-AG082273"]}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"WuXi Biologics USA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>LABL-Fc-MOGR5 is a bifunctional peptide inhibitor designed to modulate immune responses in multiple sclerosis, including primary progressive multiple sclerosis. Although therapeutically promising, its development has been hindered by poor physical stability, particularly rapid precipitation under standard formulation conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A high-throughput, multi-phase formulation strategy was implemented to improve conformational and colloidal stability. An initial Phase 1 evaluation used intrinsic fluorescence differential scanning fluorometry and polyethylene glycol (PEG) solubility assays to screen 96 formulations spanning a range of pH values, buffer systems, and excipients. Then, a Phase 2 study applied a definitive screening design to evaluate key formulation variables\u2014including buffer type, excipients, and surfactant concentration\u2014at reduced protein concentration in 96-well plates. A final Phase 3 study compared the lead formulation from Phase 2 with the control formulation at higher protein concentration in glass vials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The Phase 1 study revealed pronounced sensitivity of LABL-Fc-MOGR5 to pH and ionic strength. Divalent anionic buffers (e.g. citrate, succinate) and excipients such as sucrose and hydroxypropyl-\u03b2-cyclodextrin substantially reduced aggregation propensity. In the Phase 2 study, an optimized formulation was identified\u201410\u00a0mM sodium acetate, pH\u00a05.3, 125\u00a0mM sucrose, 150\u00a0mM HBP-LB-\u03b2CD, and 0.025% polysorbate 80\u2014based on statistical modeling. This formulation demonstrated markedly improved resistance to aggregation, fragmentation, and subvisible particle formation under accelerated stress relative to the control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This work underscores the value of excipient selection and rational design of experiments in stabilizing complex fusion proteins. The optimized formulation provides a significantly enhanced stability profile and supports further development of LABL-Fc-MOGR5 toward clinical evaluation for primary progressive multiple sclerosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/abt\/tbag005","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:19:55Z","timestamp":1771924795000},"page":"215-229","source":"Crossref","is-referenced-by-count":0,"title":["Preventing physical and chemical degradation of the LABL-Fc-MOGR5, a bifunctional peptide inhibitor, with formulation development approaches"],"prefix":"10.1093","volume":"9","author":[{"given":"Lun","family":"Xin","sequence":"first","affiliation":[{"name":"BioDev Department, WuXi Biologics USA , Cranbury, NJ 08512,","place":["United States"]},{"name":"Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, KS 66047 ,","place":["United 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