{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:54:33Z","timestamp":1791172473531,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational All"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The mannan\u2010conjugated birch pollen polymerised allergoid EP\u2010088_T502 has previously been shown to reduce allergic symptoms and anti\u2010allergic medication use during the birch pollen season. This confirmatory phase III trial aimed to evaluate the efficacy, safety, tolerability, and immunologic effects of EP\u2010088_T502 administered as eight subcutaneous injections over six pre\u2010seasonal treatment visits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this double\u2010blind, placebo\u2010controlled (DBPC) trial, 278 participants with birch pollen\u2013induced allergic rhinoconjunctivitis (ARC) received either placebo or a cumulative dose of 28,000 mannan therapeutic units (mTU) of EP\u2010088_T502. The primary efficacy endpoint was the combined symptom and medication score (CSMS) during the peak birch pollen season. Safety, tolerability, health\u2010related quality of life (QoL), and immunologic parameters were also assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the full analysis set (FAS), EP\u2010088_T502 significantly reduced the CSMS during the peak birch pollen season compared with placebo (mean absolute difference [MAD] \u22120.31; 95% confidence interval [CI], \u22120.56 to \u22120.05;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0169). In the per\u2010protocol (PP) and complete\u2010case sets, the corresponding MADs were \u22120.36 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.012) and \u22120.51 (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.013), respectively. Health\u2010related QoL improved by 20% in the EP\u2010088_T502 group compared with placebo during the peak season (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.005). EP\u2010088_T502 increased Bet v 1\u2010specific immunoglobulin G4 (IgG4) levels after treatment compared with placebo (6.4\u2010fold;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001). The Bet v 1\u2010specific immunoglobulin E (IgE)\/IgG4 ratio was reduced by 73% from baseline and by 69% compared with placebo (both\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001). Thirteen systemic allergic reactions occurred, including one grade III systemic reaction considered related to EP\u2010088_T502.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EP\u2010088_T502 significantly improved symptom and medication scores in participants with birch pollen\u2013induced ARC and induced a substantial Bet v 1\u2010specific IgG4 response. The 28,000 mTU regimen induced a substantial immunological response and showed an acceptable safety and tolerability profile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/clt2.70209","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:46:32Z","timestamp":1791171992000},"source":"Crossref","is-referenced-by-count":0,"title":["Short\u2010Course Subcutaneous Immunotherapy With Mannan\u2010Conjugated Birch Pollen Allergoids: Consistent Clinical and Immunological Improvements"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6461-8593","authenticated-orcid":false,"given":"Esther","family":"Raskopf","sequence":"first","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7410-9306","authenticated-orcid":false,"given":"Sofia","family":"Passamera","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute of Medical Statistics and Computational Biology University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2455-0192","authenticated-orcid":false,"given":"Ludger","family":"Klimek","sequence":"additional","affiliation":[{"name":"Center for Rhinology &amp; Allergology  Wiesbaden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4374-9639","authenticated-orcid":false,"given":"Oliver","family":"Pfaar","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Section of Rhinology and Allergy University Hospital Marburg Philipps\u2010Universit\u00e4t Marburg  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9323-6887","authenticated-orcid":false,"given":"Christian","family":"Neuhof","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5306-5412","authenticated-orcid":false,"given":"Anna","family":"Rybachuk","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5375-2853","authenticated-orcid":false,"given":"Nadine","family":"Katzke","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5516-2013","authenticated-orcid":false,"given":"Hacer","family":"Sahin","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0222-5954","authenticated-orcid":false,"given":"Silke","family":"Allekotte","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-810X","authenticated-orcid":false,"given":"Ralph","family":"M\u00f6sges","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"},{"name":"Faculty of Medicine Institute of Medical Statistics and Computational Biology University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5913-9208","authenticated-orcid":false,"given":"Laura","family":"Day","sequence":"additional","affiliation":[{"name":"ClinCompetence Cologne GmbH  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-5321","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Subiza","sequence":"additional","affiliation":[{"name":"Inmunotek S.L.  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