Corrigendum: AN EXPLORATORY ANALYSIS OF BEZISTERIM TREATMENT ASSOCIATED WITH DECREASED BIOLOGICAL AGE ACCELERATION, AND IMPROVED CLINICAL MEASURE AND BIOMARKER CHANGES IN MILD-TO-MODERATE PROBABLE ALZHEIMER'S DISEASE

Christopher L Reading^1*Jiayan Yan²Marcia Testa³Donald C. Simonson⁴Hira Javaid⁵Lisa Schmunk⁵Daniel E. Martin-Herranz⁵Robert Brooke⁶Juozas Gordevicius⁶Jeffrey Yangang Zhang⁷Harvey Yuan⁷Clarence Ahlem²Lixia Wang²Penelope Markham²Nily Osman²Stephen O'Quinn²Joseph Palumbo²

• ¹BioVie Pharma, Carson City, United States
• ²BioVie Inc., Carson City, United States
• ³Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, United States
• ⁴Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
• ⁵Hurdle.bio/Chronomics Ltd., London, United Kingdom
• ⁶Epigenetic Clock Development Foundation, Torrance, United States
• ⁷Princeton Pharmatech, Princeton, United States

this does not change the scientific conclusions of the article in any way. The original article has been updated. **TABLE 4. Correlations between exploratory biomarkers and neurological assessments (perprotocol population). Associations were explored between eight biomarker measures and seven neurological assessments for placebo and bezisterim subjects. Pearson correlations with p < 0.05 (not corrected for multiple testing) are provided in bold in the table. Correlations of interest are highlighted in orange (positive) or blue (negative), see the text for details. Correlation analyses are from single laboratory or clinical measurements at the completion visit. Laboratory values are from single samples obtained from single blood draws at completion, but from different tubes depending on the test performed. pTau217, NfL, and GFAP data were from duplicate samples from the same tube for each subject. For Placebo, n = 26 except for SBC dAge correlations (n = 16); for bezisterim, n = 24 except for SBC dAge correlations (n = 17).** In the original article, there was a mistake in **Figure 7. Heat map of exploratory biomarker correlations with neurological assessments (per-protocol population)** as published. **Errors were detected in the signs, correlations, and P values used during the heat map formation. We removed the heat maps to eliminate the visualization of the errors, corrected the data in the remaining table as shown in tracked changes below, rearranged the table to facilitate side-by-side between-group comparisons, and renamed the display item to In the original article, there was an error. **The results summary for the data that were shown in Figure 7 paralleled the errors that were noted above for ** Seven AD biomarkers correlated with neurological assessments at study completion (Table 4). The table displays marked differences between the correlations for placebo subjects and bezisterim subjects. For placebo subjects, increases in GFAP were associated with a decline in cognitive and functional assessments (increased GST, CDR-SB, ADCOMS, ADAS-Cog 12; decreased MMSE). Increases in pTau217 were associated with decline (GST, ADCOMS, ADAS-Cog12, CGIC). Increased CRP levels were associated with a decline in ADL. RANTES levels were associated with a decline in CDR SB. There were no associations with SBC dAge for placebo subjects.For bezisterim subjects, decreased pTau was associated with improved ADL. Cholesterol (which was decreased in bezisterim subjects) was correlated with the decreases in GST and Cog12 and the increased MMSE scores. Improvements in GST, CDR SB, ADCOMS, Cog12, and ADL in bezisterim subjects were correlated with decreased NfL levels. For bezisterim subjects, RANTES was positively associated with improvements in GST, CDR SB, ADCOMS, ** The exploratory analyses of primary and secondary neurological endpoints and biomarkers suggest that bezisterim treatment may improve neurological measures in AD, correlating with changes in clinical parameters and epigenetic and biological markers related to metabolism, oxidative stress, inflammation, aging, and dementia. Bezisterim treatment appeared to alter exploratory correlations compared to those found in placebo participants. While the directions of correlations observed in placebo-group participants were consistent with expectations for AD, directions of many of the correlations observed in bezisterim participants were consistent with the hypothesis that bezisterim-mediated improvements in inflammation driven by metabolic dysregulation might be associated with neurological improvements. For example, in placebo subjects, progression associated biomarkers, including GFAP, pTau217, and CRP levels at completion, were associated with cognitive and functional decline (as measured by GST, CDR-SB, ADCOMS, ADAS-Cog12, CGIC, ADL, and MMSE) as expected. For bezisterim subjects, however, the improvements relative to placebo in cognitive functional markers were associated with decreased cholesterol, NfL, SBC dAge, and increased RANTES.RANTES is a chemokine reported to have contradictory roles, both neurodegenerative and neuroprotective, in AD (Li and Zhu, 2019;Ma et al., 2023) disease progression. While neither placebo nor bezisterim participants had significant correlations for these associations at baseline, at 7 months, placebo RANTES correlated with CDR SB decline, while the bezisterim participants' RANTES levels correlated with improvements in the GST, CDR-SB, ADCOMS, Cog12, and MMSE endpoints. These results are compatible with the hypothesis that RANTES might contribute to neurodegeneration over time, and that bezisterim treatment might alter regulatory effects of RANTES on cognitive assessments.** The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.