Company: APM
Filing Date: 2025-10-06
Form Type: S-4
Source: 0001213900-25-096656
Chunk: 363

Company: Aptorum Group Ltd
Filing Date: 2025-10-06
Form: S-4
Chunk 363
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ICTION OF PROGRESSION IN SEX-STRATIFIED GROUPS

| In a study conducted with plasma samples collected at Washington University, St Louis, MO, miRNA pairs differentiated asymptomatic study participants, with CDR 0 at the time of blood collection, who would progress to MCI (“progressors”, n=42, on average 6 years) from those who would remain cognitively normal (“non-progressors”, n=42) with an accuracy/AUC of 0.75/0.79. Both “progressor” and “non-progressor” groups included amyloid-positive and amyloid-negative participants as determined by CSF Aβ. Considering sex as a biological variable increased the accuracy/AUC to 0.85/0.88 (male) and 0.84/0.86 (female). 
 (10th Clinical Trials on Alzheimer’s Disease (CTAD), 2017, Boston, MA, poster presentation)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           |

206

DEFINING CLINICALLY RELEVANT PATIENT GROUPS

| The main objective of this study was to evaluate correlations and associations between the 24 miRNAs constituting CogniMIR® panel of miRNA biomarkers, and demographic and clinical factors known to be associated with AD, such as age, sex, amyloid status, APOE genotype, p-tau and neurofilament light (NfL), in 299 plasma samples collected during screening for the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) prevention study. |

This analysis showed statistically significant correlations of specific miRNA biomarker pairs with markers of AD, including in amyloid -positiveand APOE4 -carrierhigh -risk, clinically relevant group. The correlations are significantly improved by sex -stratificationof study participants. miRNA pairs and SUVR correlation plots in amyloid positive/negative, APOE4 carriers/non -carriers, and male/female subgroups demonstrate strong correlations with r = 0.33 to 0.59; p = 0.034 to < 0.001. In amyloid positive/negative subgroup, APOE4 carriers are effectively separated from APOE4 non -carriersby select miRNA classifiers. Separation of APOE4 carriers from non -carriersis improved in subgroups stratified by sex. The best separation is observed within sex -stratifiedamyloid positive subgroup with AUC =