Company: APM
Filing Date: 2025-07-15
Form Type: DRS
Source: 0001213900-25-063899
Chunk: 279

Company: Aptorum Group Ltd
Filing Date: 2025-07-15
Form: DRS
Chunk 279
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/AUC of 0.75/0.79. Both “progressor” and “non-progressor” groups included amyloid-positive                                
 and amyloid-negative participants as determined by CSF Aβ42. 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)                                                                                                                        |

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. |

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This analysis showed statistically significant
correlations of specific miRNA biomarker pairs with markers of AD, including in amyloid-positive and APOE4-carrier high-risk, clinically
relevant group. The correlations are significantly improved by sex-stratification of 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-carriers
by select miRNA classifiers. Separation of APOE4 carriers from non-carriers is improved in subgroups stratified by sex. The best separation
is observed within sex-stratified amyloid positive subgroup with AUC = 0.88 for males and AUC = 0.86 for females. Correlations between
other measured parameters, including p-tau181 and NfL, have also been determined.

The results generated in this study indicate that
levels of cell-free miRNA biomarker candidates have a strong potential to be used in combination with other AD markers and risk factors
to better characterize preclinical AD patients.

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