Company: APM
Filing Date: 2025-07-15
Form Type: DRS
Source: 0001213900-25-063899
Chunk: 265

Company: Aptorum Group Ltd
Filing Date: 2025-07-15
Form: DRS
Chunk 265
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 and use synthetic controls to develop a working assay. |
| Step 2: | Analytical Validation Study. In this step DiamiR’s goal is to determine key analytical validation metrics, as required by CLIA guidelines, for the pipeline product. Using synthetic controls and/or call lines and clinical samples DiamiR establishes:                                                                                                                                                                                                                       |

| ● | Accuracy                         |
| ● | Precision                        |
| ● | Reproducibility; and             |
| ● | Reportable ranges for the assay. |

DiamiR will also run the assay by multiple
operators over different days to establish the test’s inter and intra-run reproducibility metrics.

Test optimization refers to finalizing
the testing parameters and locking in the Standard Operating Procedures (SOPs) and finalizing algorithms used to analyze the raw data
from DiamiR’s runs.

| Step 3: | Clinical Validation Study. In this step, the tests’ performance characteristics will be determined using clinical samples with known outcomes. By comparing DiamiR’s test results with clinical outcomes, DiamiR determined the assays: |

| ● | Clinical Accuracy |

| ■ | Area Under the Curve (AUC, a measure of difference between diseased and non-diseased samples) |

| ● | Sensitivity (a measure of Test’s ability to designate an individual with disease as positive)                |
| ● | Specificity (a measure of Test’s ability to designate an individual who does not have a disease as negative) |
| ● | Negative Predictive Value (NPV)                                                                              |
| ● | Positive Predictive Value (PPV)                                                                              |

A test with robust Clinical Validation
results can be made commercially available.

Once a test has successfully completed all three
steps noted above, it can be commercialized. However, a producer/manufacturer may decide not to move to commercialize the test until it
receives sufficient reimbursement coverage.

Validating a test to ensure it is ready for launch
requires clinical evidence and FDA clearance; commercializing a product requires reimbursement from CMS/Medicare and private insurance
companies, as tests that are not reimbursed most likely will not gain uptake in the marketplace. To garner coverage and have a test deemed
medically necessary, payors will typically require additional studies, including Clinical Utility studies aimed at demonstrating how a
test changes patients’ treatment and/or physician behavior. For example, a test with high clinical utility may prevent unnecessary
surgeries or help physicians choose the right therapeutic regimen for or recommend an important lifestyle change to a