Company: APM
Filing Date: 2025-07-15
Form Type: DRS
Source: 0001213900-25-063899
Chunk: 223

Company: Aptorum Group Ltd
Filing Date: 2025-07-15
Form: DRS
Chunk 223
---
 substantial time and financial resources.

<div align='center'>114</div>

The principal steps required
for drug approval in Canada is as follows:

Preclinical Toxicology Studies

Non-clinical studies
are conducted in vitroand in animals to evaluate pharmacokinetics, metabolism and possible toxic effects to provide
evidence of the safety of the drug candidate prior to its administration to humans in clinical studies and throughout development. Such
studies are conducted in accordance with applicable laws and GLP.

Initiation of Human Testing

In Canada, the process of
conducting clinical trials with a new drug cannot begin until we have received a NOL (No objection Letter) from Health Canada, typically
within 30 days (during Covid the 30 days extended to 45 days) of a CTA submission. Similar regulations apply in Canada to a CTA as to
an IND in the United States. Once approved, two key factors influencing the rate of progression of clinical trials are the rate at which
patients can be enrolled to participate in the research program and whether effective treatments are currently available for the disease
that the drug is intended to treat. Patient enrollment is largely dependent upon the incidence and severity of the disease, the treatments
available and the potential side effects of the drug to be tested and any restrictions for enrollment that may be imposed by regulatory
agencies.

Clinical Trials

Similar regulations apply
in Canada regarding clinical trials as in the United States. In Canada, Research Ethics Boards, or REBs, instead of IRBs, are used to
review and approve clinical trial plans. Clinical trials involve the administration of an investigational new drug to human subjects under
the supervision of qualified investigators in accordance with current Good Clinical Practices, or cGCP, requirements, which include review
and approval by REBs. Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, the trial
procedures, the parameters to be used in monitoring safety and the efficacy criteria to be evaluated and a statistical analysis plan.
Human clinical trials are typically conducted in three sequential phases, as discussed above in similar context to government regulation
in the United States.

The manufacture of investigational
drugs for the conduct of human clinical trials is subject to current Good Manufacturing Practice, or cGMP, requirements. Investigational
drugs and active pharmaceutical ingredients imported into Canada are also subject to regulation by Health Canada relating to their labeling
and distribution. Post authorization requirements include reporting of serious adverse events and clinical trial site inspection program.
Phase