Company: MDCXW
Filing Date: 2025-04-04
Form Type: POS AM
Source: 0001062993-25-007073
Chunk: 104

Company: Medicus Pharma Ltd.
Filing Date: 2025-04-04
Form: POS AM
Chunk 104
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 and minipig pharmacokinetic data, we concluded that human systemic exposure to doxorubicin is unlikely through the application of the D-MNA.

Analytical Methods and Validation

A bioanalytical method was validated for the determination of doxorubicin in Yucatan minipig plasma ("K2EDTA") by liquid chromatography tandem mass spectrometry ("LC-MS/MS") at a dynamic range of 0.250 - 50.0 ng/ml. The analyte is light sensitive and exposure to direct light was minimized during extraction and analysis. Doxorubicin-13C,d3 was used as the internal standard.

A summary of the validation data for the analyte is presented in the table below.

Summary of Validation Data from LC-MS/MS Study

| Analyte                                                     | Doxorubicin                      |                                                                  |
| Matrix                                                      | Yucatan Mini Pig Plasma (K2EDTA) |                                                                  |
| Analytical Procedure                                        | LC-MS/MS                         |                                                                  |
| Assay Aliquot Volume                                        | 50 µl                            |                                                                  |
| Sample Preparation                                          | Protein Precipitation            |                                                                  |
| Assay Range                                                 | 0.250 - 50.0 ng/ml               |                                                                  |
| Regression                                                  | Linear (1/x2)                    |                                                                  |
| Selectivity                                                 | 6 of 6 lots within acceptance    | ≤ 20% of mean LLOQ, ≥90% of individual lots free of interference |
| Injector Carryover                                          | Not Significant                  | ≤20% of mean LLOQ                                                |
| Validation Batch Acceptance (Acceptable/Total Primary Runs) |                                  | 4/4                                                              |

The toxicity of doxorubicin hydrochloride has previously been evaluated and reported in standard preclinical toxicology models. More important, the toxicity profile of parenteral doxorubicin in humans at doses cytotoxic to cancers has been well established and recounted in the Investigator Brochure for D-MNA Patch (September 4, 2018).

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We have not conducted any formal safety pharmacology studies. However, selected parameters that are typically collected in CNS and respiratory safety pharmacology were collected in the form of clinical observations in the below-listed toxicology studies. In addition, electrocardiograms were recorded in a pivotal toxicology study in minipigs and were evaluated by a board-certified veterinary cardiologist.

We have completed three GLP-com