Company: MDCXW
Filing Date: 2025-04-25
Form Type: DRS
Source: 0001062993-25-007956
Chunk: 110

Company: Medicus Pharma Ltd.
Filing Date: 2025-04-25
Form: DRS
Chunk 110
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 5 control group, all array-treated groups showed doxorubicin plasma levels below the lower limit of quantitation ("LLOQ"), which for this LC-MS/MS method was 0.25 ng/ml. The study sponsor concluded that in the minipig model there was no measurable systemic exposure to doxorubicin when administered by the Sponsor's tip-loaded, dissolvable microneedle array.

Based on the mice 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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