Company: MDCXW
Filing Date: 2025-09-11
Form Type: DRS
Source: 0001062993-25-015568
Chunk: 128

Company: Medicus Pharma Ltd.
Filing Date: 2025-09-11
Form: DRS
Chunk 128
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1)Dosing volume for Group 5 was 1 ml/kg (doxorubicin hydrocholoride 2 mg/ml). NA = Not Applicable IV = Intravenous

Blood collections for toxicokinetic evaluation were conducted on Days 1 and 14 post dose administration (post-30 mins application for Groups 1-4) for all groups.

Excluding the group 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.

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| CONFIDENTIAL TREATMENT REQUESTED BY MEDICUS PHARMA LTD. 
 PURSUANT TO 17 C.F.R. SECTION 200.83                    |

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%