No treatment effects on body weight were noted. No treatment -related and/or toxicologically significant effects for any clinical chemistry parameters evaluated were noted during any of the studies. All hematology parameters, red blood cell counts, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration remained normal. Toxicology of the PDS0101 clinical formulation (6- peptide HPVmix and ImmunoMAPKRDOTAP) was evaluated in humanized transgenic mice. The transgenic mice expressed the human HLA -A2 antigen recognition and presentation molecule, and their antigen presenting cells were therefore capable of recognizing and responding to the HPV A2 epitope human peptide antigens in the drug formulation. Similar to toxicology studies in rats and monkeys 12 Abbreviated Title: Combo Immunotx in HPV Cancers Version Date: 05.12.2023 with the prototype drug formulation, few clinically relevant toxicological effects were observed at any dose level in the transgenic humanized mice. However, for the clinical PDS0101 formulation mean hematocrit was decreased in the low R -DOTAP + HPVmix and high R -DOTAP + HPV mix groups by approximately 3% and 5%, respectively; and although minimal, may be related to treatment. No treatment -related toxicological findings were observed during gross necropsy. Microscopic histopathologic findings (minimal fibrosis) considered related to treatment with the test article were limited to the skin at the injection site in 3 out of 8 in the high R -DOTAP + HPV mix group only. In 2014-2016, a Phase I/IIA human clinical trial was performed at 3 sites in the US in 12 subjects with high- risk HPV infection and biopsy- proven cervical intraepithelial neoplasia (CIN1) to study the safety and immunogenicity of PDS0101.The study initiated with Cohort 1 and progressed through Cohort 3, with each subsequent cohort receiving a higher dose of PDS0101 (i.e., 1.0, 3.0, and 10.0 mg R -DOTAP); 3 in Cohort 1 (1- mg R -DOTAP dose), 3 in Cohort 2 (3 mg R -DOTAP dose), and 6 in Cohort 3 (10- mg RDOTAP dos e). Successive cohorts received a constant dose of 2.4 mg HPV -16 E6 and E7 peptides (400 μg/peptide) with 1 of 3 escalating doses of R -DOTAP. All subjects received 3 doses of vaccine given SC, approximately 21 days apart. 10/12 subjects had a positive vaccine -induced response (a ≥3- fold increase over baseline at ≥1 of the 4 post - vaccination visits by either the IFN -γ or granzyme B ELISpot assays, with background counts subtracted). Individual subject results from both the I FN-γ and the granzyme B assays showed that all doses of RDOTAP were effective in inducing HPV -specific T -cell responses ( Figure 2A). IFN - γ (all T -cells) and the granzyme B (CD8+ T -cells) responses were elicited in both HPV -16+ and HPV-16- subjects, and in subjects with various HLA types. Administration of PDS0101 was also well tolerated.