ProteoModels Efficacy Testing

Correlating Baseline Biology to Therapeutic Response

Traditional cell-line profiling screens often lack clinical translation because the models do not mirror the proteomic heterogeneity found in clinical patient tumors.

Yatiri Bio bridges this preclinical gap using ProteoModels. We isolate cellular inputs from patient tumor cohorts, cultivating them under low-passage conditions to preserve primary characteristics. Prior to compound screening, each model is mapped using unbiased mass spectrometry to quantify baseline protein expression and kinase phosphorylation matrices.

When biopharma partners submit compounds for sensitivity screening (measuring IC50, GI50, and apoptotic induction), our computational systems automatically correlate response profiles against baseline proteomics, mapping the exact molecular signatures that dictate therapeutic sensitivity or resistance.

Core Model Focus: AML & Ovarian Cancers

We focus our primary model acquisition on indications characterized by high clinical failure rates and molecular complexity:

• Acute Myeloid Leukemia (AML): Ex-vivo models covering FLT3-ITD, IDH1/2 mutant, and TP53 mutant backgrounds. Ideal for testing targeted inhibitors and combination runs (such as Venetoclax sensitivity studies).
• Ovarian Cancer: Ex-vivo organoid lines representing high-grade serous ovarian cancer (HGSOC), including homologous recombination deficient (HRD) and proficient backgrounds.

Screening Methodology

Our San Diego laboratory incorporates automated liquid handling systems to execute high-throughput dose-response runs. Cells are seeded in multi-well microplates and treated with up to 10-point concentration curves. Efficacy measurements include:

• Cell Viability (quantified via ATP luminescence or fluorogenic dye assays).
• Apoptotic Induction (quantified via caspase-3/7 cleavage activation).
• Post-treatment target modulation (quantified via capillary Western or mass-spec phosphoproteomics).