Acrivon Predictive Precision Proteomics (AP3) – Transcending Limitations of Genetics-Based Precision Medicine 

Talk by Magnus Jakobsson, Ph.D., Director, Head of Proteomics at Acrivon Therapeutics 

Acrivon discovers and develops precision medicines through its proprietary Generative Phosphoproteomics AP3 platform, designed to overcome the limitations of genetics-based precision medicine.
AP3 is engineered to measure compound-specific effects on the entire cellular protein signaling network and uncover drug-induced resistance mechanisms in an unbiased manner, while agnostic to both drug modality and disease. These distinctive capabilities enable AP3’s direct application for drug design optimization based on desirable intracellular pathway effects, identification of rational drug combinations, and creation of drug-specific OncoSignature companion diagnostics that are used to prospectively identify patient responders in our ongoing registrational intent Phase 2b trial.

Benchmark of enrichment and depletion methods for quantitative plasma proteomics and their correlation to clinical routine measurement. 

Talk by Anders H. Kverneland, PhD., MD at Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital

In recent years several preparatory techniques for enrichment or depletion for MS proteomics have been developed to overcome the extreme dynamic range in plasma. In this study we test and benchmark several workflows with intra- and inter-sample comparisons.  In addition we test the correlaton to clinical routine protein analyte measurements performed at the hospital laboratory.

High throughput plasma proteomics empowers population-based studies

Talk by Lili Niu, Junior Principal Investigator at Institute of Chemical Biology, Shenzhen Bay Laboratory

Mass spectrometry (MS)-based proteomics has entered the era of high throughput, with current plasma proteomics detecting over 1,000 proteins in a single-shot 21-minute gradient and several times more when combined with enrichment or depletion strategies. In our previous work, we identified promising biomarker panels for chronic liver disease that outperformed or matched existing clinical tests even at a modest depth of 400 proteins. This finding suggests that, for certain disease models, streamlined neat plasma proteomics remains a cost-effective, highly robust, and attractive analytical option.

In our recent study involving more than 6,400 individuals, we established an end-to-end high-throughput sample preparation pipeline capable of processing 1,152 neat plasma samples per day. A 200 samples-per-day (SPD) LC–MS/MS workflow on the Evosep Eno system coupled online to an Orbitrap Astral mass spectrometer achieved robust quantification of more than 400 proteins per sample. In this talk, I will share our considerations for scaling up sample preparation, optimizing data acquisition schemes, and evaluating analytical performance, and highlight some initial biological insights emerging from this large-scale dataset.