LA MS DAY - PROGRAM

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Biography

Melissa joined Vividion’s proteomics team in 2020 as a Scientist I. She has progressed to lead the proteomics platform group operations. The team supports Early Discovery Sciences hit identification efforts and compound tractability through chemoproteomics screening and later-stage programs by measuring in vivo target engagement and protein PD responses. She is also leading the clinical target engagement assay development to support Vividion’s clinical trials and building out translational proteomics workflows.

Before coming to Vividion, Melissa completed a Clinical Chemistry Fellowship at UC San Diego under Dr. Robert Fitzgerald’s mentorship where she learned clinical assay validation and toxicology. She received her PhD in Cancer Biology from Moffitt Cancer Center/University of South Florida where she studied translational proteomics in Dr. John Koomen’s lab. She received her BS in Biology from California State University, Chico and is from the SF Bay Area.

Title of the talk: Chemoproteomic Discovery of RAS–PI3K Disruptors and Translation to a Clinical PI3K Target Engagement Assay 

The RAS–PI3Kα interaction is a critical oncogenic driver with attractive therapeutic vulnerability, yet efforts to target PI3K directly have been limited by toxicity and narrow therapeutic windows. Using Vividion’s targeted mass spectrometry–based chemoproteomics platform, we identified ligands to that engage Cys242 on p110a (the catalytic subunit of PI3Kα) that can disrupt the RAS-PI3Ka interaction. Lead inhibitors demonstrated robust in vivo target engagement (TE) and tumor growth inhibition in mouse xenograft models, validating PI3Kα C242 as a compelling target for clinical development.

To support clinical translation, we developed a PRM-based TE assay in peripheral blood leukocytes (PBLs) and transferred the assay to a GCLP lab. Validation demonstrated a lower limit of quantification of 2 amol/µg, robust linearity (R² = 0.991), and precision across operators and instruments (<20% CV). Reproducible quantification was achieved in non-small cell lung cancer patient samples collected from two different timepoints and up to 97% TE was measured in ex vivo treated PBLs.

This validated assay has been successfully applied in a Phase 1 clinical trial, demonstrating how chemoproteomic discovery can progress to a clinically deployable LC–MS assay, providing a quantitative framework for TE assessment, and in turn dose optimization, in clinical trials.

Biography

Dr. Jennifer Van Eyk, Ph.D, an international leader in clinical proteomics, is focused on democratizing personalized biomarkers and individualized therapies. She obtained her PhD from University of Alberta, and carried out post-doctoral fellowships in Heidelberg and Chicago before started her lab at Queen’s University, Kingston, Canada. She was recruited to Johns Hopkins University, Baltimore and then to Cedars-Sinai Medical Center, Los Angeles where she directs the inaugural Advanced Clinical BioSystems Research Institute. She is a Professor of Cardiology in the Smidt Heart Institute and holds the Erika Glazer Endowed Chair in Women’s Heart Disease. Her achievements include >425 articles, >26 patents, and numerous National and International research and leadership awards. 

Title of the talk: Precision Medicine: Proteomic Enablement of Biomarkers and Therapeutics 

Underlying precision medicine is the concept that an individual’s Omic signature, including the proteome, will provide a physician with a clinically actionable diagnosis and a subsequent mechanistic therapeutic route. This requires: i) an array of mechanistically defined therapies for diverse disease states, and ii) high-resolution diagnostic approaches capable of identifying which therapy, or therapeutic combination, will be most effective for a specific patient.

Proteomics has played a role in the discovery, and now, it is time to move into implementation. We will focus on how technology is now allowing scalable, robust automated protein measurements that enable translation. We illustrate this with our Molecular Twin program, where multi-omic data was used to determine an individual’s molecular phenotype in context to cancer. By computationally aligning a patient’s molecular profile with those of others, we identify their “molecular twin,” revealing shared signaling networks, pathway perturbations, and therapeutic response patterns in plasma. Equally critical, precision medicine requires validated clinical interventions. We will discuss how proteomics has helped to shape the use of a new drug class for which a single dose immediately following a heart attack is sufficient to stop heart remodeling and death, and how its differential effect at the single-cell level can have profound implications.