Bridging Discovery & Clinical Translation: InoKey™ for Biomarker-Driven Drug Development
Scientist
on
February 4, 2025
This blog post was written by Inoviv, a CRO that offers multiplexed & quantitative LC-MS proteomics with end-to-end support for drug discovery & development. Their services are available on Scientist.com.
While genomics and transcriptomics have transformed biomedical research, they do not always provide a complete picture of therapeutic response. Proteomics — measuring the dynamic state of proteins — bridges this gap, offering a real-time view of biological function and drug impact. Proteomics, the ultimate assessor of cell and tissue health, offers a crystal clear picture of a patient’s phenotype and provides substantial predictive potential. One critical gap remains: how do we bridge unbiased discovery proteomics findings and targeted proteomics assays to monitor dysregulated protein biomarkers with high precision and accuracy in the form of a clinically validated assay? InoKey™ has been developed to offer an elegant and comprehensive solution to the challenge of identifying novel protein biomarkers and translating those findings into a functional assay with clinical utility.
InoKey™: What is it and What Makes it Unique?
InoKey™ is a fully integrated discovery-to-targeted proteomics solution, designed to seamlessly bridge unbiased biomarker discovery with clinical assay development. From experimental design to validation, InoKey™ provides pharma and biotech teams with a streamlined, translatable biomarker strategy to de-risk drug development and improve clinical success (Figure 1). InoKey™ currently supports preclinical and clinical researchers globally, streamlining their biomarker strategy for monitoring drug mechanism-of-action, efficacy and patient stratification.
InoKey™ leverages advanced data-processing workflows, proprietary sample prep methodologies, and internally calibrated standards to deliver highly reproducible, high-sensitivity multiplex proteomics assays. With a linear dynamic range exceeding six orders of magnitude, InoKey™ provides absolute quantification from ng/mL down to pg/mL, enabling precise biomarker validation for clinical-scale applications. A separate IP-MS solution is also available for absolute quantification of even lower-level markers down to the pg/mL range in a multiplex format.
How InoKey™ Unraveled Critical Biomarker Signatures in SARS-CoV-2
How has InoKey™ Been Applied to COVID-19 Research?
A recent case study demonstrated how InoKey™ was applied in COVID-19 research, using a high-throughput LC-MS/MS workflow to stratify plasma proteomes and predict patient outcomes. The resulting MRM-based biomarker assay outperformed standard severity scoring models, offering a blueprint for how multiplexed biomarker panels can enhance precision medicine strategies in infectious disease and beyond (Figure 2). The resulting targeted MRM COVID-19 biomarker assay outperformed other severity score models and robustly predicted patient outcomes for a streamlined clinical treatment escalation strategy.
Method Overview
Discovery Proteomics Identified Clinically Actionable Biomarker Clusters Across Disease States
50 peptides corresponding to 30 plasma proteins were identified and selected through a discovery proteomics approach in plasma samples acquired from a deeply phenotyped COVID-19 patient cohort (n=139) (Figure 3). Biomarkers were selected based on different prognostic factors, including their association with the host response, such as inflammatory and innate immune response, complement cascade and coagulation.1,2
Building a Quantitative MRM-Based COVID-19 Biomarker Assay for Drug Development
Peptides determined from discovery proteomics studies informed the development of a MRM-based targeted COVID-19 biomarker test for use as a clinical assay.3 To investigate the assay’s performance and utility, the selected peptides’ performance was investigated, including intra- and inter-batch repeatability, quantification limit, linearity and accuracy (See Table).
A COVID-19 Biomarker Assay that Predicts Disease Severity and Patient Outcomes
Next, the chosen peptides were tested for their utility in classifying COVID-19 treatment escalation level, a proxy for disease severity.4 The markers displayed robust changes in abundance between the different patient WHO groups (Figure 4) and indeed classified patients into different groups (Figure 5A). The assay’s prognostic value was then established in a separate larger, longitudinal cohort. Based on the biomarker data, patients’ WHO grade predictions were in agreement with the actual treatment escalation. The targeted COVID-19 assay also outperformed other severity score models, strongly predicted COVID-19 patients’ outcomes and classified them according to their WHO grades (Figure 5B and 5C).
What Can We Conclude from the Results of this Case Study?
- Unbiased discovery proteomics revealed candidate COVID-19 disease severity biomarkers based on distinct patient clustering profiles
- The COVID-19 biomarkers demonstrated excellent analytical performance and therefore advanced for further development
- Using LC-MS/MS, an MRM-based targeted COVID-19 biomarker assay was analytically validated and developed for use in a clinical cohort
- The assay outperformed severity score models, strongly predicted patient outcomes, and classified them according to WHO grades
How is InoKey™ Shaping the Future of Proteomics?
InoKey™ represents a significant advancement in proteomics, offering a disease-agnostic platform that empowers researchers worldwide. By bridging the translational biomarker gap, it facilitates the development of clinically validated assays with unparalleled precision and utility.
Our disease-agnostic InoKey™ platform technology is now commercially available and supporting researchers globally to monitor drug mechanism-of-action, efficacy and patient stratification.
Bridge your translational biomarker gap with InoKey™. Select your panel and ship your sample, and we’ll handle the rest.
References
- High throughput LC-MS/MS stratification of plasma proteome response to SARS-CoV-2 infection. Lane, Catherine et al. Sciex technical note
- Demichev V, Tober-Lau P, Lemke O, et al. A time-resolved proteomic and prognostic map of COVID-19. Cell Syst. 2021
- A multiplex protein panel assay for severity prediction and outcome prognosis in patients with COVID-19: An observational multi-cohort study. Wang, Ziyue et al. eClinicalMedicine, Volume 49, 101495
- World Health Organization. R&D Blueprint Novel Coronavirus COVID-19 Therapeutic Trial Synopsis (WHO). 2020.