Proteomics-driven insights for pharmaceutical development

Publication highlights April 2026

Escalating costs and increasing demands from regulatory authorities for a more precision medicine-based approach to drug development are substantial challenges for the pharmaceutical industry. Olink’s PEA technology is increasingly used to identify new drug targets and analyze samples from clinical trials to stratify patient populations, predict responses, and provide insights into the biology of disease and drug modes of action. Here we highlight some recent outstanding studies that illustrate the key role of protein biomarker research in the discovery and development of new therapies.

Multiomic profiling of atherosclerotic instability

Atherosclerotic cardiovascular disease (ASCVD) remains a major global health issue, associated with a high degree of mortality and morbidity from myocardial infarction (MI) or ischemic stroke (IS). Patients with unstable, symptomatic atherosclerotic disease have a >10-fold higher annual risk of stroke compared to those with stable, asymptomatic disease.

Scientists from the Karolinska Institute in Stockholm and Novo Nordisk A/S in Denmark carried out an innovative study of carotid stenosis patients, integrating multiomic data obtained both locally from atherosclerotic plaques and from the peripheral circulation. Combining transcriptomics, metabolomics, and proteomics measured using five Olink® Target 96 panels, they employed the Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) machine learning method to derive molecular signatures associated with atherosclerotic plaque stability, CVD outcomes, and therapeutic responses.

Proteomics identified 15 proteins significantly associated with atherosclerotic disease symptomatology that overlapped in plasma taken from both the peripheral circulation and adjacent to plaque lesions.

• These included both well-established atherosclerosis markers and more novel proteins like ICOSLG, PCOLCE, FUT5, CCL20, CA6, & KITLG.
• Chemokine signaling and cytokine-receptor interaction pathways were upregulated in both sample types, while the IL-17 pathway was specifically enriched only locally.

Integrated multiomics identified distinct symptomatology-associated profiles of transcripts, metabolites and proteins that varied when analyzed peripherally, at the disease site, or at the intersection of these compartments.

• FABP4, IL6, Bilirubin and Sphingomyelin were the most prominent analytes peripherally; F11, ANGPTL3, ICOSLG, ITGB1 and Sphingomyelin locally; and FABP4, C1R, IL6, Bilirubin and Sphingomyelin were prominent at the intersection.
• Pathway analysis highlighted coagulation, necroptosis, inflammation, and cholesterol metabolism as key determinants of symptomatology.

Higher peripheral plasma protein levels of ANGPTL3 were significantly associated with more frequent major adverse cardiac events and all-cause mortality.

• Testing of prioritized targets from the multiomic analysis against the public OpenTargets platform revealed good evidence for the genetic involvement of F11, C1S, EGFR, IL6, & ANGPTL3 in cardiovascular diseases.

A novel proteomics approach to identify immunomodulatory drugs for psychiatric conditions

Major depressive disorder (MDD) is a relatively common neuropsychiatric disorder affecting well over 250 million people worldwide and is a significant global economic and healthcare resource burden. Evidence suggests that a subset of MDD patients exhibit a dysregulated immune system, suggesting pathophysiological overlaps with ostensibly unrelated diseases.

Scientists from the Icahn School of Medicine at Mount Sinai, New York investigated whether the proteomic profiles of MDD patients show similarities to patients with the inflammatory skin diseases atopic dermatitis (AD) and psoriasis (PS), where targeted immunomodulatory drugs have revolutionized treatment in recent years. Using multiple Olink® Target 96 panels, they looked for overlapping dysregulated proteins among MDD, AD, and PS patients and used a computational approach to explore repurposing opportunities to treat MDD with existing drugs approved for AD or PS therapy.

All three diseases had unique protein profiles, but a set of proteins including CCL13, CCl17 (Th2 cytokines), CXCL9, CXCL10, CXCL11 (Th1 cytokines), and CD40LG, TNFSF14 (T-cell markers) were dysregulated in all 3 patient groups.

Pathway analysis confirmed shared enrichment indicative of Th2 up-regulation in all three diseases.

In silico druggability analysis for these shared proteins identified the anti-IL-4Rα monoclonal antibody, dupilumab (commonly used to treat AD) as a potential opportunity for repurposing.

• Published data from clinical trials using dupilumab for AD revealed that several of the Th2 proteins shared between AD and MDD were affected by the drug.

Using a mouse model of psychosocial stress, they also showed that inhibition of IL-4Rα reduced stress-induced behaviors in these animals

Biomarker insights from a clinical trial for mRNA CAR-T cell therapy for myasthenia gravis

Chimeric antigen receptor (CAR)-T cell therapies could transform treatment of autoimmune disease by resetting the immune system, but adoption has been limited by issues such as the need for inpatient therapy, risk of cytokine release syndrome and non-specific immunosuppression.

RNA-based cell therapy may overcome some of these key limitations and a team from Cartesian Therapeutics (MA, USA) used the Olink® Target 96 Inflammation panel to monitor cytokine responses in patients with generalized myasthenia gravis (MG) in a phase 2b clinical trial, who were given Descartes-08, an autologous, RNA-encoded anti-B cell maturation antigen (BCMA) CAR-T cell therapy.

Administration of Descartes-08 in an outpatient setting resulted in durable clinical efficacy.

• Multiomic analysis indicated a precision retuning of self-reactivity demonstrated by increased pro-immune function, and reduced activity of BCMA+ plasma cells and plasmacytoid dendritic cells.

Olink analysis showed that administration of Descartes-08 was not associated with protein changes indicative of unwanted CAR-T cell therapy-induced inflammation.

A positive effect on decreasing multiple markers associated with autoimmunity was observed after 3 months, particularly reductions in IL-6, IL-24, CCL19, & ARTN.

Several other proteins relevant to autoimmune inflammation and immune reset decreased by month 12, including EN-RAGE, TRAIL, & TNFSF14.

• TGF-β1, which is involved in immune reset after CAR-T cell therapy, was also reduced at 12 months.

A custom biomarker panel defines CKD-associated protein responses in T2D patients treated with Dulaglutide

Chronic kidney disease (CKD) is a major complication of type 2 diabetes (T2D), affecting 20-50% of patients globally. The use of drugs such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) has significant benefits in this regard. Scientists from the Joslin Diabetes Center in Boston and Eli Lilly in Indianapolis carried out a post hoc proteomic analysis of the AWARD-7 clinical trial for the long-acting GLP-1RA drug, dulaglutide (Dula).

Previous biomarker discovery studies identified 64 circulating proteins strongly associated with elevated risk of end-stage kidney disease (ESKD) in individuals with diabetes. From these, they designed a 21-protein Olink® Flex panel, referred to as the Joslin Kidney Panel (JKP), which included key ESKD-associated markers including TNF receptors, immunoregulatory and other receptors, ligands, and inhibitors. This panel was used to measure longitudinal changes in plasma levels in trial participants treated with Dula or the insulin analog glargine.

While 14 JKP markers increased over 6 months in patients on glargine, they decreased in Dula-treated individuals with statistically significant between-group differences.

• The most significant differences were seen in 8 TNF receptors, as well as mediators of inflammation and apoptosis.

Stratification of patients by key clinical variables at baseline revealed differential effects of Dula based on these characteristics.

• The effects of Dula on circulating JKP proteins were 3 times larger in patients with severe vs moderate kidney dysfunction as measured by estimated glomerular filtration rate (eGFR).

Differences in JKP protein responses to Dula were also seen when stratifying by other key clinical factors – BMI, HbA1c, or UARC.