E!11989 Secretoneurin (SN): a breakthrough blood biomarker for heart disease and sudden Cardiac Arrest risk

DELIVERABLES: D5.1: Report with SN levels, as measured by the new ELISA, across the SMASH 1 population (Delivery Month=29) D5.2: Report with results comparison of RIA and new ELISA across the SMASH 1 population (Delivery Month=29) KEY FINDINGS: 1. Changes in SN values are significantly correlated with severe and life-threatening arrhythmia and appropriate ICD triggering 2. SN is a very strong prognostic risk marker for mortality in a cohort of stable heart disease (implanted ICD) 3. Both SN at baseline and changes in SN concentration over time are associated with risk of heart failure hospitalization 4. The changes in SN concentration over time are measurable with the CardiNor SN ELISA test POSIBLE CLINICAL USE OF SN ELISA ? SN is a very strong risk marker for mortality in patients with stable heart disease. Use of an elevated SN baseline value, to optimize pharmacological treatment with e.g. dose titration and insertion of ARNI* (Entresto, Novartis) and SGLT1* inhibitor (different manufacturers) ? Risk marker for patients admitted to hospital with cardiovascular disease ? Monitoring of patients with respect to risk prediction to help identify when the patient should be discharged from the hospital. This would require several SN analysis during the stay. In the US, hospitals must cover the cost themselves if a patient is readmitted after a short time ? Retesting of SN at follow up to look at changes (delta) of SN o Patients with a clear increase in SN have a significantly increased risk of life-threatening arrythmia and might benefit from ICD treatment. This constitute by far the largest market segment for SN and will receive significant market support from all players in the ICD market (BSc, Abbott and Medtronic) o Patients with reduction in SN seem to have a lower risk of arrythmia, a change in SN could contribute to reclassify patients? risk.

Virkninger av resultatene. Vi har utviklet et produkt for som nå er klar for kommersialisering i forskningsmarkedet som RuO og det er allerede etablert kontakt med flere potensielle distributører i Europa og USA for salg og markedsføring av produktet. Vi forventer å signere kontrakter om få uker Basert på den utviklede ELISA teknologiplattformen har de parallellet blitt jobbet (ikke del av Eurostarsprosjektet) med CE merking av produktet som forventes sluttført Q3-2021 Den utviklede teknologiplattformen vil være fundament for utvikling av SN tester for automatiserte analyseplattformer som finnes på de store sykehusene verden rundt levert av Abbott, Roche og Siemens. Vi har søkt IPN prosjekt hos NFR på dette.

Project Management, Exploitation and Dissemination Develop monoclonal antibodies in sheep that bind to the referred peptide epitope with very high affinity and specificity, which will then allow setting up ELISA prototype assays: • Immunization of sheep with various SN, immunogens to generate antibodies • 2. Assay of sheep bleeds by ELISA to identify immune response and select best candidate sheep • 3. Harvesting of sheep lymphocytes • 4. Hybridoma fusions to create SMAs • 5. Screening by ELISA, cloning and selection of candidates to identify best suited SMA candidates for assay development. Development of ELISA assay for SN • Initial assay set-up • Assay configuration optimization • Final prototype assay optimization • Creation of standards and controls • Finalization of documents • Production validation Prototype testing against reference methods • Use the novel ELISA prototypes to measure SN levels across clinical cohorts and determine assay' characteristics to identify and select the best performing prototype for further optimization; • Correlate SN levels, as measured by the novel ELISA with the RIA reference method; • Assess prognostic accuracy of the SN ELISA with the accuracy of established risk indices and biomarkers; • Compare prognostic accuracy head-to-head between the novel SN ELISA and the SN radioimmunoassay across populations. Clinical validation of SN ELISA to identify high risk VA and SCD patients • To measure SN with the RIA and the prototype ELISA at the baseline and 12 month visit in all patients of the SMASH 1 Study • Correlate SN levels, as measured by the novel ELISA and the radioimmunoassay, across the SMASH 1 correlation • Assess prognostic accuracy of the SN ELISA with the accuracy of established risk indices and biomarkers in the SMASH 1 population • Compare prognostic accuracy head-to-head between the novel SN ELISA and the SN radioimmunoassay across the SMASH 1