Slide 1: Post-Acute Sequelae of Long COVID-19 (PASC) SomaScan Proteomics Analysis
Post-Acute Sequelae of Long COVID-19 (PASC) SomaScan® Proteomics Analysis Tracking the impact on ~7000 plasma proteins in PASC 19 August 2022 Blood samples from PASC Patients evaluated to identify opportunities for the diagnosis, prognosis and better treatment of Neurological PASC
Slide 2: Antisense Therapeutics Limited – Presentation Disclaimer
Antisense Therapeutics Limited – Presentation Disclaimer This presentation contains certain market estimates and forward-looking statements regarding the Company’s business & the therapeutic & commercial potential of its technologies & products in development. Any statement provided by the Company o
Slide 3: Antisense Therapeutics SomaScan Neurological Long COVID-19 Findings
Antisense Therapeutics SomaScan® Neurological Long COVID-19 Findings • World first study to assess up to 7,000 plasma proteins in Long COVID-19 patients • Collaboration with Feinberg School of Medicine NorthWestern University Chicago and NorthWestern Medicine Neuro-Covid Clinic1 • Retained blood sam
Slide 4: Of the 94.7 million people in the US diagnosed as infected and surviving COVID-19
Of the 94.7 million people in the US diagnosed as infected and surviving COVID-191, approximately 82 million (87%) people are non- hospitalized and 45% of non-hospitalized patients2 have developed some manifestation of Long COVID-19 syndrome which suggests more than 24 million people are afflicted b
Slide 5: Acknowledged need for diagnostic and therapeutic approaches
Acknowledged need for diagnostic and therapeutic approaches 5 https://www.msn.com/en-us/health/medical/brain-fog-and-other-long-covid-symptoms-can-last-more-than-a-year-according-to-study/vi-AA10gBis
Slide 6: Timeline of post-acute COVID19 infection
Timeline of post-acute COVID19 infection https://www.nature.com/articles/s41591-021-01283-z From Nalbandian et al Nature Medicine 27, 601-615 (2021) Neurological Post- Acute Sequelae of COVID-19 (PASC) NPASC (can include fatigue) The WHO definition of PASC is at >12 weeks post acute COVID-19 symptom
Slide 7: Methods- Samples
Methods- Samples • Blood samples from 92 subjects (48 patients with Neurological-PASC) were sent to SomaLogic® • Plasma samples were tested using the SomaScan® assay, a large scale, aptamer-based assay • The normalized relative fluorescence units (nRFU) of over 7000 proteins was determined for the f
Slide 8: Methods –Statistics Dataviz
Methods –Statistics Dataviz Somalogic® provided an ADAT file of data that was uploaded to their Dataviz program after logging in and starting the statistical tests. The file is then filtered by “sample type” and the Buffer, QC and Calibrator samples are removed leaving only “Sample” - A .csv file wa
Slide 9: Methods-Statistics (T test and U test)
Methods-Statistics (T test and U test) Parametric and Non-parametric tests to 1 vs 3 1 vs 4 1 vs 3+4 3 vs 4 identify protein markers of interest Bonferroni < 0.05 1 30 45 0 FDR< 0.0005 0 11 22 0 • T test and U test comparing T-TEST FDR <0.01 0 184 440 0 • Group 1 to 3, FDR < 0.03 0 0 FDR <0.05 25 89
Slide 10: Results Bonferroni T test < 0.05 (G1 vs G3)
Results Bonferroni T test < 0.05 (G1 vs G3) Data Viz Box plots shows Outliers, The upper whisker also known as the upper fence, Interquartile range, lower whisker also known as the minimum (or lower fence) • 1 Target ‘S’ was identified in the parametric T –test with Bonferroni of <0.035 • The median
Slide 11: Results Bonferroni U test < 0.05 (G1 vs G3)
Results Bonferroni U test < 0.05 (G1 vs G3) • 2 targets were identified in the non-parametric U –test, Bonferroni statistical analysis Target ‘M’ Q3 also detected in the FDR<0.02 stats Target ‘G’ also detected in the FDR<0.02 stats 13% increase in the median in G1 vs G3 22% decrease in median in G1
Slide 12: Methods- Statistics (ANOVA and Kruskalis Wallis)
Methods- Statistics (ANOVA and Kruskalis Wallis) • ANOVA and Kruskalis Wallis (KW) tests were conducted comparing Group 1, 3 and 4 with • p-values adjusted using Benjamini-Hochberg false discovery rate (FDR) and • Bonferroni statistical tests, was used to identify proteins of interest, • using Somal
Slide 13: Results - Number of hits with ANOVA and KW
Results - Number of hits with ANOVA and KW 1v 3 v4 Bonferroni < 0.05 31 FDR< 0.0005 2 ANOVA FDR <0.01 149 FDR <0.02 314 FDR <0.05 778 FDR < 0.075 1128 Bonferroni < 0.05 9 FDR< 0.0005 0 Kruskalis Wallis FDR <0.01 118 FDR <0.02 284 FDR <0.05 905 FDR < 0.075 1411 Target and Pathway Analysis was done on
Slide 14: A marker of peripheral nerve damage in Autoimmune disease
A marker of peripheral nerve damage in Autoimmune disease • One of the 33 targets “G” identified was a marker of peripheral nerve damage in an autoimmune disease • The Median levels of G was significantly elevated 29% in the Neuro PASC patients group 1+2, vs G3, G4 • Modulation of this target sugges
Slide 15: Results-ANOVA Bonferonni Pathway Analysis
Results-ANOVA Bonferonni Pathway Analysis • Pathways were identified in inflammation and apoptosis Pathway Analysis (Column K) Inflammatory Apoptosis/ Apoptosis WikiPathways Signaling Response Pathway Modulation and (4/4) Pathway (IFR) Signaling (APO) KEGG (5/9) Signaling Signaling C Apoptosis C HIT
Slide 16: Results- Kruskalis Wallis Bonferroni < 0.05
Results- Kruskalis Wallis Bonferroni < 0.05 • The 2nd target marker elevated, based on published data on the protein, we 16 theorize indicates the body’s attempt to repair neurological damage in NPASC
Slide 17: Results-ANOVA & KW FDR & Pathway Analysis
Results-ANOVA & KW FDR &Pathway Analysis 1v 3 v4 *Bonferroni < 0.052 31 • Pathway analysis of those markers with an FDR< 0.0005 2 FDR < 0.02 identified pathways involving ANOVA FDR <0.01 149 • Platelets FDR <0.02 314 FDR <0.05 778 • Inflammation and Fibrosis FDR < 0.075 1128 • Integrins *Bonferroni
Slide 18: Results - Targets with approved drugs- therapy (ANOVA FDR <0.02)
Results - Targets with approved drugs- therapy (ANOVA FDR <0.02) Target FDR % change NP • The 314 targets in the ANOVA FDR < 0.02 were 1. 0.007 +28% looked for in a database of targets to which 2. 0.0071 -22% there are drugs approved 3. 0.01 +15% • 12 targets were identified as potentially 4. 0.011
Slide 19: Box Plots of Targets 1-3 of 12 with approved drugs- therapy
Box Plots of Targets 1-3 of 12 with approved drugs- therapy 19
Slide 20: Box Plots of Targets 4-6 of 12 with approved drugs- therapy
Box Plots of Targets 4-6 of 12 with approved drugs- therapy 20
Slide 21: Box Plots of Targets 7-9 of 12 with approved drugs- therapy
Box Plots of Targets 7-9 of 12 with approved drugs- therapy 21
Slide 22: Box Plots of Targets 10-12 of 12 with approved drugs- therapy
Box Plots of Targets 10-12 of 12 with approved drugs- therapy 22
Slide 23: Potential Diagnostic Therapeutics Markers – Combination of 3-5 markers
Antisense Potential Diagnostic Therapeutics Markers SomaScan® –Combination of 3-5 markers Neurological Long COVID-19 Findings • A combination of 3 markers identifies all 48/48 NPASC subjects • i.e providing high sensitivity for detection of subjects with NPASC • The combination of 3 markers plus ano
Slide 24: Potential Diagnostic Markers – Combination of 1 and 2
Potential Diagnostic Markers – Combination of 1 and 2 The upper whisker interquartile range, lower whisker, outliers and extreme values for each of the 48 subjects in G1+2, 20 subjects in G2, and 24 24 subjects in G4 are shown
Slide 25: Potential Diagnostic Markers - Combination of 3 and 2
Potential Diagnostic Markers - Combination of 3 and 2 25
Slide 26: Potential – Backup Diagnostic Markers differentiate HC/CC
Potential – Backup Diagnostic Markers differentiate HC/CC 26
Slide 27: 3 US Provisional patent applications filed
Antisense 3 US Provisional patentTherapeutics SomaScan® applications filed Neurological Long COVID-19 Findings • Diagnostics provisional patent application titled “Biomarkers and Uses thereof” • Therapeutic provisional patent application titled “ Methods for treating neurological post-acute sequelae
Slide 28: Acknowledgements
Acknowledgements INITIAL PATIENT TRIAL SAMPLES SOMALOGIC® FOR SOMASCAN® ASSAY Clinical Researchers Statistician Professor Igor Koralnic and his Colleagues from the Robert Kirk DeLisle 1 Ken and Ruth Davee Department of Neurology, Feinberg SomaLogic Operating Company, Inc School of Medicine, Northwes