Page 1 Nyrada Inc. Level 22/23, Salesforce Tower, 180 George Street, Sydney NSW 2000 ARBN 625 401 818 5 August 2026 Sydney, Australia CSANZ26 Conference Poster Nyrada Inc (ASX:NYR), a clinical-stage biotechnology company focused on developing Transient Receptor Potential Canonical (TRPC) ion channel inhibitors to treat a range of medical conditions, is pleased to provide a copy of a conference poster to be presented at the 74th Annual Scientific Meeting of the Cardiac Society of Australia and New Zealand (CSANZ26). Nyrada’s Director of Research and Development, Dr Jasneet Parmar , will be presenting at CSANZ 2026 to be held in Sydney from 6 to 9 August 2026. The poster presents preclinical data showing that Xolatryp® provided significant cardioprotection in two studies using a rat model of myocardial ischemia-reperfusion injury. The data from these studies show Xolatryp preserved myocardial structure and function while reducing ventricular arrhythmias following acute myocardial ischemia. Xolatryp is a small -molecule inhibitor of TRPC3/6/7 channels designed to limit excessive calcium entry related to multiple disease pathologies. A Phase I clinical trial to assess the safety, tolerability, and pharmacokinetics has been successfully completed and a Phase IIa clinical trial has commenced to assess the safety and preliminary efficacy of Xolatryp in reducing cardiac reperfusion injury in patients with ST-Elevation Myocardial Infarction (STEMI) undergoing PCI. Page 2 Nyrada Inc. Level 22/23, Salesforce Tower, 180 George Street, Sydney NSW 2000 ARBN 625 401 818 Key Links: Latest Corporate Presentation - https://bit.ly/4v0QgXE Foundation Studies • GLP study results – https://bit.ly/4d8VYkX • Phase I trial results – https://bit.ly/3Nt0GzH Cardiac Studies • Phase IIa PROTECT-MI website - https://www.protect-mi.com • Phase IIa study fact sheet – https://bit.ly/4bcDlKj • Preclinical cardioprotection study 1a - https://bit.ly/4sigwMZ • Preclinical cardioprotection study 1b - https://bit.ly/4rmOsXn • Preclinical cardioprotection study 2 - https://bit.ly/40jHpUg Oncology Studies • Preclinical anti-tumour study - https://bit.ly/49rWOa0 • Preclinical cardioprotection pilot study - https://bit.ly/3QS1VKm Stroke Study • Preclinical stroke study - https://bit.ly/4sygHmH TBI Study • Preclinical TBI study - https://bit.ly/40fhrRT Page 3 Nyrada Inc. Level 22/23, Salesforce Tower, 180 George Street, Sydney NSW 2000 ARBN 625 401 818 About Nyrada Inc. Nyrada Inc. is a clinical -stage biotechnology company focused on the discovery and development of innovative small -molecule therapies, specifically targeting Transient Receptor Potential Canonical (TRPC) ion channels. The company’s lead candidate, Xolatryp ®, has shown efficacy in preclinical cardioprotection, neuroprotection, and oncology models and has completed a first-in-human Phase I clinical trial. A Phase IIa clinical trial has commenced to assess the safety and preliminary efficacy of Xolatryp in reducing cardiac reperfusion injury in patients with ST -Elevation Myocardial Infarction (STEMI) undergoing PCI. Nyrada Inc. (ARBN 625 401 818) is incorporated in Delaware, US, with limited liability for its stockholders. www.nyrada.com Authorised by James Bonnar, Managing Director and CEO, on behalf of the Board. Investor & Media Enquiries: Company Secretary: Dimitri Burshtein David Franks T: 0491 789 391 T: 02 8072 1400 E: [email protected] E: [email protected] Forward-Looking Statements This announcement may contain forward -looking statements. You can identify these statements by the fact they use words such as “aim”, “anticipate”, “assume”, “believe”, “continue”, “could”, “estimate”, “expect”, “intend”, “may”, “plan”, “predict”, “project ”, “plan”, “should”, “target”, “will” or “would” or the negative of such terms or other similar expressions. Forward -looking statements are based on estimates, projections, and assumptions made by Nyrada about circumstances and events that have not yet taken place. Although Nyrada believes the forward -looking statements to be reasonable, they are not certain. Forward -looking statements involve known and unknown risks, uncertainties and other factors that are in some cases beyond the Company’s control (including but not limited to the COVID-19 pandemic) that could cause the actual results, performance, or achievements to differ materially from those expressed or implied by the forward-looking statement. GRAPHICAL ABSTRACT ➢ The safety and tolerability of Xolatryp was evaluated in a Phase I First-in-Human (FIH) study (NYR-BI03-01) as an IV infusion for up to 6 h. Xolatryp demonstrating a favourable safety profile ➢ The compelling cardioprotective and anti-arrhythmic efficacy observed in complementary rat myocardial ischaemia-reperfusion models directly informed the design of the ongoing PROTECT-MI Phase IIa clinical trial (https://clinicaltrials.gov/study/NCT07362446?term=PROTECT-MI&viewType=Card&rank=4). ➢ PROTECT-MI is a first-in-patient, randomised, double-blind, placebo-controlled, multicentre study evaluating whether a single 6-hour intravenous infusion of Xolatryp, administered as an adjunct standard of care in STEMI patient undergoing primary PCI is safe and well tolerated. Efficacy is explored as secondary and exploratory end points. ➢ Clinical outcomes will measure the incidence of AEs and SAEs with efficacy redouts including infarct size, ejection fraction, fractional shortening, serial blood cardiac biomarkers, arrhythmia monitoring and safety assessments to determine whether the cardioprotective effects observed preclinically translate to patients undergoing reperfusion therapy. Experimental Design Generic experimental paradigm for rat myocardial ischaemia-reperfusion studies Baseline, anesthesia Induction of ischaemia (occlusion) Restoration of blood flow (reperfusion) Xolatryp or vehicle IV infusion ECG Echocardiography, left ventricular function Blood biomarkers, e.g. cardiac troponin I Heart harvest, TTC staining for infarct volume Study A - Proof of Biology Continuous IV Administration of Xolatryp Preserves Myocardial Structure and Function Following Acute Myocardial Ischaemia Study Overview - Rat Myocardial Ischaemia-Reperfusion Model 24 h IV infusion Endpoints (24 h) Reperfusion, (restoration of blood flow) 30 min LAD occlusion Echocardiography Blood biomarkers TTC staining Study Details • Male Sprague-Dawley Rats • n = 8 per group • Xolatryp 1.25 mg/kg/h IV infusion • Infusion commenced 5 min before reperfusion and continued for 24 h Treatment Groups Sham, vehicle I/R, vehicle I/R, 1.25 mg/kg h Xolatryp (IV) I/R, 30 mg/kg Captopril (oral) Preservation of Myocardial Structure by Xolatryp TTC-stained Heart Sections (Representative) Sham, vehicle I/R, vehicle I/R, 1.25 mg/kg h Xolatryp I/R, 30 mg/kg Captopril Sham, vehicle I/R, vehicle I/R, Xolatryp I/R, Captopril Preservation of Cardiac Function by Xolatryp (Echocardiography) Fractional Shortening Ejection Fraction Left ventricular diameter end systole Plasma Biomarkers of Cardiac and Liver Injury Xolatryp-Induced Reduction vs I/R Vehicle (%) Cardiac Troponin I (cTnI) 32% p = 0.18 AST (Liver Biomarker) 45%** ** p < 0.05 Lactate Dehydrogenase 42%** ** p < 0.05 Key Finding Continuous IV administration of Xolatryp immediately before reperfusion produced profound cardioprotection, reducing myocardial infarct size by 86%, preserving left systolic function and attenuated biochemical markers of injury Abbreviations: LAD, left anterior descending coronary artery; TTC, 2,3,5-triphenyltetrazolium chloride; AST, aspartate aminotransferase; I/R, ischemia/reperfusion; IV, intravenous; cTnI, cardiac troponin I. Xolatryp® - a Gαq-Coupled TRPC Channel Antagonist Attenuates Myocardial Reperfusion Injury and Malignant Arrhythmias in Rat MI Models Study B - Proof of Translation Short Duration IV Infusion of Xolatryp Preserves Myocardium and Cardiac Electrical Stability Following Acute Myocardial Ischaemia in Rats Study Overview Male Sprague-Dawley Rats (n = 10) LAD occlusion 35 mins Start Xolatryp infusion Reperfusion 180 mins Assessments Preservation of Myocardial Tissue (TTC Staining) Sham, vehicle I/R, vehicle I/R, 0.9 mg/kg Xolatryp I/R, 3 mg/kg Xolatryp I/R, 9 mg/kg Xolatryp I/R, vehicle 0.3 3 9 I/R, Xolatryp (mg/kg) reduction in infarct size at 9 mg/kg Xolatryp versus I/R vehicle42% Reduced Plasma Biomarkers Reduction in Infarct Size Cardiac Troponin I (cTnI) I/R, vehicle 0.3 3 9 I/R, Xolatryp (mg/kg) Alanine Transferase (ALT) I/R, vehicle 0.3 3 9 I/R, Xolatryp (mg/kg) 9 mg/kg Xolatryp-Induced Reduction vs I/R Vehicle (%) Cardiac Troponin I 32% p = 0.014 Alanine Transferase 21% p = 0.0202 Reduced Ventricular Premature Beats (VPBs) Continuous ECG Monitoring During 3 h Reperfusion After Ischaemia 1 2 3Time (h) Vehicle 1 2 3 0.3 mg/kg Xolatryp 1 2 3 3 mg/kg Xolatryp 1 2 3 9 mg/kg Xolatryp reduction in VPBs by 9 mg/kg Xolatryp versus I/R vehicle at 3 h reperfusion 90% Decreased Ventricular Tachycardia and Fibrillation (VT/VF) VT VF I/R, vehicle I/R, vehicle I/R, 9 mg/kg Xolatryp I/R, 9 mg/kg Xolatryp Xolatryp completely suppressed VFs and markedly reduced VTs throughout 3 h of reperfusion Key Finding A short IV administration of Xolatryp dose-dependently produced cardioprotection, reduced cardiomyocyte injury, suppressed ventricular ectopy and curtailed malignant ventricular arrythmias after myocardial ischaemia-reperfusion injury TRPC ion channel signalling pathway Target engagement – Xolatryp inhibits human TRPC channels Dose-response inhibition of calcium influx in HEK-293 cells Xolatryp inhibits human TRPC3, TRPC6, TRPC7 channels in a concentration-dependent manner Background Acknowledgements The authors gratefully acknowledge the contributions of: • Pharmaron, Inc. (Louisville, Kentucky) for conducting Study A. • Sichuan Greentech Biotechnology Co., Ltd. (Chengdu, China) for conducting Study B. • Sygnature Discovery Ltd. (Nottingham, United Kingdom) for undertaking the in vitro TRPC3/6/7 channel pharmacology and concentration–response assays. • The investigators, research staff and patients participating in the ongoing PROTECT-MI Phase IIa clinical trial. Disclosures This work was funded by Nyrada Inc. B.E., J.P., A.S., P.C. and J.B. are employees and/or shareholders of Nyrada Inc. G.D. Housley serves as a scientific advisor to Nyrada Inc. and shareholder. Xolatryp® is an investigational medicinal product being developed by Nyrada Inc. Clinical Translation • Primary percutaneous coronary intervention (PCI) restores coronary blood flow following ST-elevation myocardial infarction (STEMI), but reperfusion itself initiates secondary myocardial injury that contributes to infarct expansion, ventricular dysfunction and malignant arrhythmias. • Pathological activation of Gαq-coupled receptor signalling during reperfusion stimulates TRPC3/6/7 channels, promoting excessive intracellular Ca²⁺ influx, mitochondrial dysfunction, oxidative stress and cardiomyocyte death. • Xolatryp® is a potent, selective antagonist of TRPC3, TRPC6 and TRPC7 that targets this upstream calcium signalling pathway to preserve myocardial viability while maintaining physiological cardiac function. • This study evaluated whether pharmacological inhibition of TRPC3/6/7 with Xolatryp reduces myocardial reperfusion injury and improves structural, functional and electrophysiological outcomes in rat models of acute myocardial infarction B. Evison1, J. Parmar1,2, A. Suchowerska1,2, P. Coghlan1, G.D. Housley2, J. Bonnar1 1Nyrada Inc., Sydney, NSW, Australia 2Translational Neuroscience Facility & Dept. Physiology, School of Biomedical Sciences, UNSW Sydney, Sydney, NSW, Australia Presenter: Dr Jasneet Parmar Director, R&D Nyrada Inc Cardiac Cell TRPC Activation Potential Xolatrp Effect Cardiomyocytes Cell injury Preserved function Endothelial cells Endothelial dysfunction Improves perfusion Fibroblasts Fibrosis Limits remodelling Abbreviations: LAD, left anterior descending coronary artery; TTC, 2,3,5-triphenyltetrazolium chloride; AST, aspartate aminotransferase; I/R, ischemia/reperfusion; IV, intravenous; cTnI, cardiac troponin I. p < 0.001 p < 0.0001 p < 0.001 One way ANOVA, Holm-sidak post hoc Kruskal-Wallis test One-way ANOVA with Bonferroni t-test post-hoc One-way ANOVA with Bonferroni t-test post-hoc One-way ANOVA with Bonferroni t-test post-hoc Two Way Repeated Measures ANOVA, Bonferroni’s t-test
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