Nyrada Inc - Annual Report 2022

ANNUAL REPORT FY22 17 Testing Nyrada’s PCSK9 Inhibitor in a Model of Atherosclerosis On 19 July 2022, results from a study run by researchers at Duke University Pratt School of Engineering (Duke), using select candidates from Nyrada’s PCSK9 inhibitor family of compounds were presented at the North American Vascular Biology Organisation (NAVBO) 2022 Vasculata conference in North Carolina. The study aimed to determine if PCSK9 inhibitors attenuate inflammation in vascular cells in the early phases of atherosclerosis. In a human tissue-engineered blood vessel model of atherosclerosis, developed in the lab of Professor George Truskey, Nyrada’s PCSK9 inhibitor blocked the early stages of atherosclerotic plaque progression, including preventing monocyte adhesion and suppression of inflammatory cytokines, which are key mediators of the disease process. An optimised version of NYX-PCSK9i with superior pharmacokinetic parameters (improved absorption and distribution) was evaluated in this study. Accordingly, this compound will be assessed in Nyrada’s Phase I study in the first half of CY2023. It is the first time the model has been used to characterise the role of PCSK9 in the early phases of atherosclerosis and the potential for small molecule inhibitors of PCSK9 to block this process. The researchers at Duke intend to publish the findings of this study in a peer-reviewed paper. Preclinical Safety and Toxicity Studies During the second half of FY2022, an escalation in the number of COVID cases in Shanghai, China led to widespread lockdowns, which delayed the scale-up manufacture of Nyrada’s drug candidate, as employees of the contract manufacturing organisation (CMO) engaged by Nyrada were not able to access laboratory worksites. Drug manufacture was quick to recommence upon Shanghai’s reopening, with the CMO deploying additional personnel and resources to recover lost time. Impacted by the lockdowns, the required preclinical safety, pharmacology, and toxicology studies are expected to commence in H2 CY2022. These studies will evaluate the safety and tolerability of Nyrada’s drug and will be run at Inotiv, a US based contract research organisation (CRO). Data from these studies will determine the safe starting dose for the Phase I first-in-human study. Phase I Study The primary objective of the Phase I study is to evaluate Nyrada’s drug candidate for safety and tolerability. The study will be a double-blind, randomised, dose escalation design evaluating the safety, tolerability, and pharmacokinetics of Nyrada’s leading drug candidate in approximately 56 healthy volunteers aged 18 to 50 years. A secondary endpoint will assess blood cholesterol levels in cohorts treated for 14 days with Nyrada’s drug candidate as a preliminary indication of the drug’s efficacy in humans. Favourable results from the Phase I study will position Nyrada well for a possible Phase II clinical trial, which would provide a comprehensive assessment of the efficacy of Nyrada’s drug candidate in the target population, patients with a high cholesterol. As a result of scale-up drug manufacturing delays caused by COVID-related lockdowns in Shanghai, the Phase I first-in human study is expected to commence during the first half of CY2023. Objectives • Evaluate safety, tolerability, and pharmacokinetics of NYX-PCSK9i • Measure changes in LDL-cholesterol Design (subject to ethics approval) • Double-blind, randomized, placebo-controlled, dose escalation study • Single ascending oral dose (Cohorts 1-5) • Once daily oral dose over 14-day treatment period (Cohorts 6, 7) • Pharmacokinetic and pathology samples will be collected at selected time points over the trial period for all subjects Participants • 56 healthy volunteers (18 to 50 years) • 7 cohorts (6 active: 2 placebo per cohort) Location & Duration • Study will be conducted at a clinical trial center in Australia • The dosing period will vary between 1 – 14 days Cohorts 1-5 Cohorts 6-7 Day 1 Day 2 Day 14 Data analysis Single ascending oral dose Once daily oral dose