Paradigm Biopharmaceuticals Ltd. advised that the first safety review meeting of the Data Monitoring Committee (DMC) for the pivotal PARA_OA_002 clinical trial was conducted on 20 December 2022. The DMC review of trial progress and safety data concluded that the PARA_OA_002 clinical trial should proceed without modification. The DMC is responsible for assessing safety and efficacy during the conduct of Paradigm's PARA_OA_002 study, as well as ensuring the validity and scientific merit of the trial.

The Phase 3 Pivotal PARA_OA_002 clinical trial is a randomised, double-blind, placebo-controlled, multicentre (US/AU/UK/EU/CA) study that will evaluate the dose and treatment effect of injectable pentosan polysulphate sodium (iPPS) in participants with knee osteoarthritis (kOA) pain. About PARA_OA_002: The purpose of this study is to measure the change in pain and function with subcutaneous injections of iPPS compared with subcutaneous injections of placebo in participants with knee osteoarthritis (kOA) pain. This is a 2-stage, adaptive study that will evaluate the dose and treatment effect of iPPS in participants with kOA pain.

Stage 1 comprises phase 2b dose selection, with approximately 468 participants randomised to receive 1 of 3 iPPS dose regimens or placebo for 6 weeks. The primary objective of stage 1 is to identify the minimal effective dose that will be used in stage 2 and in Paradigm's confirmatory trial. The selected dose is based on an optimal balance of efficacy and safety.

Participants in stage 1 will be randomly allocated to receive one of the following: · 1.5 mg/kg calculated for ideal body weight (IBW) iPPS twice weekly; · 2 mg/kg IBW iPPS once weekly + placebo once weekly; · Fixed doses: o 100 mg iPPS for 65 kg IBW once weekly + placebo once weekly, or; o 150 mg iPPS for >65 to 90 kg IBW once weekly + placebo once weekly, or; o 180 mg iPPS for >90 kg IBW once weekly + placebo once weekly. Placebo twice weekly. In stage 2 (phase 3), approximately 470 participants will be randomised 1:1 to receive the selected iPPS dose regimen or placebo for 6 weeks.

Participants in stage 2 will be randomly allocated to receive: · One of the 3 stage 1 iPPS dose regimens selected by the DMC, or · Placebo twice weekly. The primary endpoint in the pivotal study is a change from baseline at day 56 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain. Secondary outcomes include change from baseline at multiple time points out to day 168 in WOMAC pain and function, Patient Global Impression of Change (PGIC), and Quality of Life (QoL).