Zilosul (pentosan polysulfate sodium) / Paradigm Biopharma - LARVOL DELTA

A Study to Investigate the Treatment Effect of Subcutaneous Injections of Pentosan Polysulfate Sodium Compared With Placebo in Adult Participants With Knee Osteoarthritis Pain. (clinicaltrials.gov) - P3 | N=466 | Not yet recruiting | Sponsor: Paradigm Biopharmaceuticals Ltd.

New P3 trial • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

EFFECTS OF PENTOSAN POLYSULFATE SODIUM ON CLINICAL OUTCOMES AND DISEASE MODIFYING BIOMARKERS IN MODERATE TO SEVERE KNEE OSTEOARTHRITIS (OARSI 2024) - "Purpose (the aim of the study): Osteoarthritis (OA) is an inflammatory joint disease, causing chronic pain, disability, and reduced quality of life. Injectable pentosan polysulfate sodium (iPPS) targets inflammation by inhibiting transcription factor NF-κB, pain by normalizing NGF expression, and reduces cartilage-degrading enzymes."

Biomarker • Clinical • Clinical data • Immunology • Osteoarthritis • Pain • Rheumatology • NGF

Treatment Effects of Subcutaneous Injections of Pentosan Polysulfate Sodium vs Placebo in Participants With Knee OA Pain (clinicaltrials.gov) - P2/3 | N=602 | Active, not recruiting | Sponsor: Paradigm Biopharmaceuticals USA (INC) | Recruiting ➔ Active, not recruiting | N=938 ➔ 602

Enrollment change • Enrollment closed • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

An Observational Follow-up Study to Evaluate Duration of Treatment Effect of Pentosan Polysulfate Sodium in Participants With Knee Osteoarthritis Pain (clinicaltrials.gov) - P=N/A | N=133 | Active, not recruiting | Sponsor: Paradigm Biopharmaceuticals USA (INC) | Not yet recruiting ➔ Active, not recruiting | N=938 ➔ 133 | Trial completion date: Oct 2024 ➔ Dec 2025

Enrollment change • Enrollment closed • Trial completion date • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Theater Session: iPPS: Shifting the OA Treatment Paradigm (OARSI 2024) - "Understand how injectable pentosan polysulfate sodium (iPPS) could change the current OA therapeutic landscape. Get up to date with the drug development pathway, from the iPPS mechanism of action to relevant studies."

Therapeutic Effects of Pentosan Polysulfate Sodium on Clinical and Disease Modifying Outcomes in Subjects with Knee Osteoarthritis (ACR Convergence 2023) - "This study evaluated clinical and disease modifying biomarker and structural changes in subjects with knee OA pain treated with injectable pentosan polysulfate sodium (iPPS) or placebo... These findings show promising effects of iPPS for pain relief and improved function while changes in biomarkers and MRI assessments show potential DMOAD effects of iPPS in patients with knee OA. Paradigm is conducting larger global studies to confirm the observed clinical and DMOAD effects of iPPS. M."

Clinical • Immunology • Inflammation • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • COMP • IL6 • TIMP1 • TNFA

Australia’s Paradigm Biopharmaceuticals says phase 2 trial in osteoarthritis shows signs of disease modification at 6-month follow-upTop-line phase 2 trial data shows disease modifying potential and pain reduction (BioSpace) - P2 | N=61 | "Australia’s Paradigm Biopharmaceuticals Ltd...says analysis of six-month trial data shows injectable pentosan polysulfate sodium (iPPS) may slow the progression of osteoarthritis of the knee....In addition to reaching the primary endpoint, clinical scores using the Western Ontario McMaster Universities Arthritis Index (WOMAC) of pain and function at day 56 were statistically significant....The study was not powered for statistical significance and a 12-month data analysis will be released at the end of 2023."

P2 data • CNS Disorders • Osteoarthritis • Pain

An Exploratory, Phase 2 Clinical Trial In Knee Osteoarthritis Subjects Suggests Therapeutic Effects Of Pentosan Polysulfate Sodium On Synovial Fluid Biomarkers Of Pain, Inflammation And Chondroprotection (OARSI 2023) - "Injectable pentosan polysulfate sodium (iPPS, Zilosul™- Paradigm Biopharmaceuticals Ltd, Australia) is an investigational drug with disease modifying potential for OA treatment. PPS targets inflammation via inhibition of the transcription factor NF-κB, pain through the inhibition of NGF expression in osteocytes, and tissue preservation by inhibiting the cartilage-degrading enzymes. The purpose of this phase 2, randomized, double-blind, place-controlled study is to investigate changes in synovial fluid (SF) biomarkers in subjects with knee osteoarthritis pain treated with PPS compared with placebo-treated subjects."

Biomarker • Clinical • P2 data • Immunology • Inflammation • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • NF-κβ • NGF

Theater Session (OARSI 2023) - "Sponsored by Paradigm An overview of iPPS, a promising DMOADAn introduction to injectable pentosan polysulfate sodium (iPPS) with an exploration of imaging, synovial fluid, serum, and urine osteoarthritis biomarkers. A discussion of key results from two phase 2 trials and updates on the development pipeline."

Immunology • Osteoarthritis • Pain • Rheumatology

Paradigm Biopharmaceuticals Receives $5 Million Incentive Refund from Australian Government (Market Screener) - "Paradigm Biopharmaceuticals...received AU$7.4 million ($5 million) in research and development incentive refund under the Australian government's tax incentive scheme....The incentive will be used for Paradigm's clinical programs in osteoarthritis and mucopolysaccharidosis, as well as for other pre-clinical programs."

Financing • CNS Disorders • Osteoarthritis • Pain

Paradigm Biopharmaceuticals begins dosing first UK subject in pivotal iPPS/Zilosul trial (Proactiveinvestors) - "Paradigm Biopharmaceuticals Ltd (ASX:PAR) has randomised its first UK subject and kicked off dosing in the pivotal PARA_OA_002 phase 3 study, evaluating injectable pentosan polysulfate sodium (iPPS/Zilosul®) for the treatment of pain associated with knee osteoarthritis (OA). Notably, the company aims to activate a total of seven sites across the UK for this phase 3 study."

Trial status • CNS Disorders • Musculoskeletal Pain • Osteoarthritis • Pain

Paradigm Achieves Primary Endpoint in PARA_OA_008 Synovial Fluid Biomarker Phase 2 Clinical Trial (PRNewswire) - P2 | N=61| "Paradigm Biopharmaceuticals...is pleased to announce that the primary endpoint has been met and additionally significant improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores were demonstrated for injectable iPPS in the PARA_OA_008 phase 2 clinical trial....Participants have been randomised into three treatment groups according to a 1:1:1 ratio (19 randomised to iPPS twice-weekly, 20 randomised to iPPS once-weekly plus a placebo injection once-weekly, 22 randomised to placebo twice-weekly). Of the 61 patients, 48 (78%) had KL grades 3-4, and the average median baseline WOMAC scores were 6.6 for pain and 6.9 for function."

P2 data • CNS Disorders • Osteoarthritis • Pain

Paradigm raises AU$66M to fund pivotal trials for Zilosul for pain associated with knee osteoarthritis (Bioworld) - "Paradigm Biopharmaceuticals Ltd. announced a AU$66 million (US$46.39 million) capital raise to fund its phase III pivotal trial for injectable Zilosul (pentosan polysulfate) to treat osteoarthritis of the knee."

Financing • CNS Disorders • Osteoarthritis • Pain

Paradigm Biopharmaceuticals Completes Recruitment for Phase 2 Osteoarthritis Pain Trial; shares rise 3% [Google translation] (Market Screener) - "Paradigm Biopharmaceuticals...has completed enrollment for its phase 2 trial investigating the use of the drug Zilosul in patients with knee osteoarthritis-related pain...The interim study data is expected to be released in the third quarter of this year."

Enrollment closed • P2 data • CNS Disorders • Musculoskeletal Pain • Osteoarthritis • Pain

Paradigm Biopharmaceuticals (ASX:PAR) granted $8.2m R&D tax refund (The Market Herald) - "Paradigm Biopharmaceuticals...has received an $8.2 million research and development (R&D) tax incentive refund. The clinical stage biopharmaceutical company received a refund of $8,212,492 as part of Australia’s R&D tax incentive scheme....Paradigm qualified for the refund through its research activities for its pentosan polysulfate sodium (PPS) treatment which took place during the financial year ending June 30, 2021. Paradigm said it will use the funds to reinvest in further research and will continue to support its global phase three clinical program in osteoarthritis and mucopolysaccharidosis (MPS) which causes a progressive cognitive and motor decline through treatment with PPS."

Financing • CNS Disorders • Osteoarthritis • Pain

PARADIGM BIOPHARMACEUTICALS SPOTLIGHTS POTENTIAL BREAKTHROUGH OSTEOARTHRITIS TREATMENT AT BIOLOGICAL ASSOCIATION 3RD ANNUAL SUMMIT (Yahoo News) - "Paradigm Biopharmaceuticals Ltd...is honored that its Global Clinical Head of Osteoarthritis (OA) Mukesh Ahuja was selected to speak at the Biological Association 3rd Annual Summit, held in conjunction with the 2022 Arthroscopy Association of North America (AANA) Annual Meeting, in San Francisco. During his presentation, Dr. Ahuja introduced injectable pentosan polysulfate sodium (iPPS/Zilosul™), a repurposed drug with disease-modifying potential for OA treatment, and its mechanism of action. He explained that PPS looks promising as a Disease-Modifying Osteoarthritis Drug (DMOAD) while citing collected data and outlining Paradigm's ongoing work."

Clinical • Preclinical • CNS Disorders • Osteoarthritis • Pain

First Subjects Randomized and Dosed in the U.S. under Phase III Pivotal Trial for the Treatment of Pain Associated with Knee OA (PRNewswire) - "Paradigm Biopharmaceuticals...is pleased to report that the first subjects have been randomized and dosed in the United States (U.S.) in the PARA_OA_002 pivotal clinical trial, evaluating injectable pentosan polysulfate sodium (PPS/Zilosul®) for the treatment of pain associated with knee osteoarthritis (kOA)...eight sites across Australia and 21 of the 56 selected sites in the U.S."

Trial status • CNS Disorders • Osteoarthritis • Pain

Paradigm Biopharmaceuticals doses first US subjects in Phase 3 pivotal trial for treatment of knee osteoarthritis pain (Proactiveinvestors) - "Paradigm Biopharmaceuticals Ltd...has completed randomisation and begun dosing the first US subjects in the PARA_OA_002 phase 3 study evaluating injectable pentosan polysulfate sodium (PPS/Zilosul®) for the treatment of pain associated with knee osteoarthritis (kOA). This global pivotal study is screening and enrolling subjects in eight sites in Australia and 21 of 56 selected sites in the US. Paradigm has been keenly focused on ensuring a large pool of potential candidates are available for screening. Site activations in the US will continue and UK and EU sites will also be initiated throughout the calendar year."

Enrollment status • Trial status • CNS Disorders • Osteoarthritis • Pain

Paradigm Biopharmaceuticals secures US FDA fast-track for phase three osteoarthritis program (Proactiveinvestors) - "Paradigm Biopharmaceuticals Ltd...has been fast-tracked by the US Food and Drug Administration (FDA) for a phase three osteoarthritis program. The company’s Zilosul™[sic] candidate, a form of existing molecule Pentosan Polysulphate Sodium (PPS) which Paradigm is repurposing for osteoarthritis, has secured the regulatory green light."

Fast track designation • CNS Disorders • Osteoarthritis • Pain

Treatment Effects of Subcutaneous Injections of Pentosan Polysulfate Sodium vs Placebo in Participants With Knee OA Pain (clinicaltrials.gov) - P2/3 | N=938 | Recruiting | Sponsor: Paradigm Biopharmaceuticals USA (INC) | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Oct 2023 ➔ Oct 2024

Trial completion date • Trial primary completion date • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Treatment Effects of Subcutaneous Injections of Pentosan Polysulfate Sodium vs Placebo in Participants With Knee OA Pain (clinicaltrials.gov) - P2/3 | N=938 | Recruiting | Sponsor: Paradigm Biopharmaceuticals USA (INC) | Not yet recruiting ➔ Recruiting | Trial completion date: Jan 2023 ➔ Dec 2023 | Initiation date: Jun 2021 ➔ Oct 2021 | Trial primary completion date: Aug 2022 ➔ Oct 2023

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Paradigm Biopharmaceuticals osteoarthritis injectable trial proceeds to Phase 3 with an eye on US market (Proactiveinvestors) - "Paradigm Biopharmaceuticals Ltd...has randomised and dosed the first subjects in its PARA_OA_002 clinical trial. The randomised, double-blind and placebo-controlled trial, which is being conducted across the US, Australia, the UK, and Europe, will evaluate injectable pentosan polysulfate sodium (injectable PPS), registered as Zilosul®, for the treatment of pain associated with knee osteoarthritis."

Trial status • CNS Disorders • Osteoarthritis • Pain

Australia’s Paradigm Biopharma to start Phase III trial for knee osteoarthritis pain treatment (BioSpace) - "Paradigm Biopharmaceuticals...says it will begin registration studies in the United States and Australia in coming weeks to evaluate its lead compound, Zilosul® (pentosan polysulphate sodium) for patients with knee osteoarthritis pain (kOA). The US Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug application....Enrolment at 65 US and Australian trial sites will begin in December with UK and European sites to follow in 2022.The randomised, adaptive, double-blind, placebo-controlled, multicentre study called PAR_OA_002 will evaluate the dose and treatment effect of PPS compared to placebo in participants with kOA. The primary endpoint is a reduction in pain at day 56 assessed by the Western Ontario and McMaster Universities (WOMAC) pain scale..."

IND • New P3 trial • CNS Disorders • Osteoarthritis • Pain

Paradigm Biopharma (ASX:PAR) receives FDA feedback for knee osteoarthritis drug (The Market Herald) - "Paradigm Biopharmaceuticals (PAR) has received feedback from US Food and Drug Administration (FDA) for its knee osteoarthritis drug....The FDA has now requested modifications to Paradigm's adrenal screening and mitigation plan. The company will amend its clinical trial protocol, including all the FDA’s requests, and respond to the FDA within the next week."

FDA event • CNS Disorders • Osteoarthritis • Pain

Paradigm Biopharmaceuticals granted Australian ethics approval for pivotal Phase 3 clinical trial in participants with knee OA (Proactiveinvestors) - "Paradigm Biopharmaceuticals...approved drugs for new unmet medical needs, has received Australian ethics approval for a pivotal Phase 3 clinical trial, PARA_OA_002, to evaluate the treatment effects of pentosan polysulfate sodium (PSS) against placebo on participants with knee osteoarthritis (OA) pain....The primary endpoint will be change from baseline at day 56 in WOMAC ™ pain..."

Trial status • CNS Disorders • Osteoarthritis • Pain