Paradigm Details How Its Lead Drug Slashes Cartilage Breakdown by Up to 74%
Paradigm delivers iPPS biomarker data at global osteoarthritis congress
Paradigm Biopharmaceuticals presented mechanistic biomarker findings from its Phase 2 osteoarthritis trial at the 2026 Osteoarthritis Research Society International (OARSI) Congress in Florida. Dr Donna Skerrett, Chief Medical Officer, delivered the oral theatre presentation on Friday morning US time, detailing how injectable pentosan polysulfate sodium (iPPS) affected cartilage, inflammation and pain pathways in patients with knee osteoarthritis.
OARSI is recognised as a leading international scientific meeting for osteoarthritis research, bringing together clinicians, researchers and industry to present advances in disease understanding and emerging therapies. The presentation, titled “iPPS Mechanistic and Clinical Effects Investigated by Biomarker Profiling,” covered results from trial PARAOA008, which enrolled patients with Kellgren-Lawrence radiographic grades 2, 3 and 4.
The biomarker data presented at the congress has been independently published in peer-reviewed journal Arthritis Research & Therapy in January 2026, providing external validation of the biological activity observed.
Conference presentations at OARSI provide visibility among key opinion leaders and potential partners ahead of Phase 3 data readouts, positioning the company’s development programme within the broader scientific community.
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What are biomarkers and why do they matter in drug development?
Biomarkers are measurable biological indicators that show whether a drug is having the intended effect at a molecular or cellular level. In osteoarthritis, biomarkers can track cartilage breakdown, inflammation levels, and pain signalling pathways, providing insight into how a treatment is working before final clinical trial results are available.
Biomarker profiling offers mechanistic evidence that a drug is active at the biological level, even when studies are not powered to demonstrate clinical efficacy. For iPPS, biomarker analysis across synovial fluid, serum and urine helps demonstrate activity across multiple pathways simultaneously.
Positive biomarker data strengthens the scientific rationale for ongoing Phase 3 trials and reduces development risk by showing biological plausibility. This type of evidence supports regulatory discussions and helps establish a drug’s mechanism of action beyond patient-reported outcomes alone.
Key biomarker findings from the Phase 2 trial
The headline finding presented at OARSI was an approximately 50–74% reduction in synovial ARGS versus placebo at Day 56. ARGS is a marker of cartilage matrix degradation, and reductions of this magnitude indicate substantial modulation of cartilage breakdown processes.
Paradigm reported reductions across multiple cartilage degradation biomarkers, including COMP, ARGS, C2C and CTX-II. The presentation also highlighted early reductions in inflammatory and pain mediators, specifically TNF-α and β-NGF at Day 56.
An increase in TIMP-1 was observed across the treatment period. TIMP-1 is described as an endogenous inhibitor of cartilage breakdown, suggesting iPPS may enhance natural protective mechanisms within the joint.
The presentation emphasised temporal differentiation in biomarker response. Early modulation of inflammation and pain pathways was followed by sustained effects on cartilage turnover and extracellular matrix biomarkers at Day 168, indicating different pathways are engaged at different timepoints during and after treatment.
| Biomarker Category | Key Markers | Observed Effect | Timepoint |
|---|---|---|---|
| Cartilage degradation | COMP, ARGS, C2C, CTX-II | Reductions | Day 56–168 |
| Inflammation | TNF-α | Early reduction | Day 56 |
| Pain signalling | β-NGF | Early reduction | Day 56 |
| Cartilage protection | TIMP-1 | Increase | Day 56–168 |
The Phase 2 study was a randomised, double-blind, placebo-controlled trial in 61 participants, evaluating a six-week course of subcutaneous iPPS.
Correlation with clinical outcomes
Correlation analyses demonstrated associations between biomarker changes and clinical improvements in WOMAC pain, stiffness and function. Patient Global Impression of Change (PGIC) also showed associations with biomarker modulation.
This supports a mechanistic link between biological activity measured in synovial fluid, serum and urine, and clinical benefit reported by patients. The Phase 2 study was not powered for clinical endpoints, but showed improvements in pain and function, particularly in the twice-weekly dosing group.
Demonstrating correlation between biomarker changes and patient-reported outcomes strengthens the case for iPPS efficacy ahead of Phase 3 results, providing evidence that the biological effects translate to meaningful clinical improvement.
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Implications for Paradigm’s Phase 3 programme
The biomarker findings presented at OARSI inform the design and execution of Paradigm’s ongoing Phase 3 trial, PARAOA012. The data supports the dosing regimen selected for the pivotal study and reinforces the focus on cartilage-related disease pathways as the primary mechanism of action.
Phase 2 mechanistic data reduces execution risk for the pivotal Phase 3 trial by providing evidence that iPPS engages the intended biological targets. This type of supporting data is valuable for regulatory discussions, as it demonstrates a clear pathway from molecular activity to clinical benefit.
The presentation at OARSI builds the scientific foundation for future regulatory submissions and positions iPPS within the broader field of disease-modifying osteoarthritis therapies. The biomarker profiling conducted across multiple biological compartments provides a comprehensive view of how iPPS affects joint biology in patients with established disease.
Recording available for investors
A recording of the oral presentation is available via Paradigm’s investor portal for those seeking detailed scientific content. The recording can be accessed at: https://investors.paradigmbiopharma.com/link/eNb1Ze.
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