Paradigm Biopharmaceuticals Completes Phase 3 Enrolment Ahead of September Interim Analysis

Paradigm Biopharmaceuticals (ASX: PAR) has completed enrolment in its global pivotal PARA_OA_012 Phase 3 study of Zilosul for knee osteoarthritis pain, with 538 participants commencing treatment across 65 clinical sites.

The final cohort exceeded the original 466-participant target after eligible candidates already progressing through screening were permitted to complete enrolment.

Database lock and data preparation for a pre-specified interim analysis are expected during August, followed by an independent Data Safety Monitoring Board (DSMB) review targeted for September 2026.

Primary endpoint top-line results remain anticipated during the first quarter of calendar 2027, placing Paradigm within months of its first Phase 3 efficacy assessment for injectable pentosan polysulfate sodium (iPPS).

Trial Shifts into Readout Phase

PARA_OA_012 is a multicentre, randomised, double-blind and placebo-controlled study operating in Australia, the US, Hong Kong, and Moldova, with participants receiving 2 milligrams per kilogram of iPPS subcutaneously twice weekly for six weeks.

Its primary endpoint measures the change from baseline in Weekly Average Daily Pain at Day 112, while secondary and exploratory assessments cover physical function, patient global assessment, responder outcomes, durability, and quantitative imaging.

The interim analysis uses the first 50% of participants reaching the relevant assessment milestone and can recommend continuation as planned, recognise early efficacy if the statistical threshold is met or terminate the study for futility.

“Completion of enrolment removes a major operational milestone and enables the Company to focus on treatment completion, patient follow-up, data preparation and delivery of the upcoming Interim Analysis,” executive chair Paul Rennie said.

“Paradigm is now entering a period of significant clinical and strategic catalysts—we remain focused on maintaining the quality and integrity of the Phase 3 program while continuing to advance regulatory, commercial, and partnering activities in preparation for the next stage of Zilosul’s development.”

No Safety Concerns

An independent DSMB safety review during the quarter assessed available data from about the first 20% of participants completing treatment and identified no material safety concerns.

The DSMB recommended continuation without changes to the protocol or study conduct, with further independent safety reviews planned under the trial design.

Paradigm is now concentrating clinical operations on treatment completion, follow-up assessments, safety monitoring, data management, and maintaining protocol integrity ahead of the Interim Analysis.

The dual clinical research organisation model remains in place, with Advanced Clinical managing Australia and the United States and Nordic Bioscience Clinical Development supporting Hong Kong and Moldova.

Evidence and Partnering Work

Phase 2 biomarker findings presented at the Osteoarthritis Research Society International 2026 World Congress showed changes across cartilage degradation, inflammation, pain and broader joint-tissue pathways.

Paradigm also submitted a manuscript covering magnetic resonance imaging (MRI) structural outcomes from the Phase 2 study, and began a 12-month research collaboration with City St George’s, University of London focused on bone marrow lesions.

Management continued regional and global licensing discussions for Zilosul at the BIO International Convention 2026 as the clinical program approached its Interim Analysis and primary endpoint readouts.

The group raised A$21.38 million through an institutional placement and Share Purchase Plan, ending June with A$15.37m cash before receiving A$5.69m in tax refunds and drawing about A$4.6m from its convertible note facility after quarter end.

Ample Funding for Key Milestones

June-quarter operating cash outflow was A$13.54m, including about A$13.3m invested in research and development activities as enrolment, treatment, and global trial execution reached peak activity.

After the post-quarter drawdown, about A$10.7m (US$7m) remained available through the company’s convertible note facility with Obsidian Global Partners.

Paradigm expects its available capital to support the Interim Analysis, Phase 3 top-line results and continuing regulatory, New Drug Application, manufacturing, and commercial-readiness work.

Full exercise of approximately 117 million attaching options from the raising at a price of A$0.2375 could provide about A$28m in additional funding, with each exercised option also generating a three-year piggyback option priced at A$0.38.