Paradigm Biopharmaceuticals secures approvals for Phase 2 clinical trial treating MPS-VI subjects in Brazil with PPS

Paradigm Biopharmaceuticals Ltd (ASX:PAR) (OTCMKTS:PBIGF) has received a key regulatory approval from Brazilian National Health Surveillance Agency ANVISA for its Phase 2 clinical trial evaluating the safety and tolerability of injectable (SC) pentosan polysulfate sodium (iPPS) versus placebo in subjects with Mucopolysaccharidosis type VI (MPS VI). The company has also received ethics approval from the National Research Ethics Commission (Comissão Nacional de Ética em Pesquisa - CONEP) for the trial. A successful trial outcome will support partnering discussions for a registrational study to support the use of PPS, in conjunction with enzyme replacement therapy (ERT), in this orphan disease population. “Delighted to achieve milestone” Notably, the company’s MPS program has already received Orphan Drug Designation status in the US and EU for MPS I and MPS VI. Paradigm chief executive officer Paul Rennie said: “We are delighted to achieve this regulatory milestone during a busy period with the IND application process with the US FDA for our lead indication in Osteoarthritis. “Paradigm will be monitoring the current COVID situation in Brazil to plan the trial commencement and will update the market once a timeline is determined.” Shares have been as much as 7% higher in early trade to A$2.13 while PAR's market cap pre-open was approximately A$450.9 million. Trial design The phase 2, randomized, double-blind, placebo-controlled study will evaluate the safety and tolerability of PPS in treating subjects with MPS VI who exhibit pain and functional deficiency due to musculoskeletal symptoms associated with the underlying disease. Twelve (n=12) subjects will be recruited into the study and randomised 2:1, with eight (n=8) receiving PPS and four (n=4) receiving placebo. All MPS VI subjects will receive ERT throughout the study. Subjects will receive PPS at a 1.5 milligram/kilogram (≥9 years of age) or 1.0 milligram/kilogram (<9 years of age) dose or placebo by subcutaneous injection once weekly for 24 weeks.><9 years of age) dose or placebo by subcutaneous injection once weekly for 24 weeks. Study endpoints The primary objective of the Phase 2 study will be to evaluate the safety and tolerability of PPS in subjects with MPS VI at 6, 12, and 24 weeks. Paradigm will assess a number of key secondary and exploratory endpoints, including effect of PPS on: Pain and function (mobility); Urinary GAG levels; Walking-related pain; Quality of Life, activities of daily living, subject/parent global impression of response to therapy; and Pulmonary function. MPS VI patients in Brazil Brazil has the highest concentration of MPS-VI sufferers globally. It is recognised as an orphan disease, and classified as a rare autosomal recessive, inherited lysosomal storage disorder caused by a deficiency of N-acetyl galactosamine 4–sulfatase, leading to physical manifestations associated with accumulation of GAGs in the lysosomes. Generally the patients present as a dysmorphic syndrome (MPS IH, MPS II, MPS VI) often with early-onset middle ear disease, deafness, or upper airways obstruction; with learning difficulties, behavioural disturbance and dementia and mild somatic abnormalities (MPS III); and/or as a severe bone dysplasia (MPS IV). Current treatments for MPS VI patients include ERT which acts to replace the enzyme deficiency, however, MPS VI patients undergoing ERT therapy continue to report ongoing stiffness, pain and inflammation. The current standards of care are not adequate in treating the pain associated with joint inflammation and musculoskeletal issues.