Paradigm Biopharmaceuticals Ltd (ASX:PAR) has released positive top-line results of the actions of pentosan polysulfate sodium (PPS) in the influenza model of acute respiratory distress syndrome (ARDS).
The preclinical study expands the PPS product pipeline from its use in the treatment of musculoskeletal indications in osteoarthritis (OA), Mucopolysaccharidosis (MPS) and alpha-viral induced arthralgia (RRV and CHIKV) into respiratory indications where acute inflammation in the lung is a potential therapeutic target of PPS.
Data summarising the effects of PPS in the exploratory model are being further evaluated in additional experimental models to assess translational relevance of these findings to human studies.
The complete data set of results including confirmatory studies will be prepared for peer review and publishing.
Paradigm has filed a patent for the treatment of ARDS with PPS.
“Very exciting results”
Paradigm’s chief executive officer Paul Rennie said: “This proof-of-concept preclinical study has provided very exciting results for our drug, pentosan polysulfate sodium (PPS) and it again demonstrates PPS is a platform technology.
“Paradigm is investigating in late-stage clinical trials the use of PPS in subjects with painful osteoarthritis, joint pain in subjects with the rare genetic disorder mucopolysaccharidosis (MPS).
“Preclinical proof-of-concept has been completed in joint pain as a result of viral arthritis and now promising data in an ARDS model.
“These ARDS preclinical data suggest that PPS may have a role to play in the acute and chronic phases of this disease”.
Further validating data
Paradigm chief science officer Dr Ravi Krishnan said: “I am very pleased that the data reported in this exploratory preclinical study of influenza virus induced ARDS has provided preliminary evidence that PPS administered subcutaneously in the acute phase of an inflammatory response has the possibility to target the cytokine ‘storm’.
“Furthermore, the observation that PPS appears to have durable biological activity for an animal study, extending into the post-acute phase of the response to regress the progression of pulmonary fibrosis in the lung is compelling.
“These findings may have potential implications in halting the progression towards chronic lung disease by early intervention with PPS at the onset of acute lung inflammation where there is a significant unmet medical need.
“Paradigm’s next steps are to consolidate and further validate these data to assess the preclinical translational relevance of these findings to identify the path to possible clinical trials in humans.”
Topline data results
The multiple mechanisms of action (MOA) of PPS have provided the scientific rationale for repurposing the agent in other indications with unmet or poorly met medical needs such as osteoarthritis and in alpha-viral induced arthralgia.
PPS treatment reduced lung inflammation, improved oxygen saturation and reduced weight loss compared to vehicle-treated controls at eight days post-infection (acute phase) in a mouse model of ARDS mediated by influenza infection.
Treatment with PPS demonstrated statistically significant reductions in the levels of complement 3a, a marker of tissue damage in the lung, and in serum levels of inflammatory biomarkers IL-6, INF-gamma, IL-12p70 and CCL2 in influenza-infected mice compared to vehicle-treated controls in the acute phase of infection.
PPS at the post-acute phase of infection (21-days post-infection) demonstrated a statistically significant reduction in pulmonary fibrosis compared to vehicle-treated controls based on histological staining of collagen.
Proof of concept data supports the potential investigation of PPS for the treatment of acute lung inflammation such as ARDS with ensuing pulmonary fibrosis as a result of viral infection.
Preclinical data supports the potential to expand the PPS product pipeline from its use in the treatment of musculoskeletal indications to acute and chronic respiratory indications with unmet needs.
Those with ARDS have severe shortness of breath and may subsequently develop fibrosis, a serious condition with unmet medical needs and limited therapeutic options.
ARDS
ARDS is a life-threatening condition in which fluid collects in the air sacs of the lungs, depriving organs of oxygen, resulting in severe shortness of breath, often requiring ventilation.
ARDS usually occurs in those who are critically ill or who have significant injuries. ARDS survivors may experience posttraumatic stress disorder, post-intensive care syndrome, long-term physical disability, neuromuscular weakness and persistent PF resulting in chronic lung dysfunction.
Pre-COVID, over 200,000 people were estimated to be living with PF in the US, with around 50,000 new cases diagnosed each year and as many as 40,000 deaths per year.
The full impact of chronic pulmonary fibrosis associated with the SARSCoV-2 virus on the overall prevalence of PF is yet to be determined.
Given the rapidity with which ARDS can cause fibrosis of the lung and the difficulty of reversing established fibrosis, an intervention is needed that prevents severe structural damage to the lung and thus tip the scales to facilitate repair to the injured lung.