Promedior's drug candidates are based on Pentraxin-2, an endogenous human protein that is specifically active at the site of tissue damage and works as an agonist to initiate a resolution process for prevention and potential reversal of fibrosis. Promedior's Pentraxin-2 therapeutics harness the innate healing power of the immune system, acting as a master regulator upstream in the fibrosis cascade.
Normal wound healing consists of 3 distinct pathways: (1) inflammation, (2) proliferation, and (3) resolution. Fibrosis occurs when the normal wound healing response gets locked in the proliferation pathway, resulting in a cascade of excessive scar tissue that leads to tissue damage and organ dysfunction.
Pentraxin-2 directs the immune system to turn on the resolution pathway and simultaneously turn off the proliferation pathway, and works specifically in areas of tissue injury.
Pentraxin-2-based therapeutics have several advantages over other experimental approaches to treating fibrotic diseases:
- Potent Upstream Agonist: Scar formation is a highly conserved process with many downstream redundancies. By turning on the resolution pathway and thereby turning off the proliferation pathway upstream of significant redundancies, Pentraxin-2-based therapeutics offer the potential for a more robust approach to efficacy. In contrast, most competitive approaches target single downstream enzymes or cytokine targets, making it difficult to achieve efficacy without combination therapy.
- Specificity: Pentraxin-2's natural homing mechanism targets the damaged tissue microenvironment, ensuring that the drug effect only occurs in areas of disease. Less specific approaches could lead to unintended side-effects and toxicity.
- Potential to Reverse Fibrosis and Recover Function: By simultaneously promoting resolution and turning off the proliferation pathway, Pentraxin-2-based therapeutics offer the potential to break down scar tissue and promote recovery of organ function. Preclinical results have demonstrated the ability to reverse fibrosis – this reversal of fibrosis is possible due to the promotion of factors in the resolution pathway such as enzymes that break down the extracellular matrix in fibrotic tissue.
Extensive studies conducted by Promedior and its collaborators have demonstrated the ability of Pentraxin-2 to act as an upstream agonist which is specific for the damaged tissue microenvironment across many major tissue types and in several models of fibrotic disease, strongly supporting its potential as a novel anti-fibrotic agent. Promedior and its collaborators have published many of their findings in peer-reviewed journals
and presented them at medical and scientific meetings.