LEADERSHIP IN FIBROSIS: Unique Benefits of PTX-2

Promedior’s lead product candidates include PRM-151, a recombinant form of human pentraxin-2 (rhPTX-2) being initially developed for rare systemic fibrotic diseases, and PRM-167 (rhPTX-2 variant for intravitreal injection), which is being developed for fibrovascular retinal diseases.  These drug candidates have the following dramatic benefits for the treatment and prevention of fibrotic, inflammatory, and autoimmune diseases:

• Targeting the source of fibrosis: Promedior’s initial pipeline of pentraxin therapeutics specifically targets monocytes and monocyte-derived cells at the site of tissue damage. PTX-2 specifically recognizes the chemical changes that occur when a cell becomes damaged (so called damage-associated molecular patterns or DAMPs) and binds to these damaged cells, thereby accumulating at the site of injury. Once bound to the damaged tissue, PTX-2 signals monocytes to remove the damaged cells and blocks their differentiation into fibrocytes or M2 macrophages, preventing the initiation and progression of the fibrotic disease process.
  
  
• Promoting healing and resolution: Promedior’s initial pipeline of pentraxin therapeutics also naturally stimulates monocytes and macrophages to differentiate into a beneficial, pro-resolution regulatory state that promotes healing and resolution of tissue damage at the site of injury. Local production of IL-10 by these regulatory macrophages at the site of injury inhibits the surrounding inflammatory and fibrotic macrophages and myofibroblasts, while inducing additional regulatory cell populations that amplify the beneficial, pro-resolution effects.
  
  
• Optimal efficacy profile: Because most current experimental anti-fibrotic therapeutics, such as anti-IL-13 and anti-TGFβ agents, inhibit only a single pathway within the broad array of redundant pathologic stimuli that drive fibrosis, they will likely have limited efficacy in treating chronic fibrosis. In addition, because these experimental drugs act as antagonists, their drug levels must be constantly maintained in order to retain efficacy. In contrast, Promedior’s pentraxin therapeutics act as partial agonists, are effective regardless of the number of pathologic stimuli present, and do not require continuous excess dosing, because their effect should last as long as the lifespan of the regulatory macrophages they stimulate. In fact, in fibrotic disease models Promedior’s lead pentraxin therapeutic, PRM-151, has demonstrated a durability of therapeutic effect far exceeding its presence in circulation.
  
  
• Reducing the risk of systemic side effects: Both experimental and conventional approaches risk severe and harmful side effects from weakening of the immune system as a whole, as they both require overwhelming the immune system stimuli with drugs. Conventional steroidal approaches are so broad in their immunosuppressive activity that they can fundamentally prevent healing via monocyte-driven resolution, as well as promote substantial side effects related to the large number of cell populations adversely affected. In contrast, by leveraging the natural power of monocyte regulatory biology, Promedior’s initial pipeline of pentraxin therapeutics switch on the appropriate regulatory function of the monocytes to promote healing, resolve inflammation and injury and avoid fibrosis and scarring.

Promedior has built a comprehensive patent estate for pentraxin therapeutics, including recombinant human pentraxin-2 (rhPTX2), for a broad range of therapeutic applications in fibrosis and other inflammatory diseases.

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