Inflammatory conditions like arthritis involve signaling between inflammatory cells by cytokine molecules like TNF and IL-6.  Meyer Pharmaceuticals is developing a family of biological agents that prevent cytokine signaling by causing cytokine receptors to be shed from the cell membrane.  This is a new approach to treating inflammation, involving naturally occurring human proteins that are relatively inexpensive and that inhibit several different pathways.

Market leaders Remicade® and  Enbrel® (respectively a non-human antibody and a TNF receptor fusion protein) are artificial molecules that block TNF signaling by capturing TNF ligand.  In contrast, Meyer’s cytokine regulation agents generate soluble receptors from cells already present at the inflammatory site.  This allows the clinician to readjust the balance between pro-inflammatory and anti-inflammatory effects of the natural process of cytokine regulation.

Advantages of this approach to cytokine regulation:

• Dual mode of action:  Since the receptor is no longer present on the cell surface, it cannot transduce a cytokine signal into the target cell.  In addition, the released extracellular domain can bind and neutralize a mole of incoming TNF ligand. 
• Multiple pathways: One product can cause release of both TNF and IL-6 receptors, readjusting both pathways synchronously according to the natural balancing process. 
• Naturally occurring human protein:  Expected to be less immunogenic and have a more sustainable effect
• Ease of use:  These products are about one fifth the size of currently available biological agents, and are being developed for intramuscular administration
• Inexpensive to manufacture:  These agents are relatively small single-chain non-glycosylated proteins.  Unlike currently available biological agents, they can be produced in E. coli rather than mammalian cells

Meyer Pharmaceuticals lead product in this family is MP8.  This is a protein that regulates the primary enzyme that causes shedding of TNF and IL‑6 receptors.  MP8 is protected by seven issued U.S. Patents, over 20 other patents granted world-wide, and over 25 pending applications.

Meyer Pharmaceuticals has also identified and cloned enzymes directly responsible for the release of the TNF receptor.  These are described in pending patent application WO 2007/055979.