Tumor Necrosis Factor alpha (TNFα) and Interleukin 6 (IL-6) are well established targets for treating inflammation.  Currently marketed anti-TNF biologicals relieve symptoms of rheumatoid arthritis, and help limit joint destruction.

Receptor Shedding as a Therapeutic Approach
There is a natural feedback mechanism that dampens inflammation, in which cells at and around the inflammatory site shed cytokine receptors from their surface.  The shed receptors complex with cytokines like TNFα and  IL-6, which prevents the cytokines from signaling affector cells, thereby limiting consequences of the inflammatory process. 

We have identified and produced recombinant versions of over ten naturally occurring human proteins (both enzymes and regulatory proteins) that inhibit the activity of pro-inflammatory cytokines by promoting TNF and IL‑6 receptor shedding.  Biological agents that work in this way represent a new approach to treating inflammation — an approach which is broadly protected by our patent portfolio.


Advantages of This Approach
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 biological agents generate soluble receptors from cells already present at the inflammatory site, thereby blocking several different cytokine signaling pathways by way of several mechanisms that replicate normal feedback.

Released receptors have a 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, in a manner analogous to anti-inflammatory biological agents currently on the market. 

Using receptor regulators and enzymes implicated in the shedding process as therapeutic agents has other advantages.  Several of these agents cause release of both TNF and IL‑6 receptors, potentially providing a broader therapeutic spectrum.  Furthermore, unlike currently available biological agents, all of the pharmaceutical candidates under development at Meyer are human proteins that are believed to participate in the natural feedback loop to control inflammation.

Our lead recombinant protein, MP8, is scheduled to begin clinical testing in rheumatoid arthritis in 2007.

Remicade® is a registered trademark of Centocor, Inc.
Enbrel® is a registered trademark of Immunex Corporation.