Celldex is developing CDX-1135, soluble Complement Receptor Type 1 (sCR1, TP10), a specific and potent inhibitor of complement activation, for initial use in dense deposit disease (DDD) {sometimes called membranoproliferative glomerulonephritis type II (MPGN II)}. CDX-1135 has previously been evaluated in more than 500 patients in clinical trials and has been generally well tolerated with clear evidence of active complement inhibition. CDX-1135 inhibits the classical, alternative and lectin pathways of complement at both early (C3 convertase) and late (C5 convertase) stages by down-regulating the activation of these cascades. sCR1 affects only activated complement and is not consumed, but can recycle in the inhibitory process. Certain rare renal diseases, such as dense deposit disease, involve dysregulated complement and have been associated with mutations in complement proteins, including Factor H and Membrane Cofactor Protein (MCP). CDX-1135 has similarities to Factor H and MCP in structure and function, thus providing strong support for its potential efficacy in these diseases. In dense deposit disease, CDX-1135 has been shown to control the activation of alternative pathway complement in patient serum samples in vitro. In a mouse model of DDD, the administration of CDX-1135 was shown to control complement activation in vivo, preventing the damaging deposition of C3 in the kidneys. Short term compassionate use of CDX-1135 in a patient with dense deposit disease also showed control of complement abnormalities. This patient was already in renal failure requiring dialysis, so reversal of the disease was not expected.

Ongoing Clinical Trial in Dense Deposit Disease

A pilot study of CDX-1135 has been initiated to explore the potential for clinical benefit in patients with earlier stage dense deposit disease, where C3 consumption and deposition play an important role in disease progression, and where the greatest potential to restore kidney function and provide long term disease control exists. The open-label study will enroll up to five patients (ages four and older) from academic treatment centers across the United States to determine the dose level required to normalize alternative complement activity on an individual patient basis. Potential effects on renal function will also be assessed.

For more information on the CDX-1135 program, view recent scientific presentations and publications.