Celldex Therapeutics, Inc. (Nasdaq: CLDX) today announced key in vivo efficacy data for its CDX-1135 program from a collaboration with Drs. Richard Smith and Carla Nester at the University of Iowa. The data were presented August 20, 2011 at the Fourth Dense Deposit Disease Focus Group in conjunction with the 13th European Meeting on Complement in Human Disease in Leiden, Netherlands. Dr. Smith presented in vitro and in vivo results, including data from animal models of Dense Deposit Disease (DDD) showing reversal of kidney damage after therapy with CDX-1135. CDX-1135 is a soluble, recombinant human Complement Receptor Type 1 (sCR1) that inhibits the classical, lectin and alternative complement pathways, both at the early (C3) and late (C5) activation steps in these pathways. Celldex's previous clinical experience with CDX-1135 in over 500 patients in other indications has shown a good safety profile and potent inhibition of complement pathways.
DDD is a rare but devastating disease where C3 activation leads to progressive kidney damage in children. There is currently no treatment for patients with DDD and about half progress to end-stage renal disease within 10 years. Because DDD recurs in virtually all patients who receive a kidney transplant, transplantation is not a viable option for these patients.
DDD is caused by uncontrolled activation of the alternative pathway (AP) of complement, which leads to the consumption of the circulating complement component C3, deposition of C3 in the kidneys, and subsequent damage to kidney function. Dr. Smith demonstrated that CDX-1135 can control the activation of AP complement in serum samples from DDD patients in vitro. In a mouse model of DDD, Dr. Smith showed that administration of CDX-1135 can control complement activation in vivo, preventing the damaging deposition of C3 in the kidneys.
"The results in mice are remarkable," stated Dr. Smith, "as no other interventions have shown control of the C3-based damage to the kidney." Initial experience in a patient with DDD treated by Drs. Smith and Nester showed control of the complement abnormalities. This patient was already in renal failure requiring dialysis and so reversal of disease was not expected. Drs. Smith and Nester hope that control of the complement abnormalities will be confirmed with further clinical testing in children with earlier stage disease, where C3 consumption and deposition plays an important role in disease progression, and CDX-1135 may be able to restore kidney function and provide long term disease control. Dr. Nester noted that "currently available complement inhibitors are only active against the C5 component of complement and are predicted to have little effect in DDD patients."
Dr. Thomas Davis, Chief Medical Officer of Celldex, added, "Celldex is excited to explore the potential role of CDX-1135 in C3 mediated disease, and we plan to begin clinical studies in 2012. We believe that blocking both C3 and C5 will provide more profound and complete disease control in children with DDD. We are also excited about the potential utility of CDX-1135 in other complement mediated disorders."
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