Celldex Reports Phase 1 Study Results of CDX-301, Says Data Support Starting Pilot Study

Celldex Therapeutics, Inc.

presented final results yesterday from a Phase 1 study of CDX-301 (recombinant human Flt3L; rhuFlt3L) in healthy volunteers that strongly support the initiation of a pilot study in hematopoietic stem cell transplantation later this year. The data were presented by Michael Yellin, MD, Vice President of Clinical Science at Celldex, in an oral presentation at the American Society for Blood and Marrow Transplantation 2013 BMT Tandem Meetings. The study was conducted at Rockefeller University by Niroshana Anandasabapathy, MD, PhD, who worked as an instructor in clinical investigation in the laboratory of the late Nobel Laureate Ralph Steinman, MD. "The final results from this study are consistent with previous clinical experience and demonstrate that CDX-301 is well-tolerated and can effectively mobilize hematopoietic stem cell populations as a single agent in healthy volunteers," said Dr. Yellin. "Based on the safety profile and the impressive increases observed for CD34+ stem cells and dendritic cells, we believe CDX-301 holds significant promise in both the allogeneic and autologous transplant setting, including the potential for combination with other molecules that could work in synergy with CDX-301 to further enhance the mobilization of hematopoietic stem cell populations. Published pre-clinical Flt3L studies also suggest that CDX-301 could potentially improve engraftment and reduce the risk of graph versus host disease. This may be especially important for older patients and patients who are in poor health." Study results: 30 healthy volunteers were enrolled across seven cohorts. The first five cohorts assessed escalating doses of CDX-301 (from 1 mcg/kg to 75 mcg/kg) as a five-day regimen, while the final two cohorts assessed CDX-301 (at 25 mcg/kg) as seven- and 10-day regimens. All volunteers completed dosing and safety follow-up. Short-term dosing of five days resulted in a median of 10-fold increases in CD34+ cells—stem cells that have the ability to give rise to all cell types in the blood. Of note, on day 10 of dosing, a greater than 100-fold increase in dendritic cells—cells believed to play a critical role in the long-term improvement of transplant outcome—was observed in the peripheral blood. CDX-301 was generally well-tolerated with transient grade 1 lymphadenopathy observed in six volunteers (all treated at the highest dose levels of 25 mcg/kg and 75 mcg/kg). No anti-CDX-301 antibodies were detected in any volunteers through the end of study follow-up. CDX-301 or rhuFlt3L is a potent cytokine that stimulates the expansion and differentiation of hematopoietic progenitor and stem cells. rhuFlt3L has demonstrated a unique capacity to increase the number of circulating dendritic cells in both laboratory and clinical studies. In addition, rhuFlt3L has shown impressive results in models of cancer, infectious diseases and inflammatory/autoimmune diseases. The clinical safety and activity of rhuFlt3L were originally demonstrated by Immunex (now Amgen) in clinical trials involving more than 150 healthy volunteers and 380 patients with cancer. Recognizing the promise of CDX-301, Celldex in-licensed the program from Amgen in 2009. Celldex's completion of this recent Phase 1 study confirms and builds upon the extensive prior clinical experience and reaffirms the significant potential for CDX-301.