Celldex Therapeutics Makes Significant Advancements in the Field of Protein-Based Vaccine Development

Celldex Therapeutics Makes Significant Advancements in the Field of Protein-Based Vaccine Development

Celldex Therapeutics, Inc.Sarah Cavanaugh, 781-433-3161Vice President of IR & Corp CommorBMC CommunicationsBrad Miles, 646-513-3125

(NASDAQ: CLDX) today announced positive results demonstrating promising clinical effects in a Phase 1 study of CDX-1401 in solid tumors in combination with the toll-like receptor (TLR) agonists resiquimod and/or Poly ICLC (Hiltonol). CDX-1401 is a fusion protein consisting of a fully human monoclonal antibody with specificity for the dendritic cell receptor DEC-205 linked to the NY-ESO-1 tumor antigen. The NY-ESO-1 antigen is expressed in a variety of cancer cells. Targeting protein antigens to the DEC-205 receptor on dendritic cells was pioneered by the late Ralph Steinman, MD, a member of Celldex’s Scientific Advisory Board. Dr. Steinman received the 2011 Nobel Prize in Physiology or Medicine for his discovery of the dendritic cell and its role in adaptive immunity. In preclinical studies, CDX-1401 has been shown to induce potent and broad immunity. The Phase 1 study of CDX-1401 is the first clinical study to demonstrate that an off-the-shelf vaccine that targets dendritic cells through DEC-205 can safely lead to robust humoral and cellular immunity when combined with TLR agonists in cancer patients - overcoming a significant challenge in the development of protein based vaccines.

“In the CDX-1401 study, we were able to translate the important preclinical work led by Dr. Steinman’s lab into clinical benefit, generating protein specific immunity including both antibody and T cell responses in patients with advanced cancers known to express NY-ESO-1. This is an important milestone for the field of targeted vaccine development and for the development of CDX-1401 specifically. Importantly, some patients had evidence of clinical benefit with significant stable disease and measurable tumor shrinkage, despite their advanced stage of metastatic disease. The ability to target proteins to dendritic cells represents a promising approach for the next generation of vaccines against pathogens and cancer,” said Madhav V. Dhodapkar, MBBS, Arthur H. and Isabel Bunker Professor of Medicine and Immunobiology, Chief of the Section of Hematology at the Department of Internal Medicine and Clinical Research Program Leader of the Hematology Program at Yale Cancer Center and the lead investigator of the study.

“CDX-1401 is at the forefront of a new generation of off-the-shelf dendritic cell targeted vaccines that Celldex believes hold significant promise as a platform for protein-based vaccines,” said Tibor Keler, PhD, Chief Scientific Officer of Celldex Therapeutics. “The immunological and clinical data demonstrated in this study clearly support continued investigation and we plan to study additional combination regimens of CDX-1401 in melanoma and other indications where we believe a dendritic cell vaccine regimen could play an important role. We expect that a study sponsored by the Cancer Immunotherapy Trials Network will be initiated in 2013.”

The results from the Phase 1 study of CDX-1401 were presented in a poster session entitled, “ at the Society for Immunotherapy Annual Meeting on Friday, October 26, 2012 by Dr. Dhodapkar. The study was conducted at multiple centers including Yale Cancer Center, Henry Ford Hospital and Medical Group, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, Providence Portland Medical Center, Mount Sinai Medical Center and the Carolina BioOncology Institute.

The Phase 1 study of CDX-1401 assessed the safety, immunogenicity and clinical activity of escalating doses of CDX-1401 plus resiquimod and/or Poly ICLC in 45 patients with advanced malignancies (21 melanoma, six ovarian, five sarcoma, four non-small cell lung cancer, four colorectal, five other) that had progressed after any available curative and/or salvage therapies. 87% of patients had distant metastases at entry. 60% of patients had confirmed NY-ESO expression in archived tumor sample. Ten patients received multiple cycles of the treatment regimen (six weeks of treatment followed by a six week rest), including five patients who received three or more cycles. Eight patients completed two years on study and eight patients remain in follow-up. Thirteen patients maintained stable disease for up to 13.4 months with a median of 6.7 months. In addition, two patients had significant tumor shrinkage (-20% and -21% decrease in area of target lesions). Treatment was well-tolerated and there were no dose limiting toxicities.

Significant anti-NY-ESO-1 titers (up to 1:800,000) occurred in 79% (33/42) of evaluable patients. Approximately 54% of patients with NY-ESO-1 positive tumors had anti-NY-ESO-1 titers at baseline and most increased after vaccination. Humoral responses were elicited in both NY-ESO-1 positive and negative patients. NY-ESO-1-specific T cell responses were absent or low at baseline, but increased post-vaccination in 53% (18/34) of evaluable patients, including both CD4 and/or CD8 T cell responses. Robust immune responses were observed with CDX-1401 with resiquimod and Poly ICLC alone and in combination. Importantly, a well-tolerated and immunogenic regimen has been identified to take forward into the future study.

CDX-1401 is a next-generation, off-the-shelf, cancer vaccine designed to activate the patient's immune system against cancers that express the tumor marker, NY-ESO-1. The product consists of a fully human monoclonal antibody with specificity for the dendritic cell receptor DEC-205 genetically linked to the NY-ESO-1 tumor antigen. Celldex has accessed NY-ESO-1 through a licensing agreement with the Ludwig Institute for Cancer Research. By selectively delivering the NY-ESO-1 antigen to dendritic cells in the body, this product candidate is intended to induce robust immune responses against the antigen-expressing cancer cells.

Celldex Therapeutics is the first antibody-based combination immunotherapy company. Celldex has a pipeline of drug candidates in development for the treatment of cancer and other difficult-to-treat diseases based on its antibody-focused Precision Targeted Immunotherapy (PTI) Platform. The PTI Platform is a complementary portfolio of monoclonal antibodies, antibody-targeted vaccines and immunomodulators used in optimal combinations to create novel disease-specific drug candidates. For more information, please visit .

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