Profile: Celldex Therapeutics Inc (CLDX.A)
19 Aug 2019
Celldex Therapeutics, Inc., incorporated on December 9, 1983, is a biopharmaceutical company. The Company is focused on the development and commercialization of several immunotherapy technologies for the treatment of cancer and other diseases. The Company is using the technologies to develop targeted immunotherapeutics consisting of protein-based molecules, such as vaccines, antibodies and antibody-drug conjugates that are used to treat specific types of cancer or other diseases. The Company's lead drug Rintega (also referred to as rindopepimut and CDX-110) is a therapeutic vaccine, which is in clinical studies for the treatment of glioblastoma patients that express a specific cancer marker known as type III epidermal growth factor receptor mutation (EGFRvIII). Its Glembatumumab vedotin (also referred to as CDX-011) is a targeted antibody-drug conjugate for the treatment of metastatic melanoma. Its Varlilumab (also referred to as CDX-1127) is an immune modulating antibody that is designed to enhance a patient's immune response against their cancer. The Company's earlier stage drug candidates in clinical development include CDX-1401, which is a targeted immunotherapeutic aimed at antigen presenting cells (APC) for cancer indications and CDX-301, which is an immune cell mobilizing agent and dendritic cell growth factor. The Company's pipeline also includes CDX-0158 and CDX-3379.
CDX-0158 is a humanized monoclonal antibody that is a potent inhibitor of kinase inhibitors targeting (KIT) activation and receptor dimerization in tumor cells and mast cells. CDX-0158 is in Phase I dose escalation study in refractory gastrointestinal stromal tumors (GIST). CDX-3379 is a human monoclonal antibody designed to block the activity of ErbB3 human epidermal growth factor receptor 3 (HER3), which has completed a Phase Ib study with combination cohorts where responses and stable disease were observed in cetuximab (Erbitux) refractory patients in head and neck squamous cell carcinoma and in BRAF-mutant non-small cell lung cancer (NSCLC). It also includes a multi-faceted tumor-associated macrophage (TAM) program, which is an antibody discovery effort underway to generate antibodies that modulate the TAM family of receptor tyrosine kinases (RTKs), which are expressed on tumor-infiltrating macrophages, dendritic cells and some tumors.
Rintega is an EGFRvIII, which is a specific vaccine for glioblastoma (GBM). Rintega consists of the EGFRvIII peptide linked to a carrier protein called Keyhole Limpet Hemocyanin (KLH), and administered together with the adjuvant Granulocyte-macrophage colony-stimulating factor (GM-CSF). The Company has initiated Phase II study of Rintega prior to and concurrent with chemoradiation and maintenance temozolomide in patients with newly diagnosed EGFRvIII-positive glioblastoma, and also a Phase II single-arm study of Rintega with adjuvant imiquimod, a topically administered immune response modifier, in combination with Avastin in patients with recurrent EGFRvIII-positive glioblastoma.
Glembatumumab vedotin is an antibody-drug conjugate (ADC) that consists of a fully human monoclonal antibody, CR011, linked to a potent cell-killing drug, monomethyl-auristatin E (MMAE). The CR011 antibody specifically targets glycoprotein non-metastatic b (NMB), referred to as glycoprotein non-metastatic b (gpNMB) that is over-expressed in all cancers, including breast cancer and melanoma. The ADC technology, consists of MMAE and a stable linker system for attaching it to CR011, used in the marketed product Adcetris. The ADC is designed to be stable in the bloodstream. Following intravenous administration, glembatumumab vedotin targets and binds to gpNMB, and upon internalization into the targeted cell, glembatumumab vedotin is designed to release MMAE from CR011 to produce a cell-killing effect. The Food and Drug Administration (FDA) has granted fast track designation to glembatumumab vedotin for the treatment of advanced, refractory/resistant gpNMB-expressing breast cancer.
Varlilumab is a fully human monoclonal agonist antibody, which binds and activates CD27, a co-stimulatory molecule in the immune activation cascade, primarily by stimulating T cells to attack cancer cells. Restricted expression and regulation of CD27 enables varlilumab specifically to activate T cells, resulting in an enhanced immune response with a favorable safety profile. Varlilumab has also been shown to directly kill or inhibit the growth of CD27 expressing lymphomas and leukemias in vitro and in vivo.
CDX-1401 is developed from its APC Targeting Technology, which is an antibody-based NY-ESO-1-specific therapeutic vaccine for multiple solid tumors. In humans, NY-ESO-1 has been detected in over 20% to 30% of all melanoma, lung, esophageal, liver, gastric, prostate, ovarian and bladder cancers. The Company is developing CDX-1401 for the treatment of malignant melanoma and all solid tumors, which express the cancer antigen NY-ESO-1, which it licensed from the Ludwig Institute for Cancer Research. Preclinical studies have shown that CDX-1401 is effective for activation of human T cell responses against NY-ESO-1.
CDX-301 is a recombinant FMS-like tyrosine kinase 3 ligand (Flt3L), which is a potent hematopoietic cytokine that expands dendritic cells and hematopoietic stem cells in combination with other agents to potentiate the anti-tumor response. Depending on the setting, cells expanded by CDX-301 promote either enhanced or permissive immunity. CDX-301 is in clinical development for multiple cancers, in combination with vaccines, adjuvants and other treatments that release tumor antigens.
CDX-014 is a fully-human monoclonal ADC that targets T cell immunoglobulin and mucin domain 1 (TIM-1), a molecule that is upregulated in several cancers, including renal cell and ovarian carcinomas. TIM-1 is associated with kidney injury, and the shedding of its ectodomain is a predictive biomarker for tumor progression. CDX-014 has shown potent activity in preclinical models of ovarian and renal cancer.
The Company competes with AbbVie, Arbor Pharmaceutics, Inc., AstraZeneca PLC, Bayer, Bristol-Myers Squibb, Celgene Corporation, Eisai Inc., Eli Lilly and Company, Medigene AG, Northwest Biotherapeutics, Inc., Novartis, Novocure, Pfizer Inc. and Roche.
Celldex Therapeutics Inc
53 Frontage Rd Ste 220
HAMPTON NJ 08827-4034