Celldex is currently developing antibody therapies for diseases with mast cell involvement, including chronic allergic/inflammatory disorders and autoimmune diseases.
Barzolvolimab (CDX-0159) is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity. KIT is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells. In certain inflammatory diseases, mast cell activation plays a central role in the onset and progression of the disease.
Chronic urticarias (Hives/Wheals)
Urticarias are red, itchy hives/wheals that result from an inflammatory skin reaction that are driven by activation of the mast cells in the skin. The condition is considered chronic if the hives appear for more than six weeks and recur frequently over months or years. These diseases can be severe and debilitating with a significant impact on quality of life and limited treatment options. Chronic urticarias can be inducible (caused by a specific trigger) or spontaneous (no known cause).
Chronic inducible urticaria (CIndU)
CindU is characterized by the occurrence of hives/wheals that are associated with a specific cause or trigger. The three most common triggers include: physical contact with the skin known as Symptomatic Dermographism (SD), cold or below body temperatures known as Cold Urticaria (CU) and sweating/ increases in body temperature known as Cholinergic Urticaria (CholU). Patients suffer both physically and psychologically with impaired quality of life.
Chronic spontaneous urticaria (CSU)
CSU is characterized by the occurrence of hives/wheals for 6 weeks or longer without identifiable specific triggers or causes. The activation of the mast cells in the skin (release of histamines, leukotrienes, chemokines) results in episodes of itchy hives, swelling and inflammation of the skin that can go on for years or even decades. Current therapies provide symptomatic relief only in some patients.
Prurigo nodularis (PN)
PN is a chronic skin disease that causes hard, intensely itchy lumps/nodules to form on the skin. Intense itching (pruritus) causes people to scratch themselves to the point of bleeding or pain – scratching can cause more skin lesions to appear, perpetuating the disease cycle. Mast cells are believed to play an important role in amplifying chronic itch and neuroinflammation. PN causes a significant quality of life impact: sleep disturbance, psychological distress, social isolation, anxiety, depression.
Eosinophilic esophagitis (EoE)
EoE is the most common type of eosinophilic gastrointestinal disease, a chronic inflammatory disease of the esophagus characterized by the infiltration of eosinophils. Chronic inflammation can result in trouble swallowing, chest pain, vomiting and impaction of food in the esophagus – a medical emergency. Currently, there are limited treatment options for EoE.
Other mast cell driven diseases
Celldex is currently examining multiple mast cell driven diseases to potentially expand the development of CDX-0159. These include dermatologic, respiratory, gastrointestinal, allergic and ophthalmic conditions.
Celldex is currently focused on cancers where the science and clinical data support the best potential for the treatments to provide benefit for patients. Antibody therapies in cancers are being developed by targeting multiple steps in the cancer immunity cycle, including dendritic cell, macrophage, and T cell activation, with an emphasis on improving immune deprived tumors.
CDX-1140 is a fully human antibody targeted to CD40, a key activator of immune response which is found on dendritic cells, macrophages and B cells and is also expressed on many cancer cells. CDX-1140 has unique properties relative to other CD40 agonist antibodies: potent agonist activity is independent of Fc receptor interaction, contributing to more consistent, controlled immune activation; CD40L binding is not blocked, leading to potential synergistic effects of agonist activity near activated T cells in lymph nodes and tumors; and the antibody does not promote cytokine production in whole blood assays.
CDX-1140 is being investigated in advanced solid tumors (monotherapy and in combinations), including:
Head and Neck Squamous Cell Carcinomas (HNSCCs)
HNSCCs develop from the mucosal epithelium in the oral cavity, pharynx and larynx and are the most common malignancies that arise in the head and neck. Given the complex nature of everyday functions within the head and neck area, the inherent consequences of HNSCC and its treatment have a large effect on the quality of life of patients.
Non-Small Cell Lung Cancer (NSCLC)
NSCLC accounts for approximately 85% of all lung cancers. There are several types of NSCLC, the most common types are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma, but there are several other types that occur less frequently, and all types can occur in unusual histologic variants.
CDX-527 is the first candidate from Celldex’s bispecific antibody platform. It uses Celldex’s proprietary highly active anti-PD-L1 and CD27 human antibodies to couple CD27 costimulation with blockade of the PD-L1/PD-1 pathway to help prime and activate anti-tumor T cell responses through CD27 costimulation, while preventing PD-1 inhibitory signals that subvert the immune response.
CDX-527 is being investigated in advanced solid tumors, including:
Ovarian cancer originates in the cells of the ovaries, including surface epithelial cells, germ cells and the sex cord-stromal cells. Epithelial ovarian cancer is the most common type and accounts for 85–89% of ovarian cancers. It forms on the surface of the ovary in the epithelial cells or from the fallopian tube. It ranks fourth in cancer deaths among women and causes more deaths than any other cancer of the female reproductive system.