New Jersey-based Celldex Therapeutics (NASDAQ:CLDX) has announced the results of a phase 1 clinical trial evaluating the pharmacokinetics, pharmacodynamics, safety, and effects of KIT inhibitor CDX-0159, which is intended to be used as a treatment for the mast cell-driven diseases chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CINDU).
The dose escalation study involved the intravenous administration of CDX-0159 or a placebo to 32 healthy individuals and evaluated for changes in the plasma levels of tryptase, a marker of mast cell activity, and of stem cell factor, a ligand that binds to the KIT receptor. The KIT receptor is a receptor tyrosine kinase expressed on the surface of mast cells, among other cell types, that is important for the expansion, differentiation, and survival of mast cells following activation. CDX-0159 is a monoclonal antibody that binds to and inhibits the activity of the KIT receptor.
Professor of Dermatology and Allergy and Director of Research at the Department of Dermatology and Allergy at the Allergie-Centrum-Charité of the Charité Universitätsmedizin in Berlin Dr. Marcus Maurer stated, “The profound decreases in plasma tryptase coupled with the favorable safety profile observed in this study suggest that CDX-0159 has significant potential as a disease-modifying therapeutic for mast cell disorders driven by wild-type KIT.”
“Chronic urticarias can have significant impact on quality of life, especially for patients with severe disease, where the intense itching can lead to insomnia, lack of energy, social withdrawal and depression. Currently approved therapies address the symptoms of the disease but not the root cause – the mast cells themselves. With continued positive data, CDX-0159 could be an important new drug for patients as it directly targets and inhibits mast cells. I look forward to results from future studies,” Dr. Maurer continued.
Senior Vice President and Chief Medical Officer of Celldex Therapeutics Diane C Young, MD, stated, “These results support the rapid advancement of CDX-0159 into clinical studies in our target patient populations. We look forward to initiating studies in chronic spontaneous urticaria and chronic inducible urticaria—both mast cell driven diseases—later this year.”
“Importantly, these indications will provide data read outs along the way with full data expected in chronic inducible urticaria early next year and in chronic spontaneous urticaria in the second half of 2021,” Dr. Young continued.
According to Celldex’s press release, “CDX-0159 demonstrated a favorable safety profile as well as profound and durable reductions of plasma tryptase, consistent with systemic mast cell suppression.”
“A single dose of CDX-0159 induced dose-dependent tryptase reduction below the level of assay detection within days at doses as low as 1.0 mg/kg and maintained suppression for over two months at 3.0 mg/kg and above.”
“Tryptase is an enzyme synthesized and secreted almost exclusively by mast cells and decreases in plasma tryptase levels are believed to reflect a systemic reduction in mast cell burden in both healthy volunteers and in disease, providing important proof of concept for the program.”
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“The data also support expansion of the program into mast cell driven diseases, including initially studies in forms of chronic urticaria (CU) given the central role mast cells are known to play in the etiology of CU.”
Moving forwards, the company plans to initiate a phase 1b clinical trial evaluating the utility of CDX-0159 for the treatment of chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CINDU) and is considering studying the medication in the context of other disorders as well.