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Biotech / Medical : CLDX Celldex Therapeudics

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Oct 31 9:30 AM EST

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From: scaram(o)uche	1/12/2020 12:49:21 PM
	of 105

tandfonline.com >> The first agonistic antibody to enter the clinic was developed by Pfizer, the CP-870,893 (now pursued in the clinic by Hoffman-la Roche with the generic name selicrelumab). This is an IgG2 antibody developed from the Abgenix Xenomouse® platform that binds CD40 with nanomolar affinity [3] without competing with the CD40L binding site [4]. << >> The maximum tolerated dose (MTD) as a single-dose was determined to 0.2 mg/kg. Cytokine release syndrome (CRS) was the most common adverse event. Grade 3–4 toxicities were however not related to CRS but rather to hematological and hepatic toxicity. << >> This is not surprising as the naturally occurring CD40 activation is mediated via trimer CD40L. << (Didn't know that!) >> An example of a second-generation anti-CD40 agonistic antibody with improved Fc?RIIb cross-linking capacity is Apexigen’s APX005M, a humanized IgG1 antibody with the S267E mutation that improves FcgRIIb and abrogates FcgRIIa interactions. This antibody also blocks the natural CD40/CD40L interaction [14]. The antibody has now reached phase II studies. << (and a reminder......) celldex.com >> 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. <<

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