arGEN-X reveals the target and unique mechanism of action of its most advanced preclinical antibody at the PEGS Summit 2012
November 06, 2012
- ARGX-110 is highly potent and selective for CD70, a key target in cancer and autoimmune diseases
Breda, the Netherlands and Ghent, Belgium – arGEN-X, a biopharmaceutical company focused on the discovery and development of human monoclonal antibodies from its proprietary SIMPLE Antibody™ platform, will disclose the exciting attributes of its most advanced SIMPLE Antibody™ candidate, ARGX-110, at the PEGS Summit, Nov 6-8, 2012 in Vienna, Austria. The exciting potential of ARGX-110 will be presented by Dr Karen Silence, Research Fellow and ARGX-110 project leader.
ARGX-110 is a novel, fully human antibody having two independent modes of action. It selectively targets and neutralizes CD70, the ligand of CD27, as well as depletes CD70 over-expressing cells. In normal tissues, expression of CD70 is transient and restricted to activated B- and T- cells and mature dendritic cells. However chronic expression of CD70 on T cells is a hallmark of many autoimmune indications, causing constitutive T- and B- cell activation and eventual disease pathology. Overexpression of CD70 has also been documented in a variety of solid and hematological tumors, where it is thought to play a role in escape from immune surveillance and tumor cell proliferation and survival [Boursalian TE, McEarchern JA, Law CL, Grewal IS (2009) Adv Exp Med Biol. (2009) 647:108-19].
arGEN-X scientists carried out a detailed characterization of ARGX-110 to support its clinical development for the treatment of cancer and autoimmune disease. ARGX-110 binds to human and non-human primate CD70 with picomolar affinity. It specifically inhibits CD70/CD27-induced signalling in a dose-dependent fashion, a mode of action which is believed to result in inhibition of proliferation and survival of tumor cells and potentially could lead to re-activation of the patient’s anti-tumor immune responses. ARGX-110 is potently cytotoxic for CD70 over-expressing cells by virtue of enhanced antibody dependent cellular cytotoxicity (ADCC).
ARGX-110 has demonstrated a promising in vivo efficacy and safety profile and is predicted to have a half life in humans of around 23 days. As a result of these findings, arGEN-X has designed a European Phase I study in patients with CD70 positive malignancies to start early in 2013.
Commenting on today’s announcement, Prof. Hans De Haard, CSO of arGEN-X, said:
“This presentation on ARGX-110 reveals the novel attributes of this therapeutic antibody, which has the potential to become a best-in-class treatment in both cancer and autoimmune diseases. We are extremely pleased at the speed with which we have validated and advanced ARGX-110 and are looking forward to starting our Phase I study in early 2013. The success of this program to date underscores our ability to consistently generate diverse antibodies with exceptional potencies and unique properties from our unique SIMPLE Antibody™ platform. We believe that ARGX-110 will be an important driver in our company becoming a key player in the antibody space.”
ARGX-110 was selected from more than 30 unique, potent, CD70-specific candidates generated from the SIMPLE Antibody™ platform. ARGX-110 has other important characteristics as a development candidate: Its sequence composition is 99% homologous to human and therefore it is expected to have a favorable immunogenicity profile. Further, expression studies indicate that ARGX-110 is manufactured at consistently high quality, yield and stability.
ARGX-110 is the most advanced of five therapeutic programs generated using the SIMPLE Antibody™ platform. Four of these are are under development at arGEN-X while the fifth, ARGX-109, is is being developed by its partner RuiYi (formerly Anaphore).
arGEN-X’ SIMPLE Antibody™ Platform is based on the active immunization of outbred Camelids to deliver antibodies whose variable regions are virtually identical to those of human antibodies. These variable domains are recombined with human antibody constant domains to generate full size, fully human therapeutic antibodies.
SIMPLE Antibodies exhibit gold-standard potencies and manufacturability without the need for additional engineering, making them ideal candidates for development as therapeutic antibodies.