Sartorius #2 eBook - 2019 - 8

Importance of mAb Discovery and Development in Immunotherapy

"We need to somehow mitigate the toxicity of these T-cell engagers," insists
Schellenberger. "If you have a protein-based drug, then you could give it right away,
instead of after the several weeks it takes to develop an individualized CAR T-cell
therapy; that would be a big benefit to the patient."
Amunix has developed a new format of bispecific T-cell engagers that can be delivered
in a low dose with lower toxicity using XTEN technology, an alternative to PEGylation.
"The T-cell engager," Schellenberger explains, "works like an adaptor molecule. It
bridges the tumor and the T cell." XTEN is a protein polymer that is engineered to
behave like polyethylene glycol (PEG) which is attached to bsAbs to increase their
half-life in vivo without the need for an Fc domain.
"XTEN has evolved into kind of a Lego kit for pharmaceuticals," Schellenberger notes.
"It allows us to make very complex molecules which by other means we just couldn't
produce."
The company's lead XTENylated bsAb, AMX-268, is in preclinical development. It is
a T-cell engager that binds to CD3, a T-cell receptor (TCR), and EpCAM, an adhesion
molecule overexpressed in 80% of solid tumors.

"We give the drug in an inactive form and convert it to the active form only when it is
in the tumor environment," Schellenberger says. The company's pro-drug (AMX-268)
is activated by the inflammatory process found primarily within the tumor microenvironment, reducing off-target toxicity and increasing antitumor selectivity, "so that if
our molecule finds that target in a healthy organ, it will still leave it alone."
The active form of the drug is smaller than typical Fc-containing intact antibodies,
allowing it to be removed easily and rapidly through the kidney. Schellenberger's data
suggests that AMX-268 may have lower immunogenicity and a lower toxicity profile
among other potential EpCAM-targeting T-cell engagers such as Removab (Fresenius
Biotech) and the investigational MT110 (Amgen).

8 |

GENengnews.com

Amunix has used its XTEN platform to develop protease triggered immune activator (ProTIA)
molecules. These are bispecific T-cell activators that are designed to outperform other
bispecific formats with respect to characteristics such as half-life and safety. An early ProTIA
prototype molecule, one that incorporated Amgen's MT110, allowed Amunix to demonstrate
the ProTIA format's advantages. Amunix is now replacing the Amgen-specific portions of the
prototype to generate additional ProTIA molecules.

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Sartorius #2 eBook - 2019

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