Molecular Templates has created vast libraries of ETBs by embedding random targeting domains into bacterial toxin scaffolds.  Each ETB has a distinct binding affinity but retains the biologically active properties of the parent toxin.  ETBs are capable of targeting validated therapeutic cell surface receptors but also non-traditional targets that cannot be therapeutically targeted by antibodies or small molecules.  

Molecular Templates has successfully developed a lead ETB (MTI-SAM3) against an undisclosed receptor present on certain melanoma cells.   MTI-SAM3 exhibits an LD50 in the nM concentration range against melanoma cells but is inactive against cells of other etiologies.  MTI-SAM3 retains the predictable PK/PD profile of the parent toxin and was discovered through an etiology-based screen in which the target was not specified.  Molecular Templates anticipates entering clinical studies with MTI-SAM3 in the near future.



  Antibodies Immunotoxins ETBs
Screening Metric Binding affinity Binding affinity of targeting domain Direct cell-kill  [a]
Target ID a priori Required Required Not required  [b]
Mechanism of Action Target binding Direct cell-kill Direct cell-kill
Target Specificity Very high (nM to pM) High (nM) High (nM)   [c]
Size ~150 kd ~60 kd ~20kd
Half-Life Days to weeks Minutes to days Minutes to days   [d]
PK/PD Established Established Established   [e]
Other Scaffold Properties Receptor mediated internalization Forced internalization; Intracellular routing Forced internalization; Intracellular routing; Antigen presentation


[a]  ETBs are screened on cell-killing ability that involves its ability to bind a target, internalize, and route itself intracellularly.
[b]  Because ETBs are selected on cell-kill, etiology based screens can be performed without knowing the target beforehand.
[c]   A different standard applies to ETBs given their unique features and high affinity does not correlate to cell kill specificity or potency.
[d]   ETBs can be manipulated to extend half life in the event it is optimal for particular disease indications.
[e]   ETBs share the same pharmcokinetic and pharmacodyanmics as the parent toxin scaffold making them predictable.

©2010 Molecular Templates Inc.