ARTICLE | Product R&D

TGN1412: The next generation

CD28 superagonist TGN1412 returns to the clinic as TAB08, with lessons in tow

November 5, 2015 8:00 AM UTC

A compound whose catastrophic Phase I trial shook the drug development world in 2006 made it through Phase Ia testing without adverse effects in 2013, and is now in Phase Ib/IIa testing in rheumatoid arthritis (RA). The almost decade-long journey of TGN1412 back to the clinic - now rebranded TAB08 and developed by Russian biotech TheraMAB LLC - highlights how oversimplified preclinical assays create risks that could be avoided by investing time in rigorous pharmacology on detailed parameters, such as receptor occupancy across different species.

TAB08 is a mAb that stimulates CD28, a cell surface receptor expressed at high levels on immune suppressive Tregs but at lower levels on conventional T cells. In both cell types, CD28 is a costimulatory receptor whose activity enhances antigen signaling by the primary TCR, with which it typically needs to partner for T cell activation. But as a superagonist, TAB08 induces CD28 signals that are potent enough to activate T cells in the absence of strong TCR cues. ...