[Free Content] TGTX in Pictures

 

TG Therapeutics has two programs, the CD20 targeting antibody TG-1101, and PI3K delta inhibitor TGR-1202. The focus of this post is on TGR-1202. Earlier coverage can be found here [link].

TG has been hesitant in giving out the structure of TGR-1202. It’s out now, so here it is below along with Idelalisib and IPI-145 (left to right) for comparison.

TGTX structureIdelalisib StrutureIPI-145 Structure

 

 

 

 

 

IPI-145 is nearly identical to Idelalisib while the TG compound has a few additional modifications, likely accounting for its different behavior. Differences in PK have been commented on previously, so they won’t be covered much here.

Seeing data being presented on TGR-1202 has been like watching a slow-motion video of Idelalisib or IPI-145 in action. One and a half years after trial initiation and following dose escalation to greater than 800 mg QD, it appears TGR-1202 is showing definitive activity in CLL through what TG calls a “Delta-like” manner.
TGTX 800mg

Notice that while responses in CLL are now apparent, TGR-1202 oddly fails to demonstrate substantial activity in iNHL (orange bars) and MCL (purple bars)- both of which are known to be susceptible to PI3k delta inhibition.

Below are waterfall charts from Idelalisib in iNHL:
Idelalisib iNHL
And MCL:
Idelalisib MCL

 

 

 

 

 

 

 

 
Data are similar with IPI-145.

In a company presentation, TG attempts to explain the lower than expected activity. Previous high doses are now considered the the “bottom end of range for projected clinical efficacy.”

Screen Shot 2014-10-20 at 6.02.12 PM

 

But this chart is a complete fraud. Based on my calculations (assuming a MW of 500 for TRG-1202), TG is comparing the Cmax of Idelalisib and IPI-145 to what appears to be the Ctrough of TGR-1202.

TGTX PK

 

Disclosure: Author is Long GILD

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