>> Regards the 158F-negative...stopped following MGNX, is that for gastric trial? <<
Sorry, had to run out the door. I know that you know this story better than me!
First, "158-negative" as in "they don't carry the CD16a158 allele". The 158-positive population was a pre-specified subgroup in SOPHIA.
CD16a is the low affinity Fc receptor, and margetuximab was Fc-engineered for enhanced affinity with CD16.
The epitopes recognized by marg and trastuzumab are at least overlapping. So it's a very big hurdle, getting marg to work in trastuzumab refractory patients. But it does. Big contribution to science, regardless of commercial value of the antibody.
So, CD16a is expressed on cells of the innate immune system, including NK cells. Marg has ADCC activity. Furthermore, the Fc optimization includes reduced affinity for Fc receptors, the activation of which inhibits innate responses.
ncbi.nlm.nih.gov
I personally believe that marg would beat trastuzumab by wide margin in naive patients, and that, if approved, it can be cautiously tested in earlier stage patients. I'd vote to approve it in a heartbeat.
And the design of the gastric trial, colaborator Zai Lab, is pure genius. Macrogenics is out on the "first innovator" limb with marg. Early leaders often get bogged down in stuff where the need has passed. Koenig draws flack, but I admire the guy. |
