Replies to post #210062 on Biotech Values

[genisi]

I-O MoAs

To put in a bit more scientific way: anti-CTLA-4 works in early-phase T-cell response (priming phase in the lymph nodes) and anti-PD-(L)1 affects the later stages of T-cell immune response (at the effector phase in the lymph nodes and tumor microenvironment).

[JohnWayne]

Yes, in effect that's what my 2nd answer was saying, though not in the same words.

I'd submit that the more interesting dosing for a CTLA-4 combo is not treme in MYSTIC -- which follows the traditional "up to 4 doses" schedule that is standard for CTLA-4 inhibitors; in effect, AZN isn't doing anything out of the ordinary with using only 4 doses of treme in MYSTIC -- but is Yervoy in CheckMate 227.

As you alluded to (which I didn't realize) Yervoy appears to be dosed continuously, every 6 weeks. Seems to suggest that BMY thinks you may need to "re-release" the brake for 1L NSCLC, though less frequently and with less intensity (i.e. lower dose) than for CTLA-4 in other tumor types.

We should have the answer to which approach is better fairly soon, but it seems like BMY has generated more robust Phase 1 data to inform its Phase 3 design. If I was invested in AZN, I would definitely be worried about MYSTIC...