There's a difference between novel, unexpected safety issues specific to ZEN-3694 and expected adverse drug side effects that seem to commonly occur with many pan-BET inhibitors. Remember, Zenith increased the dosing level until they reached the maximally tolerated dose (MTD), which was arrived when they observed greater than 2 out of 6 patients with dose-limiting toxicities (DLTs). So in the process of finding the MTD, adverse drug effects/toxicites are found.

DLTs have occurred....that's the point of Phase 1 dose escalation. What are the DLTs? Are they the same DLTs observed with other pan-BET inhibitors? Are they able to achieve efficacy at doses that don't elicit DLTs, or does the efficacious dose always come with some adverse events? How is ZEN-3694 differentiated from other pan-BET inhibitors.

We were told that ZEN-3694 has an on-target safety profile. What does that mean? To me, it could mean that it was just as safe as other previously examined pan-BET inhibitors, which does not mean that ZEN-3694 is w/o adverse side effects. If there were no adverse side effects with everyday/once a day dosing, why are they currently exploring an intermittent dosing schedule as the last part of their Phase 1? To me, I am still looking for Zenith to disclose and concrete info that indicates that their pan-BET inhibitor is any more efficacious w/o side effects of other pan-BET inhibitors in current trials.

BearDownAZ