From what I understand, patients in the De Bono JS et al study had progressive mCRPC disease at study entry AND ≥ 24 weeks of Abiraterone treatment (median duration of previous Abiraterone therapy was 54 weeks). The ZEN-3694/enzalutamide combo trial required disease progression after previous Abiraterone or Enzalutamide therapy. However, as shown on slide 14 of the BioEurope presentation, most of these patients shown treated with ZEN-3694/enzalutamide were previously on Abiraterone (including the 3 rock stars). So both the De Bono JS et al study and the Zenith trial (most of the patients so far) required prior progression on Abiraterone. It will be interesting to see the data unfold for the ZEN-3694/Enzalutamide treatment in those that progressed on Enzalutamide as the trial continues. 

Importantly, in the De Bono JS et al study, 46% of patients received Enzalutamide treatment for at least 6 months; 30% for at least 9 months and 16% for at least 12 months. And in PSA responders, the median Enzalutamide treatment was 12 months. Median radiographic progression free survival (rPFS) was 8.1 months in the total population. Our 3 rock star Zenith patients that may be at about 1 year rPFS now look great by themselves. However, in the context of the De Bono JS et al study and in the context of the other patients in the Zenith combo trial that made it 20 weeks or less (slide 14 Bio-Europe) before radiographic progression, our 3 rock stars might just be on par with the number expected to go that far with Enzalutamide alone in the De Bono JS et al study. There is too small of a patient population/too few observations in the Zenith trial to read too much yet. The "target" line in Bio-Europe slide 14 is ~8 month or 32 weeks. How can this ~8 months be the target of the ZEN-3694/Enzalutamide combo therapy if Enzalutamide alone elicits a median 8.1 months rPFS in the De Bono JS et al study? Shouldn't the combo target be beyond that expected w/ Enzalutamide alone in the De Bono JS et al study?

For the PSA data, Zenith has so far shown only a select # of patients. Slide 13 of BIO-Europe shows 3 patients from cohort 2 (rock stars), 1 patient from cohort 1 and 1 patient from cohort 3. Where are the other patients' PSA data? Without seeing the other patients, only focusing on the 3 rock stars seems like cherry-picking. The 3 rock stars had a very robust >80% decrease (the other two didn't seem to decrease but were just stabilized). That's great! But about 16% of the patients on Enzalutamide alone had that kind of >80% PSA decrease (see waterfall plot Fig 3 in the De Bono JS et al study). I don't know at what point in the De Bono JS et al study that the PSA measurements were made. So the duration of PSA suppression may be a key difference between the two studies. Regardless, it is only 3 patients from the Zenith trial that we are seeing data for robust PSA decrease and we don't know about the PSA numbers in the total Zenith combo trial population. Long story short, tough to say if those 3 rock stars are doing so good because of the combo, or if just by chance one would expect a certain % of patients w/ enzalutamide alone to respond similarly.