Just a few notes from the Zenith webcast yesterday. I wasn't there for the Q&A, so if anyone else has some info from the Q&A please share! Thanks!

Phase 1 ZEN-3694 single agent trial is done now. Nothing really new reported here.

ER-positive breast cancer trial is their next program, but no details shared.

Phase 1 ZEN-3694/enzalutamide combo trial still ongoing.  I was very happy to hear that they are able to do continuous (every day) dosing without having to take a "drug holiday" aka intemittent dosing as required by many if not all other companies with pan-BET inhibitors. All four cohorts are doing every day dosing. This is huge. Also, DM mentioned that in combo with enzalutamide, they are able to use doses of ZEN-3694 higher than the maximum tolerated dose arrived at in the single agent ZEN-3694 trial.

Why do only some patients respond in the combo trial (i.e. why do some have progression and others not)? They have an extensive translational medicine plan for deciphering the MOA and for designing future biomarker driven trials using information from whole blood and tumor biopsy. See slide 19. Stay tuned.

Based on my estimates the data shown yesterday (slides 17 and 18 summarized below) is ~5 weeks outdated so if these patients have not progressed one could add ~5 weeks to their status for the progression free survival graphs.

Dose 1 (1X): all 3 patients now progressed. Longest patient in first dose went to ~45 weeks w/o progression.

Dose 2 (1.33 X): 2 of the 6 patients had progression at 10 or 11 weeks. 3 of the 6 patients still progression free and are at 33-36 weeks. 1 of 6 patients is progression free at ~ week 12. PSA data on the 3 rock star cohort 2 patients now shows flatlined PSA through 28-32 weeks.

Dose 3 (1.66X): 2 of 4 patients progressed at 10 or 11 weeks. 1 patient is progression free at 15 weeks and another patient just started in trial.

Dose 4 (2X): 3 patients ongoing at 4-8 weeks in trial.

Slides 21 to 23 were very informative and encouraging. On big problem with pan-BET inhibitors is the side effecct of grade 3-4 adverse events. Great to hear that they are seeing no grade 3 or 4 adverse events at efficacious doses.

Slide 23 was one of my favorites yesterday. A great summary of how ZEN-3694 is superior to other pan-BET inhibitors.

Lack of thrombocytopenia: Can be dosed without dose interruption, other BETi have intermittent schedule (2 weeks on / 1-2 weeks off) that can effect efficacy

Very low GI event frequency: Good drug compliance

On target tox profile: MTD will not be limited by off target tox, on target tox (low grade GI events) are very manageable through PRN use of anti-emetics and hydration

No interaction with enzalutamide: Dose adjustment will not be needed for individual patients, reduces variability

Well characterized PK/PD: Dose dependent exposure, low variability;  Good half life, target modulated for sufficient duration with QD dosing; Exposures are at levels that have shown efficacy in pre-clinical models; Very well characterized PK/PD correlation to guide selection of RP2D

BearDownAZ