Tada,

A few comments and corrections:

Timeline for futility analysis (125 MACE events): In March 2016 at the Q1 webcast, Mike Sweeney indicated that the 125 MACE event target for the futility analysis would be reached by mid 2017. In Fall 2016 at the R&D day, McCaffrey said H1 2016 and Sweeney said H2 2016 for the futility analysis.

Timeline for 250 MACE events (end of trial*): In March 2016, Sweeney indicated that the 250 MACE event target for BETonMACE was anticipated to be reached by mid 2018. Although at the recent corporate update in December 2016, McCaffrey indicated that recruitment was a little behind, he also indicated that sites were being added in Russia (20 sites, 200 patients) that will be paid for by the contract research organization. So although recruitment might be transiently running behind schedule, the addition of Russia sites may put it back on track. If they reach 250 events by mid-2018 and don't need to adjust the event target to 375 (see below), I find it highly unlikely that announcement of top-line results would be delayed into 2019.

*Number of events for end of trial: In March 2016, Sweeney indicated that there will be a sample size estimate analysis at 175 MACE events at which time the trial could be adjusted to continue until 375 MACE events. Tada, you made a statement "assumes that if RRR is between 25% and 30% an additional 1200 patient recruits will be required and adding approximately one year to the BETonMACE trial timeline." Was your statement related to your understanding of how the company interprets its 125 or 175 event futility or sample size estimate analysis, respectively? I've never read or heard the company make a statement similar to yours.

What %RRR is required for success?: Tada made a statement "assumes that if we don’t reach at least 25% RRR this lottery ticket just turned into trash." I don't agree with this at all. What basis do you have saying that a %RRR of less than 25% for 3-point MACE wouldn't be a success? In the context of %RRR for 3-point MACE acheived by recent MACE diabetes trials with SGLT2 inhibitors (Jaridance; empagliflozin) or GLP-1 receptor agonists (Victoza; Liraglutide), which both were in the "teens" for %RRR for 3-point MACE and were deemed HIGHLY SUCCESSFUL, why would you say that a less than 25% RRR in BETonMACE would be a failure?