Thanks to Kelsee for posting these portions of Friday's MD&A. Between statements made in the MD&A and statements from Masila's transcript of the June 30th special meeting, things still look in tip top shape.

From Masila's transcript: "Resverlogix still in active discussions with FDA for the Phase III trial in US. Just takes a while to get everything done. Still positive on everything moving ahead, although I got the impression we might see things moving forward in China and Europe a bit more quickly. Looking at moving to a different department at FDA to make things move faster, so instead of endocrine and metabolic, it might be cardio and renal"

Also from Masila's transcript: "A bit of change in plans around the trial. Will now include both atorvastatin and rosuvastatin users so that they can get further understandings on why it works well with one and not the other. Anywhere from 2400-4800 patients, dosing up to 2 yrs with average of 18 months. 250 of those likely in China territories with funding provided by Shenzen. They basically want to run only 1 Phase III trial instead of FDA coming back and asking why lipitor users don't benefit as much and making them do another IIb."

From the MD&A: "(W)e expect to launch the upcoming BETonMACE Phase 3 clinical trial in the fall of 2015. BETonMACE will be a double-blind, placebo-controlled, 2 arm parallel-group (allocation ratio 1:1), study of RVX-208 at a dose of 100 mg b.i.d. (total daily dose of 200 mg) or matching placebo in combination with standard of care high potency statin therapy administered to type 2 diabetes mellitus (“T2DM”) subjects with history of recent CVD event and HDL-C level <40 mg/dL males or <45 mg/dL females. Standard of care high potency statin therapy shall consist of daily dose of either atorvastatin 20-40 mg or rosuvastatin 10-20 mg. After an initial screening period of 1 to 2 weeks during which subjects will be treated with standard of care high potency statin therapy, subjects will be randomized to either RVX-208 100 mg b.i.d. or matching placebo with continued statin treatment. This combination treatment period will continue for up to 104 weeks. The primary endpoint of the BETonMACE trial is designed to show a RRR of MACE, narrowly defined as a single composite endpoint of CV Death or Non-fatal MI or Stroke, in high-risk cardiovascular and DM patients, as we have seen in previous Phase 2 clinical trials with RVX-208. The study is an event-based trial and will continue until 250 MACE events, defined as CV death, non-fatal MI and stroke, have occurred. MACE will be adjudicated by an independent Endpoint Adjudication Committee and the study will be monitored by a Data Safety Monitoring Board."

So sounds like 2400 to 4800 patients; half statin-only (rosuvastatin or atorvastatin) and half RVX-208 plus statin (rosuvastatin or atorvastatin). My interpretation is that 1 arm of the 2-arm parallel group is statin-only (rosuvastatin or atorvastatin) and the other arm is RVX-208 plus statin (rosuvastatin or atorvastatin). So at minimum, we are looking at 2400 patients. Of these 2400, 1200 would be statin-only (rosuvastatin or atorvastatin) and the other 1200 would be RVX-208 plus statin (rosuvastatin or atorvastatin). However, it is unclear if the trial is designed to enroll a set number of patients for each statin group. I'll assume here that they are shooting for equal numbers of atorvastatin and rosuvastatin patients. In which case, we should expect a minumum of 600 patients receiving RVX-208 + rosuvastatin and 600 patients receiving RVX-208 plus atorvastatin.

Now let's tie this into the MACE observations from the post-hoc analysis of the combined SUSTAIN and ASSURE trials. My numbers are taken from the slides I downloaded for Jan Johansson's ESC 2014 presentation. MACE were observed in 17/168 (10.1%) of statin-only patients and 18/331 (5.7%) of RVX-208 + statin patients. As far as I know, we do not know the split MACE data for rosuvastatin vs. atorvastatin. These numbers are for all patient and are MACE over 6 months. In those with diabetes (which will comprise all of the BETonMACE patient population), the MACE were observed in 13.8% of statin only vs. 3.9% of RVX -208+ statin, again this is over a 6 month period.

So let's put this into the context of BETonMACE. In BETonMACE, there will be equal numbers of statin only vs. statin + RVX-208, whereas in the combined SUSTAIN/ASSURE data, 1/3 of total patients were statin only and 2/3 were statin + RVX-208. BETonMACE is an event-driven trial that seeks to have a minimum of 250 MACE events. Let's assume that they will enroll and start dosing 1200 patients by start of Q1 2016, 1200 patients by start of Q2 2016 and 1200 patients by start of Q3 2016. Let's also assume that the 13.8% and 3.9% MACE occurrence for statin only and RVX-208 + statin, respectively, hold true for the first 6 months of treatment. For the group starting at the beginning of Q1 2016, we might expect 83 of the first 600 statin only and 23 of the first 600 RVX-208 + statin patients to have experienced a MACE event in their first 6 months of treatment so at the end of Q2 2016 there will already have been a total of 106 MACE events. Apply this same logic to the group starting treatment at the beginning of Q2 2016 and by the end of Q3 2016 we would expect these 600 statin-only and 600 RVX-208 + statin patients to contribute another 83 and 23 patients, respectively, to have experienced a MACE event. Just considering this first group of 2400 patients, by the end of Q3 2016 we would expect to have a total of 212 MACE events based upon the MACE incidence observed in the SUSTAIN/ASSURE diabetic population. That's already 212 of the 250 required MACE events!

Keep in mind that by the end of Q3 2016, the first group (that started in Q1 2016) will now be at 9-months treatment and that a third group of 1200 patients will be 3 months into their treatment. So it is reasonable to assume that an additional 38 MACE events will have occurred between months 6 and 9 of treatment group 1 and between months 0 and 3 of treatment group 3, likely bringing the total MACE to 250 by the end of Q3 2016.

Of course there are a lot of assumptions here. But based on the information available, that sounds pretty good!

Also, we still need to hear more details about the chronic kidney disease sub-aim of this trial.

Feel free to chime in with any refinements to my assumptions. For example patient enrollment may take a lot longer that I am assuming, which may push things back a few months or so.

Best,

BearDownAZ