Great presentation. I can tell they put some great effort into clarifying several issues. BETonMACE enrollment is complete with readout early 2019 (Q1 2019). Slide 14 still shows up to 104 week duration of treatment; however slide 16 indicates average treatment duration of 22-24 months. I am concluding that slide 14 is incorrect.  

Slide 17 was the money shot and answered most of my questions sufficiently. Kudos to management for providing so much information.

Here is the text from slide 17, followed by my original questions and my notes:

1) Maintain existing safety profile until trial completion, last dosing still expected in late 2018

2) Adaptive trial options –stop dosing at 230-235 events and wait for 250 events or stop at 250 events and  probably accumulate 270+ events? 

3) Futility analysis vs. SSRA?  Neither appear to offer any trial benefit at this point. Both cause a statistical penalty against final powering.  For now we have chosen neither.

4) Three point MACE event accumulation now stands around 200 with an occurrence rate of 10-15 per month 

5) Adjudication of all 270 SAE MACE events will take two months post trial completion 

6) Top line data will be announced immediately upon adjudication completion.  Key secondary  end points will also be released  if available –Renal & Cognitive function

7) Throughout 2019 full outcomes, pre-specified endpoint data, safety results, and clinical implications will be reported and published

Here were my original questions and I have noted whether they were addressed.

1) The obvious one....details on the plan/status of the SSRA. Is it still planned? Have 75% of planned events (188 events) been adjudicated yet? Will the SSRA plan be abandoned akin to what happened with the planned futility analysis at 50% of planned events (125 events) that never occurred?

 Answered

2) Related....will the company provide updates as the # of events approaches 250 and when the last patient study site visit has occurred. How long is the adjudication process taking after a suspected 3-point MACE event has occurred? The ongoing (and soon to be reporting top-line data) REDUCE-IT trial by Amarin (discussed here) provided these types of updates. Will Resverlogix?

More or less answered.

3) Another obvious one.....is top-line data still expected by end of 2018, or is the revised target for top-line data now 2019?

Answered

4) I would appreciate an explicit statement that BETonMACE protcol is amended to allow for patients to be dosed beyong 104 weeks. There has been no official statement from the company on this and the ClinicalTrials.gov listing is outdated (last update 9/27/17) and does not reflect this. If I recall, the only items that have mentioned this so far are the AAIC and ERA-EDTA posters for the cognition and renal sub-studies, respectively, that indicated that at completion patients will have been dosed for between 6 and approximately 36 months. 

Not explicitly answered. Still ambiguous

5) Revised timeline for start of Fabry disease, Renal/dialysis and pulmonary arterial hypertension (PAH) trials that are listed on ClinicalTrials.gov. The PAH trial was just listed and has an estimated start date of November 2018. The Renal trial estimated start date has been revised a few times and the last one is now outdated and lists estimated start date of July 2015. The Fabry trial estimated start date has also been revised previously, but currently lists estimated start date of Sept 30, 2018.

Mostly answered. Some ambiguity. New timelines posted on Slide 5 for various trials. BETonMACE expected to readout Q1 '19. On Slide 5, all of the non-BETonMACE trials seem to indicate Phase 2. CKD trial expected to start Q1 '19 with readout Q4 '19. I'm not sure if this is the Phase 1/2 renal/dialysis trial currently listed on ClinicalTrials.gov or a different one. Later in the presentation it refers to BETonCKD Phase 2b/3 trial. Need clarification here. Fabry disease trial expected to start Q4 '18 with readout Q4 '19. PAH trial expected to start Q3 '19 (not November '18 as listed on ClinicalTrials.gov) with readout Q2 '20. Vascular cognitive dementia expected to start Q2 '19 with readout Q2 '20. 

6) Have any US patients been enrolled in BETonMACE or has Resverlogix made the decision to not enroll any US patients in BETonMACE?

Not answered in slides, but I assume no US patients.

7) Does Resverlogix expect the top-line data announcement to only provide guidance on the primary outcome (time to first occurence to 3-point MACE), or will this top-line data announcment also contain guidance on the renal and cognition sub-studies. If the sub-studies are not included in this first top-line data announcement, when will they be announced (at BETonMACE full data presentation? As another top-line data announcment?

Answered