"Can someone give me a (brief) summary of what we are still waiting to be revealed from BoM?"

I can give you a summary, but it won't be brief!

1) Cognition sub-study data (see poster and slides linked below) looking at MoCA cognition test changes from baseline in those patients in BETonMACE 70 years and older (469 patients, or about 20% of total BETonMACE patients). MoCA test is administered at baseline and annually and at the end of the trial. Subgroups of patients with MoCA score <26 and <21 at baseline  will also be analyzed separately from the total 469 set of patients.

https://www.resverlogix.com/upload/media_element/173/b9738b92dd21/2019-07-08---aaic-poster-2019-final.pdf

https://www.resverlogix.com/upload/event/42/4388386bbd26/2019-03-29---ad-pd-2019-cummings-final.pdf

Cognition sub-study will be presented at CTAD on December 5th.

Clinical Trials on Alzheimer's Disease (CTAD): December 4-7, 2019; San Diego, CA. Two presentations in the final program on Thursday Dec 5th during the symposium on "Epigenetics and the BET-system in vascular dementia, Alzheimer’s disease and mixed dementia – the problem and potential remedies." 

PRESENTER 3: The epigenetic inhibitor APABETALONE corrects pathophysiological brain endothelial and microglial cell activation that contributes to neurodegenerative disease Ewelina Kulikowski, SVP Research and Development, Resverlogix Corporation, Calgary, Canada

PRESENTER 4: Epigenetics, the BET-system, Alzheimer’s Disease and Vascular Cognitive Impairment; The BETonMACE study and effects of apabetalone 100 mg b.i.d. two years treatment on cognition in diabetes patients with established cardiovascular disease Jeffrey Cummings, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA

2) CKD sub-study data (see poster linked below). In this population of 259 patients with baseline eGFR<60 (in which we already know there was a 50% RRR for 3-point MACE) eGFR is evaluated at screening, 24 weeks, 52 weeks, 76 weeks, 100 weeks and at the termination of the trial. Markers of kidney disease risk such as alkaline phosphatase, serum chemistry markers and inflammatory markers will also be included in the analysis. 

https://www.resverlogix.com/upload/media_element/125/20402f6425eb/2018-05-02-era-edta-poster-2018-kidney-disease-subgroup.pdf

CEO Don McCaffrey said in the webcast on Monday that the CTAD is the only embargo left. No guarantee, but this implies that CKD sub-study data is either no currently under embargo and could be announced anytime, or that it is related to the CTDA Dec 5 embargo.

".....there have been several posts referencing eGFR data, and I'm confused why that is not currently available.  Are these plausibly linked?"

YES! Looks like someone has been sleeping during class! Just kidding. The relationship amongst alkaline phosphatase, cardiovascular disease, renal function and cognition has been the big push with recent presentations at ASN and AHA. See the posters linked below. You can read more about the relationship between apabetalone and alkaline phosphatase in this post. 

ALP Levels Predict Adverse Cardiovascular Outcomes and Cognitive Impairment in High Risk Patients - AHA 2019 Poster

Association of Serum Alkaline Phosphatase with CKD and Cognitive Function in Patients with Diabetes and Acute Coronary Syndrome - ASN 2019 Poster

Apabetalone Lowers Serum Alkaline Phosphatase in CVD Patients With and Without CKD and Improves Cardiovascular Risk - ASN 2019 Poster

Apabetalone Downregulates Alkaline Phosphatase and Improves Cardiovascular Risk - ASN 2019 Poster

A lot of overlap between the aged (70 or older), cognitively impaired (MoCA<26) and CKD (eGFR<60) populations in BETonMACE. The cognition subgroup is significantly older and has significantly lower eGFR compared to the total population. The CKD subgroup is significantly older than the non-CKD subgroup and is enriched in cognitively impaired patients. I detail this further in this post. 

"given that whatever promising data is revealed it is likely to be just as underpowered as the other sub-group info already at hand, right?"

The other sub-group data has not been underpowered for detection of statistical significance. However, when a primary endpoint fails, all subsequent secondary and exploratory endpoints are considered only exploratory and not confirmatory results even if they achieve statistical significance. 

Perhaps the most exciting result from BETonMACE thus far is the observation that nearly all of the apabetalone benefit occurred in the CKD subgroup. So clearly, this is a super responder population. Therefore, we know apabetalone is working here. If the previous Phase 2 data hold up, then we should see significant eGFR improvement and even more pronounced alkaline phosphatase decrease in this population (compared to the for modest and statistically significant alk phos lowering in the total population).

Jonzobot posted "A few possibilities, I guess:

1. The eGFR numbers did not show a trend (or a near-enough statistically significant trend) for the low eGFR group;
2. The eGFR trend data is linked to the VD data somehow (perhaps those with VD benefitted with highly correlated changes in both eGFR and MOCA?) and this may therefore still be under embargo;
3. The data is not yet analyzed (not likely given it was prespecified);
4. The eGFR numbers did show a trend in a non-prespecified subgroup but if that's the case we probably don't yet know and that analysis has yet to be started/completed.
5. The data is analyzed and ready, and did find a trend, but has not been released for unknown reasons."

Just to clarify, many define a trend as a p-value >0.05 but less than 0.1. Not quite strong enough to say statistically significant by the p<0.05 cut-off, but still encouraging. I interpret your use of trend above as statistical significance.

As for those scenarios above, my guess is #2 or #5. I find it extremely unlikely in #3 that the data isn't analyzed yet. Based on the incredible 50% RRR in the CKD sub-group for 3-point MACE suggesting that the drug is working incredibly well in CKD patients, I also would be very surprised if the eGFR changes in this subgroup were not significant (#1 above). I'm not quite sure what you mean in #4. The stage 3 CKD subgroup of patients w/ baseline eGFR below 60 was pre-specified. Perhaps you mean a group not pre-specified like stage 2 CKD with eGFR between 60 and 89. 

My hunch is that #2 is correct. There is quite an overlap in the patient population for the CKD and cognition subgroups, and there is a relationship between alk phos, CVD, CKD and cognition as described above. For this reason, I think that the CKD eGFR data is being kept quiet for now in order to deliver a very exciting story at CTAD on Dec 5.

BDAZ