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Message: BETonMACE Prespecified Cognition Assessment Results - Post-CTAD Conference Call - Transcript - 191206
BETonMACE Prespecified Cognition Assessment Results
Resverlogix Conference Call and Webcast, December 06, 2019
Thank you for standing by. This is the conference operator. Welcome to the Resverlogix conference call and webcast to present BETonMACE Prespecified Cognition Assessment Results. As a reminder, all participants are in listen-only mode, and the conference is being recorded. Should you need assistance during the conference call, you may signal an operator by pressing * and 0 (star and zero). I would now like to turn the conference over to Mr. Donald McCaffrey, President and Chief Executive Officer of Resverlogix Corp. Please go ahead.
Dr. Donald McCaffrey:
Slide 1 – BETonMACE Prespecified Cognition Assessment Results, December 6th 2019 (Title Slide):
Welcome to the BETonMACE Prespecified Cognitive Assessment Results. My name is Donald McCaffrey, CEO of Resverlogix. Today we’ll be doing a short review of the previously embargoed cognitive assessment results.
Slide 2 – Forward Looking Statement:
On page 2, please take note of the forward looking statement.
Slide 3 – Executive Summary
And on page 3, let’s jump right in to some of the more exciting results of the executive summary on slide 3.
So the cognitive assessment by Montreal Cognitive Assessment standard was a prespecified exploratory endpoint of BETonMACE. This was done in patients seventy years and older. BETonMACE inclusion criteria included type II diabetic patients with acute coronary syndrome and low HDL cholesterol. As you’ll see later on in the deck, this is a very high-risk group for dementia. Diabetes patients have an increased risk of developing dementia by 2x. And coronary heart disease and heart failure are associated with a 27% to 60% increased risk of cognitive decline, cognitive impairment, or dementia. There are currently no treatments for addressing vascular cognitive dementia.
Apabetalone treatment illustrated statistically significant improvement versus placebo plus top standard of care in patients with a baseline below 22 on the MoCA score. That MoCA score is 1 to 30.
And we are very very pleased to announce we have a 158% relative improvement in cognitive function in treated patients compared to the top standard of care in the low (below 22) group. [On slide: comparing the mean change from baseline in treated vs untreated groups.].
Significant and trending changes across treatment also showed in biomarkers such as ALP and HDL. [On slide: observed in patients with a baseline MoCA<22.]
So let’s move on to slide 4 and have a look at this...
Slide 4 – BETonMACE Cognition Findings – MoCA
...breakdown of the cognitive findings. And what you’re seeing here on slide 4 is a compilation of the three different groups we used. We used MoCA >26 so 26-30; we used MoCA 25 down to 22; and we used MoCA less than 22. And this is where you find a lot of your dementia patients. And this is where our drug should work; it’s where our drug did work. With 158% relative improvement in cognitive function over top standard of care [plus placebo]. That would be the patients in BETonMACE.
So as you can see, in the higher category, not much change, a little bit dropping in both cases. To be expected. Our drug doesn’t work in healthy patients, it’s not meant to. And in the middle, we see trending towards positive, which is also nice. But in the low group we see very very profound results with a p-value of 0.02.
Let’s move on to slide 5...
Slide 5 – MoCA Domains in Patients with Baseline MoCA <22
To the breakdown of the ten key domains of what a MoCA score is. And they’re listed there I won’t go through them all, but as you can see abstraction and recall are where we really scored quite high. And this is probably due to the vascular nature of the patients. And we had a significant improvement of 0.05 [slide says p<0.05], very nice improvement. And these are the patients with the highest therapeutic need, the below 22.
[On slide: Total MoCA, Visuospatial, Naming, Digits, Letters, Subtraction, Repetition, Fluency, Abstraction, Recall, Orientation].
So let’s move on to slide number 6.
Slide 6 – BETonMACE Cognition Findings – Additional Analysis
And this again breaks it down into the three categories.
Normal: Again, the normal category, greater than 26, if you’re 26 or higher, you’re not deemed to really have dementia or impairment. And we’re pretty much equal in this category as would be expected.
Mild Cognitive Decline: And again in the middle, you see a trending. A little back and forth there.
High Risk: The really nice one is the high risk assessment in MoCA below 22, where we see a profound increase; this is the 158% increase. And this is a great result. Very worthy of expanded clinical study.
And at the conference here this week, you’ll hear or have already heard about Biogen’s drug. It’s a very nice drug, and it (showed) a 23% increase in the subcategory. So we think that’s pretty good. For us, the class of drugs we’re working in, the BET bromodomains, is already known to be very synergistic with other drugs. So whether this is developed on its own or synergistically with others – who knows at this point in time. But it’s very exciting to see this type of result in a category being dementia, that has been a wasteland for a long time.
Maybe this is an accidental breakthrough, maybe it isn’t. But basically these results are very worthy of further study.
Slide 7 – Apabetalone: A New Approach to Neurodegeneration [subtitle slide]
Let’s go on to the new approaches in neurodegeneration. And we’ll start on slide 8; that’s going to touch on...
Slide 8 – BET Inhibition a Potential New Approach to Neurodegeneration
....why we’re so interested in this area. Alzheimer’s disease and vascular cognitive dementia are one very large burden on our health system worldwide. We’re all nervous about this. I read even this week that Bill Gates is nervous about it. That’s the one thing he would not like to have as a health problem, is not having his brain fully functioning.
And there are currently no treatment strategies for addressing vascular cognitive dementia. So a movement like this would be very profound.
The current landscape of Alzheimer’s drugs has not yielded improvements in cognition to date. And the major focus of research has been on beta amyloid and tau burden, that type of approach. Those are single protein approaches versus our multi-pathway approach. And we do believe the multi-pathway approach is the way to go here. And perhaps in the future, synergistically together, that is an alternative approach as well. Time will tell.
And the protein approach has been very expensive with a single target. So multi pathway seems to make sense.
And the commercial opportunity – well, we all know what’s there. It’s huge. So we look forward to developing this.
Now on slide 9...
Slide 9 – Cardiovascular Disease, Diabetes and Dementia
...we talk about vascular disease, diabetes, and dementia. In the little graph there on the left-hand side, we basically see what is the compilation of the BETonMACE trial with an elderly population, the percentage with chronic kidney disease, all of them with type II diabetes, and all of them with cardiovascular disease. This is a high high risk category. And that’s why it’s very important to study them. Because traditionally in a lot of dementia trials, CVD, diabetes, chronic kidney disease - they’re neglected in cognitive function trials because they complicate the trial. So for us, we were doing those patients anyway. We did it the reverse way around and studied cognitive function since we already had the patients. So it provided us with some pretty exciting data on mild cognitive impairment increases in the vascular disease population. The patients in the BETonMACE study are perfect for this type of program. And we aim to reset the clock through this pathway, because a lot of this is deemed to be caused by transcriptional disturbances in epigenetic levels. That’s exactly where Apabetalone works, at the transcriptional level.
[On slide, bar graph from meta-analysis of global studies assessing the prevalence of MCI (mild cognitive impairment) in elderly populations with known risk factors for MCI – including T2DM, CVD, and CKD. Y axis is prevalence of MCI, X axis is categories of risk.
Elderly population: 21%
Chronic kidney disease 29%
Type II Diabetes 35%
Cardiovascular Disease 38%
Inotherwords, these conditions represent increasing risk of cognitive impairment.]
So in slide 10...
Slide 10 – BETonMACE Cognition Subgroup Method Assessment
...we can talk about BETonMACE, the cognition subgroup and the method of assessment. In BETonMACE we used the MoCA study. It’s a very good study for this type of thing. And as a matter of fact its tightest comparison is in the below 20 group, so for us that’s a very nice assessment that we have been able to compile here.
[? Not sure, but I think he means the test is deemed to perform most accurately in that group?]
And the MoCA was performed in all of our patients who were over 70 years old. They would get a MoCA test at baseline and at year one and year two, last trial, that type of thing.
19% of all of our patients in BETonMACE, - being 469, so it’s not a small number, it’s quite a large number – those patients took the MoCA test and that’s where we’re getting these results from. Then we did the subgroup analysis so we would know where this drug is working. Is it working in the sickest patients, the below 22? And the answer was yes. So we’re very pleased to see this going forward.
We didn’t do individual MoCA analysis. We would need a much larger trial for that.
[sic, but I think maybe here he meant they didn’t do individual domain analysis, which it seems they did do some of based on the slide but maybe not in depth.]
So on side 11...
Slide 11 - Apabetalone as a Therapeutic for Cognitive Dementia
...we can talk a little bit about Apabetalone as a therapeutic for cognitive dementia. Apabetalone’s mechanism of action really lends itself nicely to this type of approach – the pathway approach.
We already knew it increased levels of Apo-A-1 and HDL, which are inversely correlated with increased risk of Alzheimer’s disease and positively correlated with cognitive function. So that was one of the reasons we wanted to include MoCA in this particular BETonMACE study. Because we’d had from earlier studies an indication that there really might be something here.
And it reduces the expression of complement and inflammatory mediators, which have key roles in cognitive decline.
And it reduces the expression of alkaline phosphatase and other related biomarkers.
So on slide 12...
Slide 12 – Apabetalone Impacts the Pathways that Drive Disease
...this is not just a wish list of preferred pathways that we would affect. It is our top six regulated by Apabetalone. And this is where we’re getting a real bang for our buck. In coagulation, complement, vascular inflammation, reverse cholesterol transport, acute phase response, and vascular calcification. These are all very important areas of study in dementia. And they’re the top six for Apabetalone. So this is where the strength of our program comes from instead of the single protein approach.
On the summary slide...
Slide 13 – Summary
I’d like to highlight four key and very important aspects of the BETonMACE trial.
The first one on the far left side shows that by replacing stroke with congestive heart failure [in the 3-point MACE primary endpoint]; we would have had a very successful trial with a p value of 0.02. [On slide, 24% hazard reduction, 95% CI 0.06-0.95]. Now, we’re allowed to replace that in future trials. So that’s something we’re working forward to [sic]. And congestive heart failure is a considerably larger market than stroke.
Second from the left, you have the renal subgroup, which was confirmed that the patients with eGFR below 60 at baseline had a 50% hazard reduction. That’s enormous. And again, renal is a category that does not have adequate drugs in it. [On slide: 95% CI 0.26-0.96, p=0.03]
And one of our surprise findings, of the Apabetalone and SGLT2i. Very very nice findings. 66% hazard reduction. And a synergistic finding. Again the synergy of our drug in this category has been very helpful and going forward I think it will continue to be. This SGLT2i is a new type of diabetes drug. And here we are making it work that much better with a p value of 0.05.
Then of course today’s announcement, the cognitive function improvement of 158% in the MoCA below 22 group with a p value of 0.02. Now I mentioned earlier it may be called an accidental breakthrough, but we now have a solid basis to explore cognitive function as a stand-alone or a synergistic drug. And it’s very exciting data. This field in cognitive function does not see results like this. Very very thin results usually occur in trials in this particular category, so clearly I think we’ve done some major breakthrough work here.
Slide 14 – Near Term Commercialization Steps
OK, so on slide 14 we have our near-term commercialization steps. And this is our multi-point approach to progressing the corporate and commercial valuation of the company.
As we’ve mentioned before, we’re applying for breakthrough therapy status with both the FDA and the EMA. The process will take 90 to 120 days.
We’re continuing our SGLT2i partnering discussions. And we’re very excited about the potential there.
The renal partnering discussions are ongoing.
Congestive Heart Failure partnering discussions are ongoing as well, with multiple parties.
Orphan partnering discussions have been in both PAH (pulmonary arterial hypertension) and HIV. We will limit it to those at this time, just to stay focused. And the PAH enrollment has already commenced. The HIV funding is expected to be announced about mid-year.
And then of course after today’s announcement, I will be proceeding further with MoCA partnering discussions. And we’re quite excited about where all this is going, especially in a field like cognitive function, where you really just don’t see results that are 158% improved over treated groups. These results need to be confirmed and validated and moved into the traditional Phase 3 type of approach. But regardless, this is a field that does not see subgroup categories like this and we’re quite excited about moving this forward.
So I’d like to thank you for your participation today, and I left at the back of the deck all of the details on the trial, some of the baseline results, some of the mechanisms of action for your perusal. And feel free to contact us and let us know what questions you may have. Thank you.
This concludes today’s call. You may disconnect your line. Thank you for participating and have a pleasant day.
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