Resverlogix Webcast  - Detailed Preliminary Results of BETonMACE - 11/18/2019

 

https://78449.choruscall.com/dataconf/productusers/resverlogix/mediaframe/33463/indexl.html

 

1.       Cover Slide

Thank you for standing by. This is the conference operator. Welcome to the Resverlogix conference call and webcast to present detailed preliminary results on BETonMACE. 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 star and zero (* and 0). I would now like to turn the conference over to Mr. Donald McCaffrey, President and Chief Executive Officer of Resverlogix Corp. Please go ahead.

 

Good morning ladies and gentlemen. This is Don McCaffrey. I’m the President and CEO of Resverlogix, and it’s a great pleasure to be here today to be giving some additional updates on our drug development program. I will start today by reviewing the executive summary of what will be covered. But first I’d like to comment on our late-breaker presentation that happened at the American Heart Association on Saturday. It went exceptionally well, with over 3,000 people in attendance leaving the session believing that with a little more work we have a very good and safe drug. Today I will touch on the strictly academic information presented at the American Heart Association, but I’m also going to discuss the broader findings that will further confirm Apabetalone’s approach as a registerable drug.

 

2.       Forward Looking Statement

 

3.       Executive Summary (1)

OK, now in the Executive Summary Slide on page 3, we have very encouraging disease efficacy results. The primary endpoint was a near-miss, as we already know since September 30th, and the exact data is listed here. So your hazard ratios etc., p values. The line below that actually determines a secondary approach to that. The primary, and then the one excluding undetermined causes of death. [ On slide: 18% hazard reduction, 95% confidence Interval 0.65-1.04, p=0.11; and 21% hazard reduction, 95% confidence interval 0.62 – 1.01, p=0.06 excluding undetermined cause of death.]

 

I will discuss that shortly and then we’ll even show you a third approach to this later on, on slide 13, which I find highly intriguing.

 

Trending MACE improvements on multiple endpoints as shown in a Forest plot will also be shown.

And a very solid hit on hospitalization for congestive heart failure. Very very good data.

 

The most pronounced primary endpoint hit will be shown as well and these are dealing with renal function and LDL below median. [On slide: impaired renal function: 50% hazard reduction, 95% CI 0.26-0.96, p=0.03; and baseline LDL below median 40% hazard reduction, 95% CI 0.42-0.86]

 

Critically important findings have occurred. Patents have been filed. New ones are in progress of being filed. And these patents have enormous commercial value. And they will play out in the short term. Potential synergy with new generation of diabetes drugs was also discovered. The primary endpoint involving SGLT2 drugs was highly encouraging and involved some of our early new patents filed.

[On slide All SGL2i’s: 60% hazard reduction, 95% CI 0.16-1.00, p=0.05, non QC’d and

Empagliflozen 66% hazard reduction, 95% CI 0.0.12 – 1.01, p=0.05, non-QC’d]

 

4.       Executive Summary (2)

On slide 4, continuing the executive summary, we’ll also have a short discussion on the cognitive impairment data and what’s going on there and when it will be delivered. We have significantly enhanced intellectual property as I’ve already been indicating. And it will continue. It will continue for years because the amount of data here is enormous. We’re still filing patents off of the information from our last trial.

So further development of Apabetalone is well under way, as you’ll learn more about today; and we’re considering multiple paths going forward, dealing with the FDA and the EMA on breakthrough therapy statuses and new trial designs that will further strengthen the attributes of Apabetalone.

And in the appendix, there’s a lot of slides on here, so don’t worry, I’m not going through eighty some slides. We will leave the last half of the deck for you to review so that you have all the information. [Slide deck includes 6 slides.] You have the BETonMACE review, the study design, the baseline characteristics, the safety evaluation, and a little update on mechanism of action. You’ll see that it’s a great data set. It was a very well-managed trial. The patients are on top standard of care, all of them. So the results you’re seeing are that much better than anything else on the market. And that means we’re not competing with somebody. Maybe in some cases it’s synergistic, which we really like. But we’re making the patients better. This is really important. Because these patients, they’re me, they’re you, they’re your grandparents, they’re your parents, they’re your brothers and sisters. This category needs work, and I think we’re there.

We had great safety results as you’ll see; and we’ve had very positive comments from the regulators and our data safety management board on the safety profile. So we’re very very pleased with that.

 

5.       Cardiovascular Disease Efficacy Results (Section Slide)

But moving on to the cardiovascular disease results, the efficacy results...

 

6.       Primary Endpoint (Subsection Slide)

We’ll jump right to slide 7.

 

7.       Primary Outcome Measure and Components

This is kind of the primary official ... what was officially presented at the AHA on Saturday. And they have their strict academic standards. You set your marks early and you can’t change them. You can learn from them, and we certainly have. And we’re going forward with it.

 

So this particular slide is showing a composite of the three endpoints that were approved by the FDA and the EMA. Two out of three worked well and the stroke component let us down. There were 17 in each category [treatment and standard of care+placebo], so it was pretty much dead flat.

Regardless, future planning can exclude stroke, and it can include some of our most successful categories that we learned from this trial. And that’s precisely what you’ll see we will be doing.

 

 

 

On slide:

*Nominal p value

 

8.       Primary Endpoint: Narrowly Defined MACE

So on slide 8, this is just a different way of looking at the primary outcome measures. And to me it’s easier to look at. As you’ll see the early separation of curves – happens immediately. And this is very good news for us in future trials, because they can be shorter, faster, cheaper. And you’ll also see they’re sustained throughout the trial, which is very good news for us. We’re quite pleased with the data on these particular slides. 

 

9.       Primary Endpoint Excluding Undetermined Deaths

Now on slide 9, this is a different approach. This is looking at excluding undetermined cause of death. So in a trial, you don’t always get an exact cause of death when you send the stats over to the data safety monitoring board and the review committees. In this case, there were about twenty that were undetermined. Sometimes you decide to add them to the number, sometimes you decide not to add them to the number. It was our choice to add them to the number. And if we hadn’t, we still would have missed. The number would have been agonizingly closer as you can see, but it’s still a miss. But it’s showing that those that were adjudicated as true cardiovascular death, MI, or stroke were even closer to that line. So this is very encouraging news for us overall, and helps us plan going forward.

 

10.   Secondary and Other Prespecified Endpoints (Subsection Slide)

Now let’s move forward to the information on secondary and other pre-specified endpoints.

 

11.   Forest Plot Primer – Presented at AGM

Particularly slide 11. This is the famous Forest plot. We talked about this at the AGM. And so here we go. What did the overall data say? Well, just to give a little review of this, the Forest plot is a way of educated scientists, researchers, clinicians quickly looking at a large set of data and determining if it’s worth following up on, reading more on, and such. On the left-hand side of the line, you have solid good data. On the right hand side, placebo was probably better. And in this case, please always remember that “placebo” is stop standard of care. [BETonMACE compared patients on standard-of-care plus Apabetalone to patients on standard-of-care plus placebo]. So placebo would be better on the right hand side, and our data is better on the left hand side. So let’s go to slide 12.

 

12.   Cardiovascular Endpoints

Well the answer is hell yes. The data is much better. As you can see, 11 of the 12 hazard ratios are improved in this study. These are pre-specified endpoints. The only one that’s neutral is our friend  stroke. So this tells people, this told us, this is extremely exciting data. And a drug worthy of following up, partnering and moving forward. Note the two highlighted sections. They were both significant hits. And they’re also in the same indication, congestive heart failure. We will refer to that as CHF mostly here. And notably, this market, CHF, is twice the size of the stroke market. So that’s a nice finding to have, and we already know it works based on this data.

 

13.   Alternative Primary Outcome Measure and Components

So let’s go to slide thirteen. This is where it gets really exciting. Here we utilized the pre-specified endpoint data, and we looked at three-point MACE involving death, non-fatal MI, or hospitalization for CHF instead of stroke. It was phenomenal. We would have had a very different trial result. And this confirms our program. We already know it works, and it works very well. Nothing stops us from running future trials or work programs on three-point MACE with death, MI and CHF. So obviously that’s a fast quicker [sic] way for us to move forward. And that’s how we will be moving forward.

 

On slide:

 

 

 

14.   Alternative Primary Outcome Measure – Survival Curve

On slide 14, let’s look at this one. This is again the same data as the last slide but presented in a chart format. And again, it works. It works very well from start to finish. So we can run faster shorter trials. We know the populations we want in the trial. And away we go.

 

15.   Hospitalization for Congestive Heart Failure (CHF) (Subsection Slide)

OK, let’s talk a little bit more about CHF, congestive heart failure. And we’ll start on slide 16.

 

16.   Key Secondary Endpoint – First Hospitalization for CHF

This again is some of the data from our Forest plot translated into a chart format so you can really see what’s going on. It even prevents hospitalization for CHF versus the top standard-of-care drugs. And one of those is a drug from Novartis called Entresto (sacubatril/valsartan). It’s a very good drug. Currently leading in the CHF field. However, their patent expires in about three years. And we have twice the effect that they have. [I think he means here that Entresto + Apabetalone  is twice as effective as Entresto + placebo, but not certain.] We’ll also be looking at synergy between their drug and ours in the coming months. So very exciting opportunities for us here in CHF. And the CHF market happens to be twice the size of the stroke market.

On slide: Graph of effect, with info HR 0.59, 95% CI 0.38-0.94, p = 0.03, 41% hazard reduction.

 

17.   Exploratory Endpoint – First Hospitalizations for CHF or CV Death

OK, on slide 17, again exploratory for CHF in first hospitalization, we have great data. This is exciting people in our discussions and I can see why. Because going forward, a drug that is this safe, and has this kind of impact over standard of care, and has now patent lives out very far, that’s just going to be quite helpful.

[On slide: Graph of effect with info HR 0.73, 95% CI 0.53 – 0.99, p=0.04, 27% hazard reduction]

 

18.   Prespecified Subgroups – (Section Slide)

Now let’s go into some of the prespecified subgroups.

 

19.   Endpoint Significance Reached in Prespecified Subgroups

We’ll start on slide 19, and go through the endpoint significance reached in some of these prespecified endpoints. So we’re doing another Forest plot here. And you’re seeing the breakdown of all kinds of categories, whether it’s gender or drugs that they were on or statins that they were on. But we had two that really stood out, two notables. And they’re involving renal, and surprisingly LDL. That’s not one that we had anticipated, so we’re digging into that a little bit more. Let’s start reviewing these by looking at first the renal, which was very solid data.

 

20.   Apabetalone Overperforms in Patients with Renal Impairment (Baseline eGFR Below 60 mL/min) (Subsection Slide)

On slide 21...

 

21.   Apabetalone Improved CVD Outcomes in Impaired Renal Subgroup – Forest Plot

You’ll see a specific Forest plot for the renal. Now the way this is broken down is each category listed on the left side, the endpoint, has two parts to it. One is their glomerular filtration rate below 60, meaning you have some level of chronic kidney disease, and that above 60 meaning you don’t. So our drug was designed to work best in patients that are sick. The reason being is when you’re below 60, you start to have problems. You start to have coagulation issues, you start to have inflammation issues, etcetera. We’ve detailed this in great detail over the years, especially with our New Zealand trial. And you start to attract these bromodomain 4s and those are the culprits. What we do, is we inhibit the bromodomain 4s. So in the healthy patient, they’re not there. So the drug has virtually no impact in the healthy patient. The next several slides will highlight that quite clearly. And in a sick patient, it has a profound impact. And there aren’t reliable drugs out there for these patients. CKD patients unfortunately are managed, from stage 1, 2, 3, 4, through dialysis, through death. And we’re hoping to reverse that trend. We think that there is great potential here. And you’ll see it going forward. Now on slide 22...

 

22.   Apabetalone Improved CVD Outcomes in Impaired Renal Subgroup – Numbers

We’re looking at the breakdown of that information. The top box is showing you the below 60 eGFR. The sick patients. And the bottom box is the healthier patients. This clearly indicates with 7 out of 12 [endpoints] in the top category that are statistically significant, we’re having a very large impact on the health of these patients. Whereas below, on the healthy patients, we’re zero for twelve [in significance]. We have no impact, the drug was not designed to work here. Which actually helps us with our safety profile as well. Now these seven I’m going to highlight over the next few slides. I won’t spend too much time on them, but it is exciting to see. So on slide 23...

 

23.   Renal Subgroup – Narrowly Defined MACE – CV Death, non-fatal MI, Stroke

Your renal subgroup, this is the narrowly defined MACE [CV death, non-fatal MI, stroke]. Below 60, what a difference. That is just not available in today’s drug market. And above 60, they’re the same. So an incredible difference. And the statistical significance is there on all of these.

[On slide:  hazard ratio 0.50, CI 0.26 – 0.96, p=0.03, 50% hazard reduction.]

 

24.   Renal Subgroup – Narrowly Defined MACE – CV Death, non-fatal MI, Stroke excluding undetermined cause of death

Let’s go to slide 24. Same thing, a narrowly defined renal subgroup [in this slide excluding undetermined cause of death]. We have huge differences between the two categories. And again, Apabetalone treated versus [on top of] top standard of care in the world today. That’s an incredible chart difference on 24.

 

[On slide, hazard ratio 0.47, 95% CI 0.26-0.86, p=0.01, 53% hazard reduction.]

 

25.   Renal Subgroup – Broadly Defined MACE

Now if we go to slide 25, renal subgroup of broadly defined MACE, this is more like your five-point MACE {CV death, non-fatal MI, stroke, hospitalizations for CVD events). Same thing. By five-point MACE, I mean, it’s not as strict but it comes down to some of the extra points, like hospitalization, revascularization, stuff like that. Those are important and they are expensive medical procedures that cost health payer groups a lot of money. So when you can reduce numbers like we have on this particular chart, this is impressive. This is very impressive. Yet again, over on the right hand side for those above 60, flat as a pancake. So we’re pretty convinced of what we have here, and so are the people who have reviewed this already and are in discussions with us. So we’re excited about where this is going.

 

[On slide: hazard ratio 0.53, 95% CI 0.30 – 0.94, p=0.03, 47% hazard reduction.]

 

26.   Renal Subgroup – CV Death or Non-Fatal MI

Now on slide 26, our renal subgroup, this is for CV death or non-fatal MI, and again, statistically significant in the right population, way better than standard of care, two-to one, and in placebo [sic], or top standard of care, flat as a pancake again. [ I think he misspoke here, I think he meant to refer to those with eGFR³60. These actually almost all seem to have a non-significant and small beneficial effect, vs. actually being completely fact, but it may be of no clinical significance.]

 

[On slide: hazard ratio 0.53, 95% CI 0.29 – 0.98, p=0.04, hazard reduction 47%.]

 

27.   Renal Subgroup – Hospitalization for CHF

So slide 27, once again, hospitalization for CHF in renal patients, this is one of our biggest performers. So this is big news for us to be able to show that chart and have the other results in CHF and know how to swiftly progress the development of Apabetalone into a three-point MACE including CHF.

 

[On slide: hazard ratio 0.36, 95% CI 0.14 – 0.93, p=0.04, hazard reduction 64%.]

 

28.   Renal Subgroup – Hospitalization for CVD Events

And for slide 28, almost done. For slide 28, in the renal group, for hospitalization due to CVD event, even more. It’s enormous. This one is quite impressive. And again, most CKD patients end up dying from cardiovascular disease. And when you can reduce events like this, that’s a big step forward in drug treatment. And people looking at this at AHA and in discussions before and since AHA are in full agreement that this drug has some exciting potential here.

 

[On slide: hazard ratio 0.28, 95% CI 0.11 – 0.73, p=0.01, 72% hazard reduction.]

 

29.   Renal Subgroup – Hospitalization for CHF or CV Death

On slide 29, this is the last of the renal slides. This is hospitalization for CHF and/or CV death. So again, statistically significant. We were in seven of the twelve categories, and not just by a little bit. But in huge numbers. So we’re quite pleased. And the comparison in each case to the above 60 baseline was very interesting. I mean consistent all the way through, so not fluke data; it’s pre-planned, pre-specified, and confirmed.

 

[On slide: hazard ratio 0.5, 95% CI 0.25 – 0.99, p=0.05, 50% hazard reduction.]

 

30.   Apabetalone Significantly Reduced MACE Risk in Low LDL Subgroup (Baseline LDL Below Median) (Subsection Slide)

OK, now we’ll move on to the MACE risk in low LDL patients. And this is a much shorter section.

 

31.   Apabetalone Reduced MACE in Low LDL Subgroup – Forest Plot

So on slide 31, we have our Forest plot showing Apabetalone reduced MACE risk in low LDL subgroups. And as you can see, the low LDL outperforms the high LDL by quite a bit. This was a surprise finding for us. We’re not quite sure what it means yet. But it certainly would be a positive.

Let’s move on to slide 32 however.

[Seven endpoints shown. LDL<Median outperforms LDL³Median for all endpoints.]

 

32.   Apabetalone Reduced MACE in Low LDL Subgroup – Numbers

As you can see here, we had nine of the twelve [endpoint] categories listed here were statistically significant in the low LDL subgroup. So this is worth following up on to determine what we can do with it, how we can benefit off this. I won’t go through those nine now, as we want to study them more first. But we will keep an eye on this category moving forward.

 

33.   LDL Subgroup – Narrowly Defined MACE

The only one I will touch on is the narrowly defined MACE on slide 33. And as you can see, highly statistically significant, very good separation of curves, and yet when you go into the above median LDL they track almost identically. So there is something here. We’ll figure it out.

 

[On slide hazard ratio 0.60, 95% CI 0.42-0.88, p=0.02, 40% hazard reduction.]

 

34.   Surprise Finding! Potential Synergy with New Generation of Diabetes Drugs (Section Slide)

Now, let’s move into my favorite category, some of the surprise findings. The potential synergy with the new generation of diabetes drugs.

 

35.   Baseline Characteristics: Cardiovascular and Diabetes Medications

We’ll start on slide 35. This is the baseline characteristics of the cardiovascular and diabetic medications that were in the trial. As you can see, there were a lot of drugs being used. There were a lot more than this. But when we planned our trial, we planned it with drugs of the time, which was 2015. And the two circled on the bottom there, highlighted on the bottom, SGLT2 inhibitors and GLP1 receptor agents, they were virtually non-existent in 2015. And yet by the end of our trial, 16% of the population was on these drugs. And that had some impact on our trial, maybe a little bit negative on our endpoint, but also very very positive up along the way. And what I mean by that is, when we first planned our trial, our placebo or top-standard-of-care group, was anticipated, like many other trials, to have an average event rate per year of 7.5%. Well, it actually had 5.8%, meaning they were healthier, better treated. These two drugs were the two new ones, so that probably had something to do with it. Fortunately for us, we outdid those two drugs and synergistically, I think we work very well together, so this isn’t a competition story, this is a synergy story. And those I like much better. So let’s look on slide 36.

 

36.   Comparison to Other Major Therapeutic Classes

This is a comparison of other major therapeutic classes. And keep in mind, these aren’t competitors of ours. Some of them are diabetes drugs, some of them are LDL modulating drugs. We have our own unique category, but we do work together. And these are trials or groups that have done MACE studies. And as you see the DDP-4 had no effect; the insulin studies, no effect. SGLT2 on their own, not bad, about 14%. PCSK9s, expensive but only 15%. And GLP-1s, that’s still in discussion as to where those numbers will fall [slide says 12 – 26%]. But there we are, at this particular trial, at 18% already. And of course I’m going to highlight the Apabetalone and SGT2i numbers. Staggering. This IP has already been filed. And a 60% effect on MACE in conjunction with those drugs is a very surprise finding. And we are very pleased to now own the intellectual property on it moving forward.

 

37.   Apabetalone Reduces MACE Beyond Benefit of New Diabetes Drugs

On slide 37, we’ll look at the effects of Apabetalone vs. some of these new diabetic drugs. As you’ll see the patients that are taking a combination of Apabetalone and SGLT2 inhibitors are the low columns. The high columns are the placebos without Apabetalone. So clearly this is a huge difference with relative risk reduction numbers in the 60 range, so this is pretty impressive data and we expect to be able to do something commercial-wise with this in short order.

 

38.   Apabetalone and Empaglifozin (Jardiance)

OK, so let’s move to slide 38. This is looking at Apabetalone and one of the leaders in the SGLT2 inhibitor category, a drug called Jardiance.  This is a drug co-owned by both Eli Lilly and Boehringer Ingelheim. They’ve done quite well with this drug. The market share for last year was showing them somewhere around 43% of market share. However when we broke our data down, they had about 80% of the market share. So I don’t know if the improvement has been that much or it’s just the markets we used. But regardless, when we look at the effect versus Jardiance and Jardiance and Apabetalone together, very very solid data in our favor. So this is also quite helpful and material for filing a patent.

 

39.   Market Growth of SGLT2 Inhibitors

Alright let’s look at slide 39 now. The market growth of the SGLT2 inhibitors. It has been quite a fast growing category. This year it’s expected to be 6.5  billion dollars. And raising at 14 plus percent per year. I personally think it will go higher. They’re effective drugs. But as I showed you, we’re twice as effective in combination with them. So this isn’t a competition story, it’s a synergy story, which I like even more. On the right hand side, the Jardiance market growth. As you can see in 2015 and when we planned and started our trial, this was an afterthought. I mean in 2015 they didn’t barely exist [sic], and now they’re huge. So they had an impact on our healthy patient’s event rate, but the surprise finding for us and our ability to file this clearly non-obvious market information is going to lead to some huge commercial valuation for the company.

 

40.   New Findings Presented at CTAD Symposium – December 5th 2019

Now, new findings. On [slide] 40, we’re also going to talk just a bit about the CTAD conference coming up. This is Clinical Trials for Alzheimer ’s disease, is what CTAD stands for. And we haven’t talked and we won’t talk much about our cognitive function data until December 5th when this is presented, for the same reason we haven’t been able to talk until this weekend about our true exciting data, because of embargoes for academic purposes. You will be very pleased to know these are the last two. We do not have future embargoes coming up. So in the CTAD conference in San Diego we will be participating in this session, and showing a lot of the data involved in our cognitive function. And I think you’ll find it quite exciting. Again, after this conference, we will do a webcast and update the market as well.

 

41.   Summary

Alright, let’s move on to the summary slide on page 41. This basically confirms that we did miss the primary endpoint barely. But we have very strong trending data and it’s crystal clear how we move this drug forward for approval. And we can plan around things like that 5.8% event rate instead of the 7.5. We know it’s there now. And we also know we have a huge benefit from it being the SGLT2 category. So just to remember in following up on this, the narrow MACE with CHF would have been highly statistically significant. And we can move forward, and will move forward  with plans to show just that. The renal subgroup below 60 GFR baseline had phenomenal data, again highly statistically significant, and lots of categories to encourage co-development with that one as well. And Apabetalone with SGLT2 inhibitors, very exciting data. Synergistic data. And obviously we will be in discussions moving that one forward as well.  

 

42.   Near Term Commercialization Steps

OK, let’s move to the final main slide here now, the near term commercialization steps. Now we kind of have a five-point approach here that we’re following and this is what we’ll be doing over the next few months. One of the key areas is the breakthrough therapy status filings, and we’ll be doing that both at the FDA and EMA. We believe we have what it takes to get that done in the next 90 to 120 days. And we’ll be moving forward in that type of direction regardless. So, SGLT2i partnering discussions, one is already initiated and key patents have already been filed. That is an exciting category. Renal partnering and discussions are moving forward. Congestive heart failure partnering discussions, already initiated. And we will continue with our orphan partnering discussions but we’ve narrowed it down to two only at this time just to stay focused. And they will be PAH and HIV only at this time. The PAH enrollment has already commenced. And the HIV funding has been derived and yet to be named yet [sic] from a US organization.  So going forward, these five areas are going to add a lot of commercial value in the very short term.

 

43.   Cover Slide – Detailed Preliminary Results of BETonMACE

Now for the rest of the deck, as I mentioned right at the beginning, we have a lot of data for you here in these categories. And we want to make sure that you’ve had access to it and it covers the BETonMACE review, study design, baseline characteristics, safety evaluation, and some mechanistic data. So enjoy going through that, and we look forward to moving this program forward quite fast. Thank you very much.

 

This concludes today’s conference call. You may disconnect your lines. Thank you for participating, and have a pleasant day.