Annual General Meeting, October 3, 2013

From http://services.choruscall.com/dataconf/productusers/resverlogix/mediaframe/6858/indexr.html

Slide 1

Thank you everybody for attending today.Appreciate it.I think we can answer a bunch of questions. What I’m going to do today is stick to Resverlogix.I know many people out there are going to want to ask Zenith questions.So I will stick around after the meeting and gladly answer any of those, but in proper protocol this is the AGM for Resverlogix.And on that note, I will get started.

Slide 2

So today we’re going to go through some of the ASSURE results, some of the review.You’ve seen some of this material before.But we’ll also touch on some new material; some virtual histology that has just come in this week.And again, is very positive news for the RVX-208 drug moving forward.Then we’ll talk just a little bit about expanded indications, and then wrap up with a Q&A and a summary.

Slide 3

So, on September 3rd, exactly one month ago, we went out public with some of the information from the ASSURE trial, that really changed the attitude of whether this drug can or can’t go forward.And the answer was resoundingly yes.It can and will go forward.And the reason being is the drug worked exceptionally well in the right population, the low HDL.And one thing we learned that we did not know before was that the drug works much better with Rosuvastatin or Crestor, and that it’s kind of flat with Atorvastatin or Lipitor.So fortunately for us, this population is the exact population that we set out to prove that it would work in, and that’s low HDL patients on a statin. And the Rosuvastatin is a drug that will go off patent in 2016, so approximately a year or two before we could go on patent. So we’re able to move forward in development with that as Rosuvastatin will be generic.

Now, it works better than Rosuvastatin, in a quarter of the time and a quarter of the dose.So that allowed us to file extra IP.Which is a good thing, because this whole procedure of going through these clinical trials, Phase II, as we’ve talked about many a time is exploratory.And as such we learned exactly what we needed to know here, going forward.There was a point in time in planning the ASSURE trial, that we almost chose to go forward with only one statin, and that statin would have been Lipitor. So I think we got very lucky there, in that we did go with the two statins, and proved out some very positive science.

Slide 4

So I showed this slide during my web cast a month ago, and the yellow areas, especially the five across the top here – (let’s see how that works) - these guys here – those are the p values.And it’s a very busy slide, it’s not really meant to be read from the distance at the back of the room.But the yellows are all statistically significant results in this trial.And as you’ll see, many of them are .0001.Unfortunately the two green ones were the primary endpoint, which had to be announced when it was delivered at the end of June. And those missed by a margin, but none the less, we know why.

Slide 5

And here’s why.The blue bars are the Atorvastatin and RVX-208.As you can see they’re pretty much flat.That’s what Atorva has done in the past.Only on high dose of Atorvastatin do you see a very mild reduction in plaque in an IVUS study.However, when you look at the purple, especially in the low HDL population, where this trial was meant to highlight the results, below 40, you see a 1.43.Well our endpoint was 0.6. So – minus0.6 - so clearly if the trial was just Rosuvastatin the trial would have been a resounding success. However the exploratory data here has confirmed how and why this drug should move forward.

Slide 6

Now there’s lots of results that we put out on September 3rd, way more than we’ve done in the past, because we wanted to show you that this isn’t just a small little sliver of information we’ve found that can help move the drug forward.This is a bucketful of information that moves the drug forward.In this case, you see Rosuvastatin vs. Atorvastatin, and the numbers as you can see all the way through, are quite significantly better in the Rosuvastin, especially in the large HDL down there, 74%.

Slide 7

So we looked at this in terms of breaking it down to see if we could see a dose response, and the answer was yes.The first bar here, the green one, is the announced results, with the .4% plaque regression.The next bar is just the Rosuvastatin patients - so just the rosuvastatin patients - including all of the high HDL patients that probably should not have been in that trial.That one beat primary end point.If you take the 10-20 milligrams, so the higher doses of Rosuvastatin, it’s even better.But if you break it down and you take, just the low HDL patients. These are HDL below 40 and that was what was supposed to be in the trial, you get the 1.43 and on the higher doses of 10 and 20 mg you even get even better.Please note that all of those are statistically significant.

Slide 8

So we do have a very solid drug program moving forward in combination with Rosuvastatin.And the good news there, is although these trials do get delayed and you do have to do extra trials at times, the patent life has now been extended to 2033.And Crestor’s patent life ends in 2016.So this is quite a shift for whoever we go forward working with here.Now there’ve always been questions about the placebo, because of the comment in the news release about the placebo.The placebo effect was strange, but as we break it down on the same chart I just showed you -on the last one, you see the placebo effect wanes off completely.Now placebo doesn’t matter in the last trial, it had nothing to do with the failure or success, because that trial was not against placebo.That trial was against baseline.So the bottom line is if you wanted a placebo based trial, we would have needed 640 patients.And in an IVUS trial where it’s 75,000 a patient, that’s a little unreasonable.

Side 9

So here we are again looking at a comparision to other trials. These trials are from several years ago to quite recent.And you’ve got the REVERSAL, ASTEROID, PERISCOPE, STRADAVARIUS and ILLUSTRATE, all showing their results.This particular one here was not bad, involving Crestor.And then you look at ours.This is all of the Rosuvastatin.This is the Rosuvastatin with low HDL. And this is the Atorvastatin. It doesn’t work.So simple solution. Don’t use Atorvastatin.

Slide 10

Now we looked at the safety in the last trial as well.And again, we see the exact same blip at the six to twelve weeks, or I think this is five to eleven weeks in this case.And it completely goes away, nothing from there on.So we’re very satisfied with the safety results.And the move forward plans are to go forward with the normal drug development and we’re not concerned at all about…..We’ve had all kinds of consultants look at this, including the former head of the FDA liver injury department.These people are not concerned about this drug at all.It’s a much safer profile than many drugs that are on the market right now.

Slide 11

You’ve got drugs that if they show an ALT, the half-life of them, meaning what it takes to come back down to normal, is six to nine months.This is five or six days.So we’re in a very enviable position here with our safety data.Now again on the safety data, when we see these, they’re not causing any damage at all. So on the over three but below five, there’re eight of those.According to study protocol, you just dose right through those.And every one of them adapted on their own.The five to eight category, you suspend, let it go back, re-challenge. Again, they all finished the trial, no problem.On over eight, by FDA standards in a Phase 2 – it’s over 20 in a Phase 3, but in a Phase 2 – by FDA standards you must stop the drug, and don’t put them back on it.So in those, we had an interesting one as well, in that one of the patients was not able to be contacted by the doctor for three days.And by the time the doctor contacted him, and he was still on drug, it had already dropped down, all on its own. So, again the data there was pretty solid in our favor.And I will also note that the problem with ALTs only happens when they are in combination with bilirubin, and we’ve never seen a case of that.And we’ve now had somewhere in the neighborhood of 980 patients treated in our clinical trials.

Slide 12

So we talked a little bit on September 3rd also about the concept of MACE: Major Adverse Cardiac Events.And this is something that really is important going forward.We’re still …As I mentioned in September, it’s going to take a few months to properly design trials, and go-forwards and partnerships around this data.All of that activity is in full swing. We’ve got full support from the Board.Everything is moving forward, but we’re not going to be able to get into a lot of detail on that until we can fully analyze how to do this.

What you really need in a Phase III trial is body counts, because that’s all that’s going to count going forward in Phase III or registration:are you saving lives?And so future trials will involve a placebo, and probably a secondary – you’re going to try to be looking at the MACE events.So that’s death from heart attack, or plain old MI - heart attack without death, a revascularization procedure, or re-hospitalization for cardiac reasons.Often, and we’re not sure if we will or not, often you also include stroke.

Slide 13

So, going forward, we’ll be trying to determine in trials, that you’re seeing event differences between placebo and RVX-208, so meaning that the placebo’s having way more events.And that’s exactly what we saw in the ASSURE trial. We also saw it in the SUSTAIN trial.

Slide 14

So in the ASSURE trial, in the entire trial, we’re seeing half. So that’s a pretty big number in a MACE event.But if you take the Rosuvastatin only patients, and the low HDL , where the trial we know is by far the most successful: look at these differences.I mean that’s pretty significant.And when you look at these numbers, we even get some interesting numbers here –because this one here - one of those four was actually a patient who when tested at the end - blood test – so you do a PK test, and you measure the trough values of how much chemical was in their system. In one of those patients who actually had an MI the last day during the IVUS procedure, he had zero.So it’s a patient who signed up for the trial. He was randomized into the drug dose side, but unfortunately for whatever reason, he decided not to take the drug and report that he had. So not much we can do about that; that happens in clinical trials.But even, you know, we leave him in, to study all the numbers, but even with him, we did quite well.

Side 15

So when you combine the last two trials, that’s 499 patients.And the relative risk reduction is 43%.Now that’s an enormous number.One of the most successful drugs on the market ever, for relative risk reduction, happens to be Lipitor, and they’re at 37%.So if this carried forward into future trials, that is an incredible number that really is where a pharmaceutical company needs to focus, because that’s how they’re going to get reimbursement.Ken Leviota did a study for us about three years ago, with a major group in the United States. It represented most of the top payer groups, so it represented 170,000,000 patients in the United States alone.And in that questionnaire about relative risk reduction, and plaque regression and numbers like this, they were saying that they would make it mandatory for their client base to be on a drug like this at twelve percent, so if these numbers carry through, I think we’re in pretty good shape.

Slide 16

So going forward, we added patents as I mentioned, so we’ve got the one now extended to 2033. I know that’s not much comfort but at least there was some upside about that.Extending the life of the patent is quite important to the end purchaser.

Slide 17

So now let’s get to the virtual histology.This data was not included in September 3rd, because we got the first glimpse of it on September 3rd.So we’ve been analyzing it since and going in, trying to figure out what we’ve got here with this data.Sometimes the newer sciences can be a little confusing.

Slide 18

So what is virtual histology? So in the IVUS as I’ve pointed out in the past, it’s a probe that you’re putting in, and it turns around and has, in this case….Some of the probes we used were Volcano and some were Boston Scientific.So in the Volcano situation, they had the advanced system.So in those probes you have this radio frequency that you get a feedback that can tell you the plaque composition.Or, I usually use this slide with the red, yellow and green.So you want to know, did the vulnerable plaques reduce, and did the more stable plaques increase, meaning the vulnerable ones turned more stable. So the way to think of it is the red (necrotic core) and the light green (fibro-fatty) are the two vulnerable plaques, and the fibrous and the calcium so the dark green and the white are the more stable ones. So this is the information you’re trying to find.And we did this – there were about 85 or 90 patients that were on this particular catheter, so we got a pretty good feedback number.

Slide 19

So our internal way of analyzing this is basically two ways.There is no standard. We’ve run ways that were published. That was good for us. (Not part of talk, but Note on slide 19 says virtual histology analysis was a pre-specified exploratory endpoint in ASSURE)

Slide 20

But the way we look at it is either you take two of the factors, or you take four of the factors, and you put vulnerable over stable and come up with your ratio as to whether it worked.

Slide 21

So basically what we did here is the red is the before, and as you can see, we reduced it.And what we’re doing now, and we just got the extra data this week to even further benefit this data, is we’re breaking it down again - Rosuvastatin and Atorvastatin.And I can already tell you Rosuvastatin was much better than Atorvastatin.So again we get another major data boost that confirms this drug works very well at plaque regression when in combination with Rosuvastatin.And we actually own that patent now, because we filed it.

Slide 22

So when you’re looking at that increase versus decrease in the one system – this is a better, easier way of looking at it I think – but you’re seeing in the 208 vs. placebo, 208’s reducing it, placebo continues to increase in vulnerability.

Slide 23

Again if you use the other system, with the V4 approach, using all four markers, again you get a very nice difference between the two.So good data, very useful in our talks with pharmaceutical companies.

Slide 24

Now expanded indications, we’ll talk about those a little bit and then we’ll go straight to Q&A.

Slide 25

So the Melbourne study is almost fully enrolled.I think we need two or three more patients.So that will be done in the next couple of months.It’s a very slow trial to enroll, even though it’s a small number of patients, because you have to go through a long series of diagnoses to prove that the patient is pre-diabetic.And what they’re trying to do in this particular trial down in Australia, is, it’s an exploratory endpoint,what they’re trying to do is see if raising HDL has an effect on the islet cells,and therefore a huge benefit in diabetic populations.We don’t know.The theory is it should work.We do know that we do raise new HDL, we’ve done it in three or four successive trials. So we will continue to monitor that, and it will be in early 2014 that we should receive some data for publishing on that particular study.

Slide 26

Now the Alzheimers trial we’ve talked quite a bit about.We’ve had a lot of discussions with the National Institute of Health in the United States, in particular the NIA, National Institute of Aging.Alzheimer’s has become a very very popular item down in the United States, because even in the Obama budget last year, he added an extra $100,000,000 for Alzheimer’s research, and he has challenged the NIA to come up with a meaningful drug in Alzheimer’s. I say meaningful, stressing it, because out of the last one hundred and five trials, they’ve had three successes, and those were symptomatic drugs.So dealing with the symptoms of Alzheimer’s not the cure.So they’re really throwing a lot of money at this right now. And in discussions with pharmaceutical companies about RVX-208, I must admit in the last month, the interest level for Alzheimer’s has been as high as the interest level for cardiovascular. So our approach is based on - Alzheimer’s correlation to Apoa1 is kind of two fold. Apoa1 is responsible for the integrity and the health of the blood brain barrier, so increasing Apoa1 is a very positive move for the blood brain barrier.So in Alzheimer’s you get seepage from the blood brain barrier.That’s why sports injuries like boxing and football are similar at times with the brain injuries because it’s the seepage.So curing, by making the blood brain barrier healthy is a real plus.Now most, a lot, probably 60% of those failed trials were dealing with something called beta amyloid 40.Now in an Alzheimer’s patient, you see a brain like this that’s all shriveled up and gooey.And what’s on it is beta amyloid 40. It’s a very sticky substance.Its closest known chemical entity is the sticky side of a barnacle. So of course it made sense to go after that as a target, assuming that that was the culprit. Now other studies have recently shown, that when Beta Amyloid 40, this sticky substance, is in combination with Apoa-1, it’s non-toxic. So as you get older, and your APOA1 drops off, the Increase in Alzheimer’s is an almost identical curve in the other direction.So, we have two really good reasons to believe that this should work. And we continue to work with NIA and NIH on funding this trial.There is a procedure that we have started up.It’s not a fast procedure, but hopefully we will be able to move forward with that.

Slide 27

And on that program we have put together an extremely strong board of advisors for a clinical trial and how to design it, and what we’re looking for.If you look up any one of those individuals, you will find that they’re the who’s who of Alzheimers research.In fact the first one there, Bengt Winbladin the annual Alzheimer’s global meeting, the top research prize is actually named after him.

Slide 28

So, on that note I just want to summarize before our Q&A that RVX has proven that we regress plaque in the right population, in the low HDL population, which is where we were trying to prove it, and on Rosuvastatin.Combined with Rosuva, we saw positive impacts on almost all of our bio-markers, except our primary endpoint. (I think maybe he mis-spoke here? In combo with rosuva only, the primary endpoint would have been good) The virtual histology again backs up our data, and once again shows it works best with Rosuvastatin.So we’re continuing the programs in cardiac, Alzheimer’s and Diabetes.And as we get into the Q&A here, I’ll answer as much as I can, but remember we’ve only had this data for four weeks, and trying to go out to pharmas and get an idea of how fast you can even set up a meeting, let alone get a potential partnership put together, it takes a while, but we are moving along, and we’re looking forward to getting this drug back into the recognition that it deserves.

All right, on that note, I’m going to wrap it up, but I will stick around to discuss with you about Zenith if you’re interested, and in the future we do have to keep the two separate.So bear with us on that.As, since we split the company on June 3rd, there’ve been over eighty million shares traded in Resverlogix, so they’re not really the same stock baseanymore either.Alright, thanks for attending today, I really appreciate it.