My version has slides above the corresponding text, but the image import function was too cumbersome for me to do that here.  Also, in general, people's live speaking grammar is not textbook. I debated about whether to make corrections, but mainly did not. 

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So today we’re going to review a lot of the details of what happened this year and what’s projected to happen next year.  And we look forward to a Q&A session at the end of the presentation. 

So, the corporate overview.  As you know, Apabetalone is our lead drug and it is first in class.

We run our offices in Calgary and San Francisco.  First in class molecule BET bromodomain inhibitor, which is getting a lot of press these days.  We’ll talk about that going forward as well.  And Resverlogix has initiated clinical trial work for Apabetalone in three indications: cardiovascular disease, chronic kidney disease, and Fabry disease.

This is the capitalization and financial profile.  As you know the shareholder list changed quite a bit in the last few months.  We believe for the positive.  And the market slides and capitalization I did yesterday, so they’re a little on the high side for today’s stock.  Sorry about that.  But yesterday morning the market cap went up to $425 million, which is something we’ve waited a long while for.  I still think that’s exceptionally low and we should see it climbing back there and past there. Outstanding shares are $175 million.  The annual burn rate is just over $40 million dollars.  And as you know we closed an $87 million dollar financing in December.  And we’d like to thank Hepalink for that, and Sean Lu is our Hepalink Board Member, so thank you Sean.

Now going forward – as I said, these are yesterday’s slides.  Things change rather quickly in this business.  But yesterday morning when this slide was prepared, we’d jumped quite a bit, which was a nice increase over the stock price the previous year (40%).  And the market cap again, a very large increase (134%) over last year’s.  And the AGM last year was almost the exact same time; it was December 15th, 2016.

So major accomplishments in the year.  We’ve had a very eventful year with FDA approvals in both chronic kidney disease and our planned go-forward trial, and the ability now to have U.S. patients in the BETonMACE trial.  That’s a work in progress; we should have our first patients in the trial early in next year.  And we had successful data from a kidney trial we ran in New Zealand.  I’ll show some of that at the end of the presentation when we’re talking about the chronic the kidney disease program.  Very successful data, very exciting first-time-ever data in epigenetics.  Above and beyond the $87 million, we financed over a $100 million this year.  So it was a good time to get the money, as you all know, we had a debt to repay ($68.8 million).  So it was nice to get that monkey off the back.

Now publications.  So I had listed yesterday morning four.  That now is five as of today, as there’s a brand new one out today from Kidney International, which is the most cited journal in the nephrology field.  So brand new paper out, not the one we news-released this morning; that was not our paper.  The one today is.  So that would make five publications in 2017, and we already have five in progress right now for 2018.  So a lot of activity on that front, and that gains us huge credibility.  That really helps.  Five years ago when we’d get talking to pharma, they’d get all excited and they’d want to see publications to back this up.  Well, we’re the leaders in the field.  So it’s a beautiful place to be ten years ahead of everybody else.  And it’s a horrible place to be, because you’re ahead of the curve on the knowledge and the publications.  So we’re very actively working with others to speed that process up and it’s been very helpful.

 Alright and of course, the other one I have up here, just some of the major ones – that $68.8 million dollar debt repayment was quite nice.  You did see a lot of stock activity.  The reason you saw it on the day it was repaid as opposed to the day we received the $87 million dollars is quite simple.  Many funds out there in Toronto New York and other places have corporate mandates.  And one of them is not to be able to invest in a company with long term debt.  So as soon as the debt [payment] was announced, you saw millions of shares move in.  We’ll try to continue that process.  At 6:00 tonight I’m actually on an airplane on another road trip, going out east to keep the activity going.  We have a lot to talk about, and these guys have some catching up to do on the learning.  We believe we can keep the volumes up.  Not as high as the last week, that was pretty impressive.  But I believe we can get our averages up.

 So the communications have been numerous in this particular 12-month period. Other than your normal type of accounting type of news releases, (and sorry to belittle accounting for you accountants), we had about 14 major announcements this year.  We’ll try to keep it up for next year as well, and just keep talking.

 The other corporate profile item is we do have a major partnership in place already with our China licensing deal with ShenZhen Hepalink.  And as you can tell from their support of the company, great company to work with.  We look forward to our licensing deal continuing on in China.

Now let’s talk a little bit about Apabetalone and the mechanism by which it works, which is BET inhibition.  Now normal drugs work on protein modulation.  Either trying to raise or lower a certain protein or correct a certain protein.  We work way upstream of that, before the protein is made, we’re changing what the DNA is saying to make.  These proteins that require medication, they’re clearly – there’s too much of it or too little of it, or they’re not functioning properly.  So we do believe quite intently  that fixing it at the transcription level , when it’s actually made, what’s being directed to be made, is a very smart approach.  And upstream of us even is a technology called CRISPR.  And as you probably have heard about CRISPR.  It’s interesting future technology.  And I am really glad I’m not the CEO of a CRISPR company.  Because if they think the STEM cell guys had a rough ride, they’re in for a rough ride. It’s good technology; it should be followed up on.  But when you start talking about changing human DNA, that riles a few feathers, left right and center.  So I’m glad we’re just below that.  As effective or more effective in my opinion.  But I think it’s a great place to be working.

 So let’s talk about the differentiation.  There are a few other BET inhibitor companies out there.  Every single one of them is working in oncology only.  And that’s because they don’t know anywhere near as much about BET inhibition as we do.  Some of the ways we’ve learned about that is we have the only blood bank in the world of BET treated patients.  And we were able to reverse engineer in our own labs, and contract others to work with us.  So that was quite helpful.  We had the only blood bank, so it was the only tool.  And you need that tool.  Harvard, Oxford.  They don’t know as much as we know, because they didn’t have the tools to work with.  So we are publishing some of that and sharing it now and we’re having a lot of fun teaching Harvard how it’s done.  And of course we have a very good safety profile, because we’re a selective BET inhibitor.  Where all of the oncology ones they hit BRD-2, 3, 4, T ...and the BD-1s and the BD-2 inhibitors.  We’re selective primarily for BRD4-BD2.  And we have follow-on compounds that can be selective for just about any one of those.  Whether it’s a BD-1, BD-2, or BRD- 4, 3, 2.  So we’re pretty advanced in this.  And it’s helping us in our discussions.  Both in regional licensing deals and pharma discussions.  Because clearly we know what we’re talking about, and there’s no hidden little ghosts out there in a black box.  We know how the mechanism works.

So one thing we’ve learned a lot in the past is the pathways involved here.  So when we reverse-engineered all that technology we found six key pathways.  Vascular inflammation, I think that’s self-explanatory.  Reverse cholesterol transport.  Ring a bell?  That’s where we started.  And that’s how come we were able to discover this.  Metabolism.  Vascular calcification.  Coagulation.  And one called Complement pathway, a lot of people don’t know about.  But it’s the body’s system for handling invading pathogens.  And that one’s quite high on our list of programs.  We’re pretty excited to see that one.  We’ve done a lot of work to try to figure out what is the best clinical approach to that.  It will take a little bit longer but not much longer before we can delve a little bit more into some complement-related activity.

So now let’s talk about the clinical trials.  I think that this is what excites most people right now, because quite frankly half way or three quarters of the way through a Phase III trial – it’s getting pretty exciting.  This data here is finally published.  It only took Steve Nicholls about four years, but we appreciate his work.  And as you can see the numbers are a little bit different than what I’ve used in the past, as they have used a different analysis system.  None the less, highly statistically significant, and very much in our favor.  Showing exactly what we wanted to show - that this drug has a very profound impact on MACE reduction, particularly in diabetic patients and those with an inflamed vasculature, which would be  those with high inflammation markers such as CRP.

So we’ve done a ton of trials in the past.  There are three ongoing.  Two of them are not active for recruitment right now, but they will be shortly.  And BETonMACE, we’ll touch on it in a separate segment.

I guess this is the segment.  So BETonMACE was planned to have 2,400 subjects.  And all of these patients are on either atorvastatin or rosuvastatin.  And I just got a review with the directors this morning as to where those numbers stand.  And it’s pretty much almost 50-50.  It’s one or two percent on either side whether they’re Atorvastatin or rosuvastatin.  So this is a great great addition.  Now as you recall back, we were pretty proud of the rosuvastatin data we had, and we were just going to run it with just rosuvastatin.  We got the nod, almost Okayed.  Probably would have gotten it approved in Europe.  But in our early discussions with the FDA, it was pretty clear they wanted us to go back and run the two arms both with rosuvastatin and atorvastatin.  And it’s a good thing we did.  Because without that, this approval we got in July from the FDA would not have happened.  So we’re very very pleased that that’s in place. 

Now keep in mind, these patients are all very sick.  They’re Type II diabetics.  They’ve had a cardiovascular event sometime within 7 days to 90 days before their first treatment on our drug.  And they all have low HDL, which is a very high-risk category.  So we wanted to really make sure this time the low HDL was maintained, and the contractors have done a good job.  So the trial is an adaptive trial, and it’s to go on until we have reached 250 narrowly defined MACE events.  Major Adverse Cardiac Events.  Death, Stroke, or MI.  So fairly serious categories.  We do follow the other categories for secondary endpoint analysis.  But in this particular program, three-point MACE.  But in this program, hard three-point MACE was also something very convincing that got that FDA approval.  So we’re pleased about that.

Now.  We finally get to put the US flag up on this map.  It took a while.  We’ve operated in nineteen countries around the world, and we’ve already dosed 1,800 patients with apabetalone.  We know this is a very good product.  We know it’s safe.  It’s meeting the criteria as we had expected.  So we’re excited about it continuing to move forward.  I should mention on this slide also that in the last year, we added not only the United States, but we added Russia and we added Taiwan, which was part of our Hepalink deal.

So in the coming year, the clinical estimates.  I’ve got a few up here.  And I put several additional targets exist and the order of launch may alternate.  So clinical is always a moving target.  We have a lot of activity in clinical right now.  More so than we could possibly do ourselves.  So some of it we try to partner, and some of it we try to get others to pay for.  I can tell you that we have some very good success in that coming up.  We do have a lot of interested parties in some of the work we’re doing.  But our first 2018 news should be announcement of the first US patient in the randomized BETonMACE.  And second should be launch of the dialysis trial.  Very well-designed trial.  And BETonMACE full enrollment completed in Q2, maybe Q3.  Fabry’s first patient this year as well.  And top line data for BETonMACE we’re anticipating late next year.

OK.  Chronic kidney disease.  This is a little bit of a busy slide, but I put it up there because this was part of the data that was used by Dr. Kam Kalantar-Zadeh.  He’s the head of UC Irvine Nephrology.  And he did the keynote address at the San Diego conference for the American Society of Nephrology.  He used eight of our slides in the keynote address because the data is that compelling.  And some of that data is what was published this morning in Kidney International.

OK, so that was part of why we launched into the nephrology side in chronic kidney disease.  And some of the others are right here.  This was a very exciting trial for us.  We announced this.  This was one of the five great successes that I had on the list earlier for the year.  We announced this in – I believe it was February.  Where we took two cohorts, eight patients each.  Both of them were on drugs, so there were no placebo patients in this trial.  The first cohort had low GFR (glomerular filtration rate [he said flow]) so their kidneys were pretty plugged up.  They’re getting to the stage - at about 15 GFR, you’re on dialysis, so this is probably Stage IV chronic kidney disease patients.  So we matched them with healthy volunteers that had GFR over 60.  Same age, same sex, same weight basically.  So you got a pretty good cross section.  And then we dosed them with Apabetalone.  And we were able to go in at different time points and analyze what’s exactly going on.  We did two major studies here.  One was pharmacokinetics, so how much of the drug is absorbed?  Is it different in the sick patient than the healthy patient?  And the answer was no, it’s the same in both.  

 And the main part of the study was called proteomics.  So we analyzed 1,310 proteins to see what’s going on at baseline, what happens after the drug in both the healthy and the sick.  And the results were really quite amazing. 

 At the very beginning, at baseline, the sick patients had 288 proteins in plasma that were different than the healthy volunteers.  And after dosing, after even just one dose of apabetalone 152 of those were re-regulated, mostly down (red is up, blue is down).  So what you’re looking at is in the healthy volunteers it didn’t change.  It was almost identical to baseline.  So what it proved to us for the first time, is, that sick patients, proteins get all out of whack.  So I described to you how the DNA from before the protein, they’re changing.  They’re getting sent a signal, they’re making too much, or too little.  Because the body has this domino effect.  There’s some disease factor somewhere and it’s overcorrecting.  So we put it back to the basal level.  And what this proved was that by correcting these 152 in the sick patients, and having very little if any effect on the healthy patients, that was the first time that anybody had any really concrete evidence in epigenetics of just how powerful and how effective this is.  So it’s helpful to us, because complement, which I mentioned earlier and talked about a bit – as I said, it involves invading pathogens.  So if we’re lowering complement too much, it would not be a good thing.  You would be getting high infections and infestations.  We’re bringing it back to the basal level.  So complement you want in the middle.  You don’t want it too high; you don’t want it too low.  So for us, we’ve been able to show clearly with this data, and we’re showing it also with the clinical data where we’re showing a clean safety profile.  We have gone in and analyzed in past trials, the infections and infestations vs. placebo.  And they were always lower in the treated patients.  So we do not have that problem.  Some drugs out there have that problem, and they’ve built some pretty good companies on a drug with a problem.  But we do not have it.

So this is just an example of what some of those proteins are.  And they’re broken down into some of the categories.  Like these are inflammation related markers, these are cell-adhesion-related markers calcification remodeling markers, thrombosis.  Now the old approach to drug development, and this is why it’s great to be ten years ahead, but sometimes it’s difficult...the old approach for a pharmaceutical company is to go in for a single target, like IL-6, and use that as the approach for your drug to lower that, and see if you can cure a multi-factorial disease.  It hasn’t worked so far.  So when we have a drug that is doing every one of these all at the same time, as opposed to approaching one, I think we’re on the right approach here.  And time will tell.  And as you can see, the p values and statistical significance, they’re pretty solid.

So, going forward, we designed this trial.  It’s a cross-over trial it’ll have about 30 patients, CKD patients.  And we do hope to launch this in Q1.  It was a little hard to do on time last year when we were so busy working on $100 million in financing to remove the debt and move forward.  It’s a lot easier to maneuver and operate right now, I can tell you.  So patient is either on drug or placebo and they cross over.  And these patients will be dialysis patients.  So we’ll get a pretty good understanding here.  And most dialysis patients, the thing that finally does them in really is cardiovascular.  So trying to lower these cardiovascular events as an eventual endpoint is important.  This particular trial the endpoint will be alkaline phosphatase reduction, which is an important biomarker in nephrology.  And I can say that in our last 5 or 6 consecutive trials, every one of them has lowered alkaline phosphatase to a statistical significance of 0.0001.  So we’re very confident in doing it yet again.

And thanks to Kam Kalantar and Ken Lebioda working together to put on put together this very prominent clinical advisory board.  This is the who’s who internationally of nephrology.  And when they saw our data, they formed their own committee, and designed trials and worked on follow-up and stuff.  And co-authored and worked on the paper that was released this morning.  So I haven’t even read the paper yet, but I’m told it’s good.

So, follow-on compounds program, I get asked about that a lot.  We’ve always spent a lot of time on that.  These are some areas that you can expect to hear further activity about in the near term:

Pulmonary arterial hypertension.  I talked about that one at the last AGM.  We were approached by a University who wanted to do a bunch of work free.  Ended up being three universities doing it.  And they even collaborated on it.  They’re writing a major publication on this now.  And there is even discussion about funding for that trial.  So that’s exciting, that’s good to know.  

Muscular dystrophy /the FSHD (Facio Scapulo Humeral Dystrophy).  Again came to us from a university.  We’ve advanced this one nicely.  We’ve been working on an alternate approach for delivery of the drug.  So it’s difficult with one drug, if you’re trying to get into multiple indications because pricing becomes an issue.  Here, we believe we’ve worked out a way of topical delivery.  So an ointment that you would rub on the offending muscle area.  And we’ve continued to push that forward.  Bunch of more work to do on it, but what a major advancement if we pull that off.  And it is looking quite good. 

Fabry Disease.  We’re ready to go on that.  And that is a Q1 opportunity. 

Neuroinflammation.  Good potential there.  But I wouldn’t put it high on our list because of the difficulties of that.  Very interesting studies and reports coming out on that.  So we’ll stay tuned. 

PNH/Paroxysmal Nocturnal Hemoglobinuria and [Aus?]  Are the two, these one’s here, those would be the complement related diseases.  I think we’re finally close to getting a PI on that.  But competition is going to be tough. 

Chronic Kidney Disease:  I’ve talked about that already.

HIV -1 Latency: And this the one we announced this morning. 

This was not our publication, but a very major publication, so it was good to see.  And what that publication talked about was re-activating HIV-1.  So, you know about the AIDS cocktails and all the drugs they take.  What happens is HIV-1 goes into a latency or a hibernation kind of state.   And it is actually so small that it hides out in the DNA.  That’s pretty small.  So they believe the approach to fixing this problem is to chase it out of there and that’s why this university did this study.  And there’s been a few other studies done.  But this was done specifically with our drug.  And you note the PFI, that’s Pfizer, and the data looked better for us.  So that was good.  And this is a drug that’s further along.  So we will look at it.  And it would be quite a nice opportunity should it pan out.  Because that’s not exactly a small market.  These patients have to stay on these drug cocktails for life.  If they stop it, the virus comes back.  So the goal is to eradicate the virus.

Now just to touch on some of the points here.  We’re a phase III company.  And that’s a pretty good reason to invest in it.  We’re rapidly approaching the end of Phase III.  We’re a market leader with significant potential.  There are over ten million patients in the top seven markets only just with our lead indication.  So that’s a pretty solid number.  We’re advancing development in other high risk areas like dialysis in CKD, Fabrys. We have an orphan indication that may or may not work out next year.  But if it does work out, it will be early in the year, and we’re excited about that.  We have a very well established safety profile.  1,800 patients is huge.  That’s ten times what it takes to get an oncology drug approved.  So we’re pretty happy about that.  And we have a proven track record for funding and development minimizing shareholder dilution as much as possible.  When we borrowed that 68 million dollars in stages, we were low on the stock price.  The first time, we were about 60 cents.  So financing, if we could have even gotten it at that time would have been at about 40 cents with a full warrant.  So the dilution of financing in the past or after using cheap money for five years, no contest which was most favorable. 

I’m looking forward to next steps.

So on that note, I will close down the presentation, and I would like to thank the people on line at the web cast.  So thank you very much for your participation, and talk to you soon.