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Message: Zenith Epigenetics 150513 Conf Call

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SLIDE 1

At this time, I would like to turn the conference over to Mr. Donald McCaffrey, President and Chief Executive Officer. Please go ahead.

Good day. This is Don McCaffrey, I am the President and CEO of Zenith Epigenetics, and I’m here to deliver a corporate update. We will try to make this a quarterly event going forward.

SLIDE 2

On slide two, this is the list of today’s agenda. And we’ll be covering areas such as the Corporate structure and historical review of the company (what’s transpired in the last few months), the epigenetic review and clinical planning ongoing, the Zenith competition, discovery and development opportunities, and we’ll also touch on the Zenith capital structure and financing and we’ll also go into the Zenith milestone targets.

SLIDE 3

Now on slide three, the share structure profile. Most people know that this company was a spinout from Resverlogix in June of 2013. It is a private company; however, we are very strongly considering an IPO. Hopefully we can arrange that in 2015 yet; that will be market-dependent. Cash raised to date since the spinout is 15.3 million dollars. That has all been raised at one dollar U.S. per share.

Enterprise value of the company is approximately a hundred million. Shares outstanding a little over 94 million (94,463,613), and fully diluted just a little over a hundred and five (105,106,643).

And the burn-rate is around two million dollars per quarter at this time. It will increase as we go deeper into clinical trials.

SLIDE 4

Now on slide four, the historical timeline and strategic progression of the company, Zenith started inside Reserverlogix, so the history goes back quite a few years. But in the last two years, in particular in 2013 and 2014, the biology advancements and understanding of BET bromodomains and epigenetics have really given Zenith a lead against the competition. As you’ll hear in the slides today, we do have quite a few advances that the others just aren’t aware of yet.

Also, last July the FDA approved an IND for human clinical studies, so we’re very pleased with that. And they did so without the extensive monitoring reviews required of all the competitors. So our non-benzodiazepine chemical scaffold was very advantageous and the FDA recognized that.

Now we also brought on the number one oncology unit in the United States. They accepted the lead position as principal investigator, and that’s the Memorial Sloane-Kettering (September 2014).

The challenges we faced, I think most people on-line know what and when some of those were. But prior to our Phase I launch, literally days before we dosed our first patient, we had an intellectual property issue arise. Now, that issue was kept quiet for business development reasons. A patent from another company was filed that pre-dated ours by a few weeks. So we decided as opposed to fighting it and seeing if we could work around it, we’d utilize our very large intellectual property portfolio and move forward. And that’s what we did. We don’t have competition on that particular molecule because we were quiet. You can think of it as years ago when Blackberry had their issues with the patent trolling that was going on causing them problems. The issue is not identical, but it was easier for us to go in and redevelop. So that’s what we did on the bottom line. Change of plans. New intellectual property was then published in January of 2015, allowing us to move forward with second-generation compounds that will not have patent issues going forward. So the strategy was to come up with at least two compounds. And we have done that, we have selected our lead compounds as of April. They will be Zen 3694 and Zen 3717.

So the shareholder future revenues, the teamwork portion of this slide. This is where a lot of people are not familiar with the huge advance Zenith actually just made as a result of the Resverlogix China licensing deal. When we split the company, the royalty streams for RVX-208 are a flow-through to Zenith Epigenetics. So that China deal is very beneficial to Zenith shareholders.

And the future course, through internal development, regional licensing, co-development deals, we will fuel value creation over the next couple of years.

SLIDE FIVE

Now moving on to slide five, this is a part of our past, some of the work we’ve done to validate the work we’re doing with these epigenetic mechanisms in animal models and in human cells. This is a slide I’ve shown before, but it shows very clearly that this Zenith molecule was able to eliminate the cancers as opposed to vehicle or standard-of-care treatment with Cytarabine.

SLIDE SIX

This is also an older slide showing the development of tumor regression. Where ours, being the green line, showed that in all twenty of these mice, we were able to completely eradicate the tumors. And these are very aggressive tumors, AML cancers, Acute Myeloid Leukemia. The red line is one of the competitors showing that if you stop taking their drug at twenty-one days, as we stopped ours, that theirs comes back, the tumors start to grow again, and same with vehicle. So this is treating these mice for twenty-one days, and stopping, and these tumors were eradicated. So it’s telling us that our approach is very solid.

SLIDE SEVEN

Slide seven extends that into human cells. The top line of five patients were all cells donated from patients with AML cancer. These were tested in petri dishes. As you can see the final three of them were very effective in killing the cancer lines. Patient two also was very effective. Patient one - not as effective. And you see the two red stars in patient four. Those are very interesting, because they show that the standard-of-care drugs idarubicin and daunorubicin, that those patients were already resistant to those drugs right from the very beginning. So it’s very strong support for BET bromodomain inhibition.

(Question: What was the Mitox line?)

SLIDE EIGHT

Agenda slide.

SLIDE NINE

Moving to slide nine, we have a little review of epigenetics. So we are the modern, advanced end of epigenetics. Some of the ten-year-old versions of epigenetics are erasers and writers. And they are a chemical-to-chemical interaction, dealing with putting something on or off the end of the histone tail. Whereas we are a protein-to-protein interaction, changing what happens in the cells and in the proteins that are targeted. So we believe that approach is one of the reasons why we see less toxicity than with some of the other approaches.

SLIDE TEN

So on slide ten, Zenith BRD-4 target is discussed, and it is directly involved in the resistance mechanisms of several types of anti-cancer therapies. These include signaling inhibitors, hormone deprivation therapies, anti-body based therapies and chemotherapies. So what happens is, as the therapies continue, they get less and less effective. And it’s believed that the reason for that is that the oncology gene that is being attacked, say it’s a Bcl-2 or a C-Myc, they’re eventually changing sites. And they can do that through what are called super-enhancer sites. Now BET bromodomain has the ability to reduce those sites, and reduce the effectiveness of where the cancers are actually escaping. So the resistance mechanism is involving the BRD-4.

SLIDE ELEVEN

Now let’s go to slide eleven. We’ll discuss a little bit more about how that advances our technology and how we can take advantage of it. BET inhibitors have important potential to be important combination agents with existing therapies. And what that means is that by delivering our drug with existing drugs , in this slide you see combination treatment potential with over twenty different drugs, in lymphoma, AML, lung cancer, prostate cancer, breast cancer, and melanoma. What we’re trying to do is make sure that those drugs maintain their effectiveness, and the escape mechanisms are reduced or completely cut off. So this also allows us to do different combination deals going forward as well, with any one of these drugs or others that are on the market.


Lymphoma

· Rituximab

· Ibrutinib

· CHOP

· Bortezomib

· Everolimus

Melanoma

· Dabrafenib

· Trametinib

Breast Cancer

· Tamoxifen

· Everolimus

· Cisplatin

· Olaparib

· Trametnib

· Lapatnib

· Olaparib

Prostate Cancer

· Abiraterone

· Enzalutamide

Lung Cancer

· Trametinib

· Crizotinib

· Everolimus

AML

· Cytarabine

· Idarubicin

· Panobinosta

· Quizartinib




SLIDE TWELVE

So on slide twelve, we’ve investigated those potentials a little bit further by studying the progressed biology and the unmet needs. We’re really looking at indications that have targeted patient subsets. So that’s AML, that’s DLBCL (that’s lymphoma), breast cancer and prostate cancer. As you see under them, there are different sub-sets. Because the BET bromodomains are very well situated for working on subsets. So you’re actually analyzing the cancers and determining in advance the ones that are most likely to be positively affected by our drugs. So there’s a clear registration path for all of these, and there’s a potential for proof-of-concept as early as Phase I, because they are so targeted. We should be seeing results. There is huge unmet need in each of these areas, all four of these. And the key opinion-leaders that have reviewed our data are very excited about it, enthusiastic and support going forward as quickly as we can. Especially in prostate cancer, the results have been very encouraging. So we look forward to moving that as quickly as we can.

SLIDE THIRTEEN

You’ll see on the next slide, on thirteen, some of the development plans for our first lead molecule, which is ZEN-3694. We hope to stay on track; we’re on track for an IND being filed by the end of 2015. And top investigators have already lined up to support this. As in the last go-around, we are very pleased to see that the key opinion leaders and the key investigators around the continent are very excited about this and we should have a very solid program moving forward by the end of the year. Now moving forward means getting into the dose-escalation phase in 2016. That will include solid tumors and lymphomas. And from there it really picks up the pace, it could split up into five, six or maybe even more different cohorts or expansion cohorts dealing in specific types of lymphomas or solid tumors. And, as I’ve highlighted in the yellow, the combination program also adds quite an ability. We believe that the drug will work very effectively on its own, but in the cancer world, there are a lot of combination therapies ongoing, and that’s probably a wave of the future, so it is an area that we’re studying quite a bit.

SLIDE FOURTEEN

Agenda slide.

SLIDE FIFTEEN

Now moving on to slide number fifteen, we have a historical list of some of the epigenetic deals. So we want to talk about our competitors here. Epizyme, Constellation and Oncoethix. They have all done very good deals in the last two to three years. Whether they are all writers, readers or erasers. A couple of these are readers as you can see. The most recent deal was actually done by Oncoethix and Merck; it was done in January of this year. It’s a very interesting deal $110 million up front and $265 million more with clinical milestones. So they are valuing these markets quite nicely.

SLIDE SIXTEEN

Slide sixteen shows the second-generation advances that we have obtained as we move into the clinic. And most of those focus round the drug’s selectivity, our understanding of it, and the autoimmune program that we have active, and the covalent binding program as well. Whereas none of the historical competitors here actually have those programs that we are aware of. And we also distinguish ourselves crystal clear on scaffolds. That we have multiple scaffolds and none of those are benzodiazepine. The other scaffolds are exclusively benzodiazepines. That is actually a sleeping medication and they have had some cardiovascular issues going forward.

SLIDE SEVENTEEN

So on slide seventeen let’s look at one of these in particular, and that is the Oncoethix molecule. We like this deal that was done because it is for a single molecule. The company does not have a scaffold, it has a molecule, and as far as anybody knows, no backup program. So a $375 million dollar deal for a molecule makes a platform company like Zenith quite excited. And as you see here in the dashed red box, that in comparison against a Zenith compound, we are seeing a doubling in the tumor growth inhibition. Of course, that’s your main goal, so we are already convinced that our technology is far superior and look forward to moving it into the clinic.

SLIDE EIGHTEEN

On slide eighteen, we can talk a little bit about the opportunity we have to lead the second-generation programs with their larger markets, the combination efforts that can be done and regional deals. So what we’re trying to depict here is that the top of that iceberg is the current clinical programs. And they deal mainly with hematology malignancies and they all have had extensive CV monitoring added to their program. So that’s where we believe we have an advantage of being a non-benzodiazepine as I point out in point two there. And this gives us plenty of expanded opportunities enabling us to go into solid tumors, autoimmune and second-generation hematological malignancies. On the right hand side, please also note though that in with the second generation there are new players in the field with Bayer, Gilead, BMS, Incyte and Abbvie. So the field is getting a little busier, however it is an enormous field. Bromodomain inhibition is going to be a very big area. So in our efforts moving forward, we concentrate mainly on areas where others aren’t working. So that will distinguish us from the field.

SLIDE NINETEEN

Agenda slide.

SLIDE TWENTY

Now on slide number twenty, we’ll talk about some of the development that has been ongoing at Zenith for the last several months, since our change of plan here. We have developed a gene signature blood assay that measures target modulation in the clinic. I know that’s a mouthful, but what we basically do is we start with 600 genes analyzing them and narrowing them down and down to where it’s six. So we can now assay and validate effectiveness of hitting the targets in the patient’s own blood. So it’s a very effective approach here. It’s a nice method to have, and it’s something that the FDA really likes, as it’s a step toward personalized medicine.

SLIDE TWENTY-ONE

Now on slide twenty-one, we’re going to touch on just a couple of other programs that have been ongoing as we’ve been redeveloping. We’ve been working more and more on the selective BET inhibitors. So that’s hitting the BRD4, BD1 or BD2 selectively. This company was born of technology that was the first-ever selective bromodomain in the world. That was published by the Harvard and Oxford people in the structural genome consortium.

We also have a covalent program, or irreversible BET inhibitors. These can be very helpful in cancer as they attach and stay. So in particular on very aggressive oncology programs this could be a very useful program. We are not aware of anybody else who has a covalent binding program.

We also have, as I mentioned in the previous slide, a target modulation assay and that was completed already and effectively tried on patient’s blood.

SLIDE TWENTY-TWO

The next slide is some of our early opportunities for early revenues, including regional licensing deals and orphan indications. The BET bromodomains are being raised as having very large potential in various orphan programs. So we are going to look at adding an orphan program. And in the regional deals, we are in discussions on early licensing in some of the areas such as China and other areas of the world that normally do off-global deal licensing. So we are seeing some potential of moving forward in those areas, probably sooner than later.

SLIDE TWENTY-THREE

Agenda Slide

SLIDE TWENTY-FOUR

Now let’s talk in slide twenty-four about a private placement that’s ongoing. Financing of the company, where we stand, some of our numbers. This will give you an update. We currently are in the middle of a private placement for qualified investors, around $10 million US. The shares are priced at $1 U.S. per share. The investors have to be accredited investors. The share structure is listed here as well. Current details, about $94 million in shares outstanding, and fully diluted about 105 million. So post the spinout, Zenith has raised $15.3 million U.S. and that was all done at $1 US per share. Now I know there’s a lot of confusion about your shareholdings because every single different bank out there lists them at a different price in the account. But we can assure you that the US $1 is something that we stand by. And the next slide, twenty-five, actually highlights how we come up with that valuation.

(Formed June 3rd, 2013 as a spin-out from Resverlogix; Outstanding shares 94,463,613; Issued warrants 5,479,440; Stock Options and RSU’s – 5,163,590; Fully diluted – 105,106,643; Pre-money valuation is estimated at around $95 million).

SLIDE TWENTY-FIVE

It’s pretty simple. When you look at some of the deal structures that were done, like number one there on slide twenty-five, Oncoethix being acquired with $110 million up front. Epizyme doing a deal with a $90 million dollars up front. Constellation doing a deal involving $95 million up front. And of course, when we separated Zenith epigenetics from the public company Resverlogix, the Resverlogix market cap dropped $90 million dollars for the following month. So that pretty much establishes us in that $90-$100 range. And that’s where we’ve been pricing the company, and it has been accepted very well to date.

SLIDE TWENTY-SIX

Now on slide twenty-six this is the Zenith milestone targets. And you can see the different goals here.

In the Development targets, we already have published the new intellectual property. We have selected the new lead molecule ZEN-3694. We have selected a back-up molecule, ZEN-3717. We are on schedule for filing this IND with the FDA by the end of the year.

(In Clinical targets) We have already been discussing with the top investigators to recruit, as we believe it’s very important especially for the prestige of the program. We will initiate a clinical trial for solid tumors and lymphoma. And we should reach proof of concept by the second half of 2016. That will still be Phase I, but based on how this program is designed we should have proof of concept of the drug working against various cancer targets in approximately a year and change. And we will expand at that point to include combination therapies as well.

So in the Business Development category, we look to do an IPO on the NASDAQ and we do hope to have that launched by the end of this year. Regional licensing deals in China and other countries are in discussion. Co-development and partnering deals are also in discussion. And we have a lot of new BET bromodomain opportunities that we are working on. We don’t list them in particular for competitive reasons.

So on that note, we’ll wrap up today, and I just want to give you an open invite for any questions or anything that you would like. Please feel free to contact us at Zenith Epigenetics. You can ask for Patrick Chu or Sarah Zapotichny or even myself. We’ll be glad to update you on any issues that we did not cover today. Thank you very much for your time. Talk to you soon,

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

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