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Zenith's BET Inhibitor ZEN-3694 is Currently Being Evaluated in Multiple Oncology Clinical Trials

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SLIDE 1

My name is Don McCaffrey, I’m Chairman, President, and CEO of Zenith Capital Corp.

 

 

SLIDE 2

We’re going to go through the corporate profile, who we are, some of the trials, and there’s a lot going on with this company. It is getting very exciting. In the United States last week, when people were talking about who is the top epigenetics company in the world, it is Resverlogix, but a lot of people think it’s Zenith. So either way I like it.

 

 

 

SLIDE 3

OK, here’s the share structure. We were spun out in 2013, private company, a fully reporting issuer. So we are basically a public company that just doesn’t trade yet. It’s been hard to imagine being a trading company yet because we needed certain aspects to happen before we can move onto the market. If I’d moved this company onto the market last year, the first thing pretty much everybody in this room would have done was sold half your shares. So we need some really good momentum points, and I think we have those now, so we’re looking forward to the status here.

 

 So we have now raised over 50 million dollars. There is more to come shortly. We’re working on some licensing equity component, very similar to what we did with Hepalink in China and also in China. So it takes a little longer to get deals completed there, but you can expect to see something fairly quick.

 

 And our last round was done at $2 US per share. I know our famous Canadian banking system shares will show anywhere from zero to forty cents, or I don’t know some of them even showed a dollar for a while so that was really nice, but I don’t know what it takes to get then to show the true value of $2.60 a share is where we did our last financing at but we keep working on it.

 

 So our estimated enterprise value now, assuming $2.50 a share is 325 million. So that’s quite a bit. Shares outstanding are fully diluted 142 million.

 

 And the cash burn rate here thank God is a lot lower than Resverlogix. So it goes a lot further. The trials are a lot smaller and cheaper. So the dollar goes a lot further and the regulatory moves a lot faster.  

 

SLIDE 4

Ok now, so 

 

SLIDE 5

Epigenetic mechanism. It’s only fair to go through it for everyone.

The writers and erasers are the old time. And the new is the readers.

We’re seeing very clean tox profile.

And seeing some pretty solid results going forward.

Again the readers are important, as I’ll show you later

 

It’s important to knock out bromodomain 4, because it’s being used by the cancers to mutate. 

 

SLIDE 6

And that’s actually shown right here.

So these super enhancer sites were discovered by Rick Young’s lab

   at Harvard just about three years ago.

And what they are, they are a cluster that attracts oncology genes.

So say one of these genes is a cancer and it gets attacked by a drug target.

The cancer switches to a different gene, because they’re clustered right together.

And how do these clusters form?

Well they form because you get a cluster of BET bromodomain 4.

They’re called super enhancer sites.

So again, knock out the bromodomain 4

And the cancers, whether it’s being treated by chemotherapy or anti-body therapies or hormone deprivation or signaling inhibitors – all of these become resistant after a while.

And that resistance is using BET bromodomain-4.

So instead of being the typical approach in oncology that these guys are using where

predominantly they’re very cytotoxic or poisonous to the oncology cell.

They’re very cytotoxic approaches.

 

We have those capabilities, and they’re beneficial to our drug -

But our real strength is the resistance mechanism

So as you’ll see, our working with existing drugs to make sure that they last longer,

That’s our real strength. That really makes us stand out from the crowd in drug development.

If we were just another immuno-oncology drug, we’d be one of about 800 in clinical trials.

 

There are literally 300 clinical trials for Merck’s Keytruda alone.

I can’t imagine running 300 clinical trials.

But we stand out,

Because no matter what drugs we’re dealing with, if we can make them last longer,

we’re ever-greening that pharma’s revenue.

 

So instead of going in and trying to compete with them showing

Oh, we have a better drug than you have,

Even though you just paid 14 billion for it why don’t you just drop that and sell this one –

That’s a pretty tough sell. 

 

But when we can go in and saying look we can make more money for you

 because our drug makes the patient stay on drug longer, and it’s a synergistic benefit for the patient.

So that’s what we’ve been trying to prove.

I think we’ve done exceptionally well with it.

 

 

SLIDE 7

Basically this is the approach we’re talking about, is

Taking drugs that are current multi-billion dollar drugs

Whether they’re PD-1 or PDL-1 inhibitors, or PARP inhibitors, androgen receptor type of drugs,

And increase the duration of therapy so they get more responders and they’re on longer

This differentiates us from the entire market

And believe me going in and talking to a pharma about combining with their drug

and making their revenue last 2 or 3 or 4 years instead of just 2 years, that’s a much easier sell 

 

SLIDE 8

So we started in prostate cancer 

 

SLIDE 9

We had some very early solid data showing that our drug in combination with Pfizer’s Enzalutamide really made the drug work a lot better.

That’s what this is depicting here, and now we’ve seen it in humans.

So Enzalutamide and Abiraterone are the two key prostate cancer drugs right now.

And between them they do 6 billion dollars a year in sales.

So that’s great, but the bad news for them is, whether it’s Johnson and Johnson or Pfizer is

after two years those patients become fully resistant to that drug.

So how about after three years or longer?

And that’s what I’m going to show you today.

And we already have shown the major pharmas our data, so it has been exciting times.

And some of it has recently been published.

 

SLIDE 10

So there are at least four major resistance areas that form in these cancers.

We tend to think of prostate cancer – that’s one cancer.

But prostate cancers can be dozens of cancers.

I think a good example that I heard a couple years ago was the hematological cancers or blood cancers.

About 50 years ago we considered it one. You had leukemia.

About 10 years ago it was 89. What it is today, I’m not even sure, it’s probably over 100.

But they’ve been reclassified into what they really are.

So you’re not going to have the same resistance mechanism in every patient.

However BET bromodomain mechanism is actually involved in all four of these major resistance avenues.

So knocking out bromodomain 4 is really reducing the chances of the cancer metastasizing.

 

 SLIDE 11

OK, in Phase I

 

 SLIDE 12

We put together a star-studded panel of principal investigators.

And I’m always saying this. When...

If you guys are investing in other biotechs, look at the clinical trials.

Figure out who the principal investigator is.

And no offense to Olds College, but if it’s Olds College, run.

And if it’s the head of Memorial Sloane Kettering or UCSF you got something there,

Because these guys have their choice of any program to look at

And I got ‘em both.

Neither one of them had ever worked together before.

And this one here, Eric Small, he developed Abiraterone.

Howard Scher, he developed Enzalutamide.

Those are the two key drugs in the area.

And who are they working with now for the first time? Us.

So that’s pretty impressive.

 

The other centers are all good as well.

UCLA has done a fantastic job for us.

And just published a paper that came out only days ago that’s changed your world, believe me.

 

 

SLIDE 13

So this was the result of Phase I, it was really designed as a single agent study.

And again, our approach has always been combination.

So you have to do a single agent first to prove it’s not toxic and stuff.

And we had some pretty good results with that.

We reached our maximum tolerated dose, which we’ve now exceeded.

We had good pharmacokinetics with the dose

We had safety,

Target modulation we had

And we had some single anti-tumor activity as well.

 

 SLIDE 14

This is a patient on there and we went in and did radiographic studies as well

As you can see the two of them here showing that even after 32 weeks there was no change in the tumor.

 

 

SLIDE 15

But we’re getting better and better at this

And in the new trial

 

 

SLIDE 16

This is very exciting data.

So I’m going to describe this for you

The blue line here is what normally happens.

So what’s going on on this very busy chart

Is at the far left side, every one of these patients has already become resistant to either

  Abiraterone or Enzalutamide

And what we do then, is we switch them to the other drug.

So whatever they were on, they get the other one

This is standard protocol in oncology procedure right now

And usually that patient lasts about another fifteen weeks on average,

and then they become resistant to the second drug.

So fifteen weeks doesn’t sound like a lot, but if it’s your life, you’re going to follow the protocol

Because you get an extra 15 weeks before you have to go on hard-core chemo or something like that.

So that is the normal. This is the average standard of care industry line.

We set an artificial target of twice that line.

Look at these guys here.

Like some of these guys, it doesn’t work on them.

So we do studies to try to find out why.

It’s part of that story that not all cancers are the same.

So these guys are all in a prostate cancer trial,

but they all don’t have the exact same kind of prostate cancer.

So this second cohort here, this is actually an older slide deck, they’re out over 75 weeks already

And their PSA scores are below one

One of them we’re going to highlight here in a minute

Because UCLA did a major publication on him

And that particular patient’s tumor is actually 80% smaller than it was before

Tumor regression in prostate cancer is almost unheard of.

So that is pretty amazing

So we have a few of these guys that already have tumor progression -  or regression sorry

And many of them,

These guys up here all just started late, because they’re at higher doses

So this is the lowest dose, second lowest and on you go

So you can see how many of them are already past the average line – way past

And we work with this drug as we go too

Like one of the only side effects we’ve seen is

Oh – I’m never going to get this one right -

It’s a photo thing in the eye where the eye becomes light sensitive

So about 74% of the patients have this - that’s probably the worst thing we’ve seen

And it’s no big deal.

Give them the pill at bed time instead of in the morning and it solved the problem.

Pretty simple solution.

But there are all these little learning curves like that.

And what kind of drugs they were on before this.

We’re learning how to even make these numbers better and better.

Now when you compare this to other oncology drugs.

I mentioned Merck’s Keytruda drug – which is a blockbuster drug for them.

It’s in 300 clinical trials.

It only works in 20% of people. And that’s considered blockbuster.

Because those 20% used to die and they don’t now.

That’s the drug that saved Jimmy Carter’s life.

He’s lucky. He’s one of the 20%.

So to see these kinds of results already

And everybody’s still going strong down here

So we’re quite pleased with that. 

 

SLIDE 17

And here are some of the PSA scores.

I took just these three patients who are out the longest.

This is their PSA scores.

So we dropped it way down with our drug and kept it down.

And they’re down below 1, still and chugging along on drug.

And so far no issues. So...

This is only showing 56 weeks, but they’re out 75 plus now.

So as you can tell, and the bottom chart here is talking about

These are patients on Abiraterone, that’s J&J’s drug

And what happens to their prostate scores, PSA scores

While as ours dropped quite a bit.

PSA doesn’t work in all patients but it is a good monitor to use. 

 

SLIDE 18

Now this was exciting.

And I know some of you do an inordinate amount of research on these two companies.

Do yourself a favor and research some of the names on that author list.

Especially the ones in the middle. (Silverman to Belldegrun)

I think you’re going to be highly highly impressed by who they are.

This is a who’s who in the field.

Not only in oncology, but in successful biotech companies.

Multi-billion dollar successful biotech companies.

So what it was was studying one of the patients at UCLA

Who was on drug in combination Enzalutimide and our drug

And they used the most advanced artificial intelligence program in the US at UCLA

To monitor what was going on and which drug was having the impact

And the drug that had the profound impact in lowering his PSA score was ZEN-3694

They published this last week. It’s actually really cool

A lot of it’s above and beyond me, but  

 

Article:

Pantuck, A.J., Lee, D.K., Kee, T., Wang, P., Lakhotia, S., Silverman, Michael H., Mathis, C., Drakaki, A., Belldegrun, A.S., Ho, C.M., & Ho, D. (2018, September) Advanced Therapeutics Modulating BET Bromodomain Inhibitor ZEN-3694 and Enzalutamide Combination Dosing in a Metastatic Prostate Cancer Patient using CURATE.AI, an Artificial Intelligence Platform. Advanced Therapeutics   www  dot  advtharp  dot com

 

SLIDE 19

They were shooting for this sweet spot that they had here

That the better it was

So what this is showing was that on Enzalutamide alone,

this patient’s PSA score would never have been below 10

And we have him down to 0.6

So that’s a pretty impressive move and long term

Not just a temporary blip, long term.

If the patient took less of our drug it went up.

If he went back and took more of our drug it went down.

So it was modulated the whole way along.

And again, this is the kind of data that big pharma wants to see.

So up until now they’ve been saying “how do we know it’s not our drug?”

“How do we know it’s not our drug?”

Well, now you know it’s not your drug.

So it’s a big selling point for us.

So the two things we needed were longer duration of patients our drug.

And we’re out pushing about 80 weeks now and we’ll just keep them on.

And this type of hard core publication from UCLA artificial intelligence program.

 

 

SLIDE 20

That’s pretty exciting stuff.

 

 

SLIDE 21

So we continue on to the next steps

Because we have the one drug in this category that is clean

The other drugs all see thrombocytopenia.

That’s thinning of the blood. You can bleed out with that

That’s like taking too much rat poisoning or warfarin or those types of things.

We don’t see that.

And we don’t see poor pharmacokinetics.

We have very good pharmacokinetics.

And we didn’t use a conservative strategy going ahead.

So as some of you may remember

We started out about two years behind all of the other companies in BET bromodomain oncology.

They were in hematology.

We were originally going to do hematology.

Then when we had that choice of drug turnover because of intellectual property issue.

We were two years behind everybody.

We’re two years ahead of everybody now.

And we’ve certainly gained the attention of the pharmaceutical companies

  that we know what we’re doing in drug development.

And it’s pretty exciting.

The feedback we got last week I wish I could share it with you.

Actually I will share it shortly with you, but can’t do it today.

But pretty exciting stuff coming our way.

And again we got on-target tox profile,

We have a safety profile that’s really good.

Focused clinical.

We’re into solid tumors.

We’re in it ahead of everybody.

These guys had to start at really low doses

 because they have thrombocytopenia and GI stem cell tract issues and? HERG?

So they can only dose for two weeks and then they’ve got to take a week or two off with a patient.

Let them build their blood platelets back up. Then they do it all over again.

We don’t have that.

We have engaged target, which they don’t even have at their level.

So we have a lot of advantages here that have helped us move forward quite fast. 

 

SLIDE 22

Now I’ve shown this slide before, but it’s just to remind you that

We have already done numerous other-drug combinations with ours

Everything below the line here, line one, means there’s some positive synergistic effect with the particular drug that’s listed in the color codings here.

And we’ve done a lot more than this now

Some of them like the PARP inhibitors, the checkpoint inhibitors, all these drugs that are so popular in oncology right now.

We make ‘em work better and we help knock out the resistance mechanism.

This is a really good approach

So instead of going in and saying oh my drug’s better than this one or this one and this one.

We go in and say we can make your drug work longer and harder and better.

That’s a much easier sell.

And the data’s there to prove it already.

And having that UCLA publication come out was pretty spectacular.

 

 

SLIDE 23

Now what wasn’t on that list is PARP inhibition

This is becoming a very popular area.

And I hope to be able to publicly inform you in the next few weeks

That we’re going to be involved in this area and

the PARP inhibition we will be using in Triple negative breast cancer.

It is a very aggressive deadly type of breast cancer

And all of these publications, all three of them highly suggest that

A PARP inhibitor and a BET inhibitor are going to have a major impact in triple negative breast cancer.

So again we’re getting a lot of attention

And going forward into that program we hope to announce shortly that we are partnering our way through that one.

So stay tuned

It should have been a September 12th announcement.

We’re getting there. 

 

SLIDE 24

Anyway, How about we go on to the Q&A

And we have the microphone as well so uh... 

 

Q Yes Don I’m a little confused with talking about the BRD-4 in the Zenith study.

Because I thought it was selective with the other drug.

But in this drug, I thought it was a pan-BET inhibitor so it wasn’t selective.  

 

A Yes I can clarify that for you. So the selectivity is BD 2. (BD2-BRD4)

And I apologize for all the crazy names, these medicinal chemists,

I’d hate to see what they name their children, because they really make a mess of these things.

BD-2 is where our selectivity is with Resverlogix.

But Zen 694 is a pan inhibitor. It covers across the board.

So we’ve found and so have the others

that a pan inhibitor is probably more effective in an oncology setting.

But having the ability to be BD selective as we are at Resverlogix,

Now that definitely put us ahead of the world

There’s finally after, I don’t know how many years we’ve been public with that,

But finally someone else has a BD-2 selective compound

Don’t know if it’s going to go into clinic or not, or maybe it already is

But we’re way ahead of them.

And they’re in oncology only

It’s a Gilead program

 

 

Q: Don, if Zenith Epigenetics is sold being a subsidiary of Zenith Capital is that a material change to Zenith Capital and does it require a shareholder vote?

 

A   No. So the sole owner of Zenith Epigenetics is Zenith Capital Corporation. And the existing plan as always has been, at the time of an M&A transaction, should that be what it is, we would in parallel or just before dividend the  Zenith Epigenetics shares out to the corresponding shareholders. And we don’t want to do that now because it’s a taxable event. And I don’t want to pay my share of the taxes yet, not until there’s money to pay the tax. So. Any other questions? Yes Dave.

 

 

 

Q: You had said earlier that you’ll have to raise some more money. Was that with the partnership or will we be getting a little more dilution.

 

A: It could be either way. We have the ability to raise money by doing licensing programs as I mentioned. The China type of licensing deal. And as I showed you earlier with Resverlogix, yes we had dilution last year 39%, but we also had a 364% stock increase. So dilution isn’t always your enemy. Heh – he wants the mike back. I think he disagrees. (chuckles).

 

Q: It is an enemy when your royalty gets chipped away.

 

A: There you go. Any other questions? Yes EJ 

 

Q:  Don I’m just curious about the CURATE.AI program that took place with one patient. The reason I ask is it sounds almost like targeted individual personalized medication.

 

A:  Personalized medication. Yes it is. It’s a great approach. We’re talking to them about doing other patients. But as you can imagine, they own that technology and they’re talking to us about paying for it. I’d like the free part. I don’t know about the paid part.  They’re still need to prove it up so we might get some additional there, we’ll have to wait and see. It’s unknown at this time. Yes Rick. 

 

Q: Don what is your preferred deal structure if somebody like J&J or Pfizer steps up and either wants to buy the drug or the whole company.

 

A: Cash on the barrel? As far as preferred structure we don’t need - I mentioned J&J and Pfizer because they own those two drugs. But that doesn’t have to be who buys the follow-on drug. It could be anybody as long as they have a solid oncology program and good sales force that type of approach, but my preferred would actually be a straight M&A transaction. In order to sell 3694, what would be required is only three of the patents held by Zenith be left in Zenith Epigenetics. Everything else could be left in Zenith Capital Corporation. So with those there patents they would have what they need to run the entire program, but not necessarily take all of the IP.   

 

Any other questions? One last question. No? OK very good. Thank you very much for coming out and my staff and I will be hanging around to answer any additional questions. Any that we can answer. And uh, thanks again. Take care.

 

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