Please Note: Blog posts are not selected, edited or screened by Seeking Alpha editors.

ZIOPHARM Presentation By Dr. Cooper At The Intrexon Investor Day Meeting

|Includes: Intrexon Corp (XON), ZIOP

Being a ZIOP bull, I, like other bulls, attentively listened to CEO Dr. Laurance Cooper's presentation at the Intrexon's Investor Day shindig last week...Actually I listened to it a couple of times...Then, I decided to have his presentation transcribed...for two reasons: 1) Reading the words allows me to comprehend and appreciate the presentation better, and 2) Since the recording of the webcast is only available for 30 days, I wanted to preserve a verbatim record here for future referencing...and I gotta tell ya, re-listening Dr. Cooper's talk, while simultaneously reading his presentation, gave me a much greater appreciation for what the good Doctor said, and revealed...

For those new to my blog, I want you folks to understand and appreciate the first important fact: Today, in the most exciting field in cancer research, many consider Dr. Laurence Cooper to be one of the world's foremost authorities on immuno-oncology, ...if not #1, then certainly he is one of the top 3 and ZIOPHARM is extremely fortunate that he is the company's CEO...No other company in the immuno-oncology space can boast of a CEO of similar stature!

Another important fact that needs to be understood, and Dr. Cooper pointed this out in his presentation is that ZIOPHARM, because of its ground-breaking partnership with MD Anderson, now has access to years of clinical data that MD Anderson had been conducting in the field of immuno-oncology, and well before its partnership with ZIOPHARM...all that clinical data ZIOPHARM will be able to piggyback on and at a minimum, catch up with JUNO and KITE who have had a couple of years of headstart on ZIOPHARM. Dr. Cooper clearly points out that ZIOPHARM will be releasing some of that data as its own, at the upcoming ASH conference in early December. I cannot stress how important this fact is, and many, if not most folks in the investment community are not aware of...Because with the revealing of this data, and Dr. Cooper hinted, "we have therapeutic optimism," that the data is good, ZIOP will clearly have caught up with its two main competitors, JUNO and KITE, even though, chronologically, it was late to the party!

Before I share the entire transcription of Dr. Cooper's November 12th, 2015 presentation, along with the relevant slide(s), and in the appropriate order, I will first highlight a few salient parts of his talk...

1) ZIOPHARM's Technology and Capability:

i) "Ability to generate cells, NK cells and T-cells, outside of the body, and infuse them into patients. This is done by us in two broad categories: patient-derived cells going into their recipient and donor-derived cells coming from another person, going into the recipient. And those donor-derived cells at the moment come from a match sibling or a match family member, but increasingly, you'll see us starting to put in third-party cells those off-the-shelf applications."

ii) "We can deliver a very potent drug and importantly activate the drug through an oral ligand but also turn off the drug with an oral ligand. Many companies can turn on genes, it's very difficult to turn off genes. It is the on-off regulatory switch that is the critical differentiating component."

2) Multi-Center Clinical Trials:

"ZIOPHARM already undertakes a multi-center gene therapy program. This is -- there's a pause here. This is actually a significant effort by us. There are very few companies right now in the United States that do multi-center gene therapy trials, and we do it. To do this we are essentially now entreating patients who have advanced glioblastoma, a brain tumor. This is a lethal moment in this person's disease narrative, and we are instilling into that brain tumor the weaponized adenovirus for the on-off delivery of IL-12 and you'll see this data submitted in just a few weeks now to the Society of Neuro-Oncology."

Clinical Data: "We are a-l-r-e-a-d-y in the clinic, and we have therapeutic optimism about what our data are for glioma and breast."

On CD-19: "We already have clinical data. These work stems from my work when I was at MD Anderson just a few short months ago in May of this year. Now we finished these clinical trials we will report on this officially at ASH in December of this year."

"We've followed these patients now for two years, and 86% of these patients now are in remission. We have also now infused T-cells that come from a third party. This is a match sibling or a family member. When those cells are weaponized to have that chimeric antigen receptor they are infused, and in this situation, about 60% of patients with ALL now have long-term remission, and interestingly, this is kind of a nuance to the field that we get at ASH, three-quarters of the patients who have had a haplo transplant are also in remission."

Off-The-Shelf Treatments to Help Reduce Treatment Cost: "You'll see us starting to put in third-party cells those off-the-shelf applications."

"And then the off-the-shelf, of course, because underlying all of this is the ability to get products into patients and to do it at low cost, because if the cost structure is excessive it will remain a boutique. So, part of what we do, is not only do excellent science, but keep our eye on the fundamentals so that this biology will be available to many."

I think this is pretty heady stuff!

kp

So here is Dr. Laurence Cooper's presentation in its entirety...

Harnessing the Power of the Immune System to Fight Cancer

Dr. Laurence Cooper M.D., Ph.D.
Chief Executive Officer, ZIOPHARM Oncology, Inc.

Cooper: Thanks so much. Thanks RJ and thanks to the Intrexon team for having me here today. Delighted to be here.

This is my most important slide. So, fact: immune cells can both prevent and treat cancer, but the question I think that all of you had therefore is, why is it that patients with healthy immune systems develop cancer? And, there's really two reasons for that. The first is that the genetic instability of cancer is always constantly progressing inside the body. So you strike with your immune system with precision, but your cancer slips outside of that immunologic pressure underneath your thumb. The second piece is that the hardwiring that is you, yourself, as a human being, in your T-cells and in your NK cells, has failed you when you have cancer.

So, there are two solutions therefore. The first solution is that you need a complicated set or a portfolio of therapeutics to get at the, essentially, the genetic instability. So if you applied multiple points of pressure you can essentially have therapeutic optimism and a sense of cure.

The second thing you need is a programming language. Ex vivo programming language, such as through Intrexon, so that you can genetically modify cells outside of the body, essentially curing what the human body cannot do. And those are the two facets that I want you to take home, is the engineering of the immune system ex vivo and it's the multiple cellular approach and the multiple therapeutic approach which allows you to have a legitimate shot on goal.

Ok, so now, let's just distill this to practice. There are four quadrants. The upper left hand side talks about cell therapy, the ability to generate cells, NK cells and T-cells, outside of the body, and infuse them into patients. This is done by us in two broad categories: patient-derived cells going into their recipient and donor-derived cells coming from another person, going into the recipient. And those donor-derived cells at the moment come from a match sibling or a match family member, but increasingly, you'll see us starting to put in third-party cells those off-the-shelf applications.

The top right hand side addresses another way of manipulating the immune system. Instead of fashioning the cells outside of the body to be therapeutic, why don't we develop a drug that harnesses the immune system inside the body? And, that is used with this weaponized virus, this adenovirus that has Rheoswitch that Tom introduced you to, so that we can deliver a very potent drug and importantly activate the drug through an oral ligand but also turn off the drug with an oral ligand. Many companies can turn on genes, it's very difficult to turn off genes. It is the on-off regulatory switch that is the critical differentiating component.

At the bottom, the other way, essentially, is to reprogram whether it be a virus or a cell using both viral and non-viral technology -- Pete elegantly introduced you to that -- and then of course, marrying those viral and non-viral approaches with the kind of genetic tools that allow you in a feet-forward fashion to design, build, and test. But, importantly, to do it in the human, and to do it expeditiously and at low cost so that you can democratize this process and not be a boutique but really be a solution for oncology.

Here, a few vignettes now about where the clinical program stands.

So, ZIOPHARM already undertakes a multi-center gene therapy program. This is -- there's a pause here. This is actually a significant effort by us. There are very few companies right now in the United States that do multi-center gene therapy trials, and we do it. To do this we are essentially now entreating patients who have advanced glioblastoma, a brain tumor. This is a lethal moment in this person's disease narrative, and we are instilling into that brain tumor the weaponized adenovirus for the on-off delivery of IL-12 and you'll see this data submitted in just a few weeks now to the Society of Neuro-Oncology.

On the bottom of this slide is the sister trial where we're taking people who have advanced breast cancer, received the standard of care. Unfortunately, their disease has not gone into remission. They're in mortal danger, and they are also getting adenovirus for the purposes of generating an immune response with respect to a controllable IL-12.

Switching gears, to the ex vivo or the out-of-body generation of cells. As I alluded to, you need multiple shots on goal if you're really going to apply consistent pressure to oncology. So we are developing three broad portfolios. So this is different from many other companies.

The first is CAR modified T-cells. These T-cells are an engaged tumor with an immunoreceptor that is a handshake between the T-cell and the external surface of a tumor cell. When that handshake occurs it is not a friendly handshake between me and Sam, but it's a death grip, and when that death grip happens, those T-cells execute that cell that it's engaged with.

But in addition we are developing T-cells that sense the intra-cellular space. What's going on in that tumor microenvironment, in those tumor cells, beyond what you can see just on the surface? This, again, a very important point for ZIOPHARM and worth taking home, is that this then allows us to address a catalogue, a much broader portfolio of antigens, than is in the CAR space. So, again, I think is an important differentiator for us.

Then, the third is that, what happens if you don't know the tumor antigen? For this we are developing NK cells. And now you can see on the right hand side that we are in a position as a company and partnership with Intrexon to go after whether it be neo-antigens that are personalized for a patient, lineage specific antigens, the chestnut is CD19, or many B-cell malignancies, aberrantly expressed antigens, or when you have no antigen identified. All three of these are within our arsenal.

So we already have clinical data. These work stems from my work when I was at MD Anderson just a few short months ago in May of this year. Now we finished these clinical trials we will report on this officially at ASH in December of this year, but I will just share with you a couple of, I think, exciting points:

The first is that we can generate T-cells from patients and return them to patients. When we do so, especially in the context of non-Hodgkins lymphoma, and these are patients who have self-identified now to have very advanced disease. They are going to need transplant level conditioning therapy. We've followed these patients now for two years, and 86% of these patients now are in remission. We have also now infused T-cells that come from a third party. This is a match sibling or a family member. When those cells are weaponized to have that chimeric antigen receptor they are infused, and in this situation, about 60% of patients with ALL now have long-term remission, and interestingly, this is kind of a nuance to the field that we get at ASH, three-quarters of the patients who have had a haplo transplant are also in remission.

Portfolio of Next-generation Cell Therapies

So, as a company and as a leader in the field, it's insufficient to stop and say, ok, we are just going to have CAR modified T-cells or TCR modified T-cells. We have to dig deeper, and this is really enabled now with the Intrexon eco-system.

The first is that we are using their technology and essentially their speed to develop many CAR designs, but importantly a CAR, when it activates a signal - when it activates a T-cell, has an insufficient signal. A T-cell needs a complex repertoire of signals to be fully activated -- to kill and re-kill, to proliferate, to survive in that tumor microenvironment. It needs an additional signaling with cytokines. We understand that. For instance, the cytokines of IL-12, which we talked about, a cytokine called IL-15, and we are generating therefore libraries of molecules to put into T-cells for targeting and to recycle the target. And as I thought I alluded to, we've also had a leadership position around off-the-shelf T-cells, as the next slide will show this. We'll talk about that.

For the TCR modified T cells, those T-cells that can look at that the intra-cellular space for this, we really want to personalize the immunotherapy, particularly going after neo-antigens. Look for this program as in the coming months because we are going to be talking more and more about this.

And then the last is around NK cells and the type of biology we are doing around that so when we don't know the antigen.

Here's the slide that exposes you to off-the-shelf T-cells. Cells that can be made in advance of a patient's needs and infused when a patient requires it, rather than when the T-cells are available. For this we are using a genetic editing approach coupled with our ability to insert the chimeric antigen receptor, and that way you have a shot on goal that doesn't trespass and injure the patient such as where the T-cell receptor, which has now been eliminated, so it can't essentially damage the patient. But we are going beyond that, because we understand essentially the complicated nature between marrying one person's immune response and putting it into a recipient.

And since you'll be able to do that is an understanding of the HLA genetics and we have technology now where we are modifying the HLA molecules so that we can have sustained engraftment of these third party cells.

Strong Collaborations to Bring Therapeutics to Market

So here are the last few summary slides which really paint the picture that ZIOPHARM really is in an enviable position, because not only do we collaborate with the number one cancer center in the United States, MD Anderson, and it really allows now us to generate clinical data in an expeditious manner, but with the Intrexon community, we can target oncology and I didn't have a chance to talk to you about GvH, but we can talk to you about that in a Q&A session, where we can generate therapeutics for controlling toxicity of transplant, and then, of course, we have outlets through the NCI and through also with Merck and also enabled with the Intrexon flagship.

So when I think about Intrexon and I think about ZIOPHARM, I think about Intrexon as this engine, as this unrelenting drumbeat, this heartbeat, that allows molecules and DNA to be generated and then for ZIOPHARM to be the implementation engine. Then to feed back into the Intrexon ecosystem so we can learn about what we are doing and to develop an efficient process. And this allows us, therefore, to have a pipeline of activity. Which really, I think, is second to none.

Look on the top, we are in the viral therapy. We are a-l-r-e-a-d-y in the clinic, and we have therapeutic optimism about what our data are for glioma and breast. We are actively thinking about expanding indications and also of course to combine, because you need multiple pressure points if you are really going to target a tumor effectively.

On the bottom is the adoptive cell therapy program. We are already targeting CD19 malignancies. In the new year, we will be talking myeloid malignancies. We will be increasingly working on CARS and CARS & cytokines, targeting solid tumors especially as we start to bring the neo-antigen program into focus. And then the off-the-shelf, of course, because underlying all of this is the ability to get products into patients and to do it at low cost, because if the cost structure is excessive it will remain a boutique. So, part of what we do, is not only do excellent science, but keep our eye on the fundamentals so that this biology will be available to many.

Thank you so much.

DISCLAIMER: All postings made here are strictly for my personal record keeping and in no way, shape or form, am I even remotely suggesting others to follow my Buy and Sell moves. Trading options is definitely not for the faint of heart as one's portfolio can move up, or down, anywhere between 10%-30% during a single trading day. Feel free to follow my progress here, but PLEASE do not follow my moves. However, if, in spite of all my exhortations, should you decide to do so, be advised that you, and ONLY YOU will be responsible for any losses that you may suffer...In other words, the onus is strictly on you. On the other hand, if the move(s) result in a profit for you, I am open to discussing a split. ;)

Disclosure: I am/we are long XON, ZIOP.