Peter Emtage, Ph.D. Vice President Immunology Intrexon

Peter Emtage, Ph.D.
Vice President
Immunology
Intrexon Corporation
Thank you very much Jack, welcome to everybody. It’s my job to take you through a little bit of what we do within the sector of health and what is applicable across a broad number of sectors. I’m going to leave that to the specific sector-heads
to talk about, I’ll be more centrally focused on health.
The important thing here to focus on in my talk is collaboration. Right? There’s two mutually beneficial parties, working
together to facilitate a downstream delivery, which is heralded by all of the technologies that Tom and the team just mentioned. That’s our focus. How we deliver is the metric which guides us to set that standard for all of our partners, and I’m
going to take you through a little bit about that.
I came to Intrexon about a year ago from Medimmune, where I led and drove the immunotherapy portfolio (PD-1, PD-L1,
OX40). Those are really exciting programs, but limited. And the only way that we in an oncology field can succeed is the
delivery of two harmonizing mechanisms and this is where this technology takes us. It builds a better paradigm for delivering to an individual with cancer, multiple mechanisms. So, where [other] companies focus on one anti-body, we focus on a
T-cell for instance and multiple levels of delivery. We can do, within that, using this technology, modify and manipulate to
our better benefit of patients with cancer. And I’m going to move away from the cancer, but I just wanted to tell you what
got me excited about coming to Intrexon.
So, Sam alluded to where we came from with our technology. This is just a brief example to show you where we were in
1998 and what’s sexy now in 2014-2015. Right? We’ve got the ability to modify, manipulate and leverage a database that
has componentry that allows us to do anything, really. Right? We can get context, we can get tissue-specific expression,
we can up-regulate, down-regulate from a genetic module point of view. And that’s really, really what it’s all about for our
partners, is leveraging that technology downstream into therapeutic benefits.
How do we do that? Well, we focus on a number of mechanisms. We focus on viral technologies, lentivirus, AAV,
Adenovirus. You’ll hear from my colleagues Suma and Lawrence Cooper who’s here from Ziopharm. We also look at nonviral delivery with a plethora of technologies to be able to bring into a therapeutic paradigm, a delivery modality (?) for our
core technology, which is DNA modules and leveraging that component on behalf of the ECC’s.
We also have the ability internally to modify any cell type that you can think of. So where you think about being able to
bring a specific therapeutic to the market, we’re thinking about how to harmonize it and then how to deliver it. And those
two things come together to give you the best benefit in DNA from a modular componentry.
You’ve heard the word RheoSwitch technology. So in addition to building stretches of DNA with multiple mechanisms and
multiple, or to up-regulate, down regulate the levels or protein expression for therapeutic modules, we can also place
in front of that cassette a small molecule ligand controllable mechanism. And again you’ll hear some of that today after
my talk. But this gives us the ability to leverage safety and activity with a small molecule switch. Right? So that’s really
cool. You know, we are constantly refining this technology and engineering around it to bring better componentry to our
partners.
In addition, you might have heard about AttSite recombinases. We have other technologies outside of RheoSwitch and
DNA platforms that really allow you to modify the genome of an individual, a cell, a plant, an animal; to really start to know,
build and define that best program or best direction forward.
This slide we threw in to just show you where we are with the RheoSwitch technology and it’s important because it really
is, at this point in time, a solution that a number of our partners have chosen to move forward with. But we believe it’s the
tip of the iceberg. As these systems become more and more refinable, they allow our partners greater and greater flexibility to build that solution which is tailor-made for their therapeutic. And that’s what it’s all about for us.
Outside of RheoSwitch, I wanted to just show you two additional things here, which you might not be aware of. For
instance, we are looking pretty heavily at micro-RNA’s. So, whereby with the technologies that Tom alluded to, where we
can set up a paradigm, we are now taking a step back and looking at how the cell does that; not to control the expression
of one gene sequence per se, but to control entire pathways.
So the biology around micro-RNA’s allows you to go in and regulate a pathway negatively or positively, but more importantly, globally. So we’re looking at mechanisms now to really bring that delivery mechanism and the platform or vehicle
in which it’s expressed in, more to the forefront of controllability. Which I think is very important, because it shows the
flexibility within the system and how dynamic the innovative engine is at Intrexon. So we’re harnessing these. Stay tuned.
More to come.
Outside of the DNA/RNA modality, we are also looking at modulating the biological effects of T-molecules. Some of them,
which I’ll mention here, maybe have, you know, a lot of safety in the clinic. And the question for us is, we don’t want to
ignore those because we believe, especially in an area like immune-oncology, we believe a lot of those molecules could
have substantial benefits to patients with cancer. Or auto-immunity. Or infection. But how do you harness that? So, stepping outside of the paradigm of DNA and mRNA, we’ve gone the extra distance now into protein modification and modelling. Right? And I want you to understand one thing. All that I’m talking about is not hypothetical. It’s done at Intrexon, with
Intrexon staff. Right? And it’s key that you know that that’s the innovative engine that drives our partner’s success.
So how do we do that? Right? We take a look at the protein, we make specific modifications. We take that modification
and we apply it and we ask the simple question: Can we modulate the toxicity of that very crucial molecule that we believe
will have an impact in a patient? And to a large extent, we can. And we are actively building that capability now to be able
to deliver to an individual such modalities as we move on with our development paradigm.
So how do we leverage this? Where do we leverage it? Right? Again the technologies are very versatile, we can just leverage it in multiple cell platforms. You know, I’ll tell you a little bit about our T-cell platform. Sumo, you know, will tell you a
little bit about other cell types we modify. You know, biological effectors. There is no limit here to what we can do. We can
take it from a cytokine molecule to a transcription factor to a small RNA. We can control it with the RheoSwitch, you know,
we can really get it to do what you want it to do. Right? If it’s got a tail and it’s furry and it smells and it barks, it’s a dog.
We have it. We can build this for you. Right? We can do that. We’ve got the mechanisms in place to control and we’re
constantly developing, from an innovative point of view. And at the end of the day, this is all heralded with one singular
function in mind. Right? To bring benefit to any patient, or any individual, or any system that we choose to, to deliver a
very finite solution to our ECC partners. And that’s what our job is.
So just more specifically, and I’m running out of time so I’ll be a little quicker. But I wanted to actually comment on, so you
get a feel for what we’re doing, especially in a space that has garnered a lot of interest these days, immuno-oncology. So
I’m an immunologist by training and I’ve been in this space for twenty years. I’ve looked at auto-immunity, cancer, infectious disease. The leveraging, the technologies and the cutting edge techniques that we’re using – we built out a group to
be able to deliver to our partners, Ziopharm and Merck KGaA Darmstadt, the best solutions to do that.
The team is pretty large, and it’s constantly expanding. We have biochemists, immunologists, protein biologists, protein
modelers, an entire health combined with Suma’s team. We have regulatory, manufacturing, we have all of the infrastructural pieces necessary to deliver a full solution to the clinic for our partners. Which is important. Because we take it from
the bench, we take it to the bedside and we hand it off. The knowledge framework is deep, right? We can pull flexibly on
any component that we need to, to deliver these solutions. And really, leveraging from the base aspect, which is DNA.
That’s what we do, and we do it well.
More specifically, to an example from an immune-oncology point of view. Lawrence will take you through a little bit of the
non-viral DNA delivery mechanisms and some of the strategies within Ziopharm. I wanted to show you that for our partners we harness everything. So in addition to looking at Sleeping Beauty systems, non-viral systems, we also at things
like lentiviral systems. And the example here is to show you that within the space of about ten months, we can go from
a lentiviral system to a CAR-positive T-Cell to a very highly active CAR to a CAR that treats mice. Right? And that might
come across as ‘mice,’ but I think it’s important to know that this technology, this approach, is going to translate into the
clinic. Right? And it keeps us competitive. So now for the first time we have a flexibility, which is viral and non-viral DNA
technologies for building the best clinical solutions for patients with cancer, for patients with auto-immunity, for patients
with orphan diseases.
And with what I wanted to end with here (thank you) is, you know, multiple companies play within this space. But when
you really and truly look at the offerings of Intrexon, it’s broad. It’s deep. It’s across the entire gambit. So whereas one
company focuses in one area, the total solutions that we can bring to partners is global, within this space.
Thank you very much.