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Talking Biotech is a weekly podcast that uncovers the stories, ideas and research of people at the frontier of biology and engineering.
Each episode explores how science and technology will transform agriculture, protect the environment, and feed 10 billion people by 2050.
Interviews are led by Dr. Kevin Folta, a professor of molecular biology and genomics.
Kevin Folta (00:00:01)
Hi, everybody, and welcome to this week's Talking Biotech Podcast. Now, over the last 11 years, we've seen a rise of new ways of reprogramming cells to help them take on new roles in cancer and taking on cancer cells, ⁓ or maybe even just ⁓ activating immune responses that drive the attack on cancer cells. And today we're discussing one of the most exciting frontiers in immunooncology. This is the story of oncolytic viruses.
We usually associate viruses with causing disease, but in this case, we're actually engineering viruses ⁓ to design them to selectively infect and destroy malignant cells while leaving healthy tissue untouched. Even better, when these cells within these viruses cause the destruction of cells, ⁓ it alerts the let me say that again. Okay, go back and fix.
Even better, when the viral destruction of these cancer cells ⁓ happens, it then alerts the patient's own immune system to hunt down the remaining cancer cells. ⁓ So the new technologies have modified and optimized the oncolytics virus to make it more effective in the systemic seek and destroy process. And it brings new tools to complement an existing toolbox against cancer. ⁓ So today we're speaking with Dr. Eric.
Poma. He's the CEO and director of Kaleidi Therapeutics. So welcome to the podcast, Dr. Poma.
Eric Poma (00:01:35)
It's a pleasure to be here.
Kevin Folta (00:01:37)
Yeah, so tell me more about oncolytic viruses. This is something I haven't really delved into over the years, and how have they been proposed to work as specific tools against cancer cells and not host cells?
Eric Poma (00:01:50)
Yeah, so great question. So again, in in oncology we're always looking for new mechanisms of action, new ways to destroy the tumor cell, and that's because tumors are great at becoming ⁓ at becoming resistant to other therapies. So there's always a rush in oncology to say, ⁓ can you come up with a new way of killing a tumor cell? So ⁓ there was chemotherapy, there was monoclonal antibodies, there was small molecules, there was CARTEs, there was ⁓ IO agents. Oncoloic viruses have always been fascinating to people from that perspective. ⁓
An oncolytic virus is just a virus that can replicate inside a tumor cell, and by replicating it lyses the tumor. So it's a very different mechanism of action. You're not ⁓ targeting DNA destruction, you're not blocking protein production, you're just replicating inside the cell and destroying it. So ⁓ people have always looked at oncolytic viruses as a really new way of ⁓ being able to attack cancer cells. ⁓ There's also a nice effect where ⁓ as the oncolytic virus replicates, it does trigger an immune response.
Your immune system, as you mentioned, we think about viruses as disease. Your immune system is very good at tracking where viruses are. So if you have a virus replicating within the tumor, ⁓ you can draw an immune response to the tumor, which is helpful. ⁓ And then finally, viruses are just packets of genetic information that express proteins. ⁓ And we can manipulate oncolytic viruses to express additional proteins while they're replicating inside the tumor cell ⁓ so that they can ⁓ have additional functionality against the tumor.
And the point about how do you design an oncolytic virus that only replicates in tumor cells, that is a blot of genetic engineering. I think we're on the forefront of that, and that's been a huge part of the field. ⁓ So that's been really exciting to kind of see that come.
Kevin Folta (00:03:33)
as I mentioned in the intro, but when you contrast this against other modalities, other types, things like car T's and things like that, why is the systemic nature of the oncolytic virus ⁓ a really good candidate?
Eric Poma (00:03:45)
Yeah, so so ⁓ where onkytic viruses have struggled is right now there's there's lots of evidence that if you directly inject an onkylic virus into a tumor, it'll replicate, it'll cause all these effects and you can get really good benefit, even in a patient who hasn't really responded to other things. We just saw that with replomes approval, with CG oncology, with ⁓ TVEX. So we were trying to have a like a nice data set here that if you can get the virus into the tumor, ⁓ that's great.
The problem with intratumoral injection is that most patients who have metastatic disease, you know, late-stage cancer, are not amenable to intratumoral injection. They have tumors throughout their body. ⁓ It's too dangerous to try and inject each tumor with a virus. So you have these problems with ⁓ intratumoral. ⁓ The holy grail has been systemic. This is how we deliver most drugs. For CAR T, you're not injecting it into the tumor, you're injecting it into the bloodstream, and it's going and finding the tumor. ⁓ The problem with oncolytic viruses is
When you inject them in the bloodstream, and again, this goes back to what you said in the beginning, your immune system does not know this is a therapeutic. Your immune system is highly evolved and very good at eliminating viruses in the bloodstream because ⁓ 99.9% of the time they're not supposed to be there, right? ⁓ So your immune system's really good at doing that. ⁓ It means that when you try to deliver oncolytic viruses, systemically they get cleared ⁓ by the immune system.
That's been the holy grail though. How do you deliver something that doesn't get cleared so that it can go to all these metastatic sites and have all these wonderful properties that we know oncolytic viruses can do once they're at the tumor? ⁓ That's the problem we've been working on for the past ten years and we think we have a really interesting solution.
Kevin Folta (00:05:22)
Yeah, let's talk about that solution. So how how do these viruses survive clearance? It seems like, you know, that the immune system and neutralizing antibodies, that's gonna be a real problem with any kind of therapeutic activity. So how do you do it?
Eric Poma (00:05:35)
Yeah, so the our our ⁓ next generation kind of scaffold here, we call it red tail. ⁓ We've done a couple of things that that are really interesting. We work off of a heavily modified vaccinia virus, and vaccinia has all these properties in and of itself that make it a really good place to start. ⁓ First and foremost, it's highly attracted to tumor cells, so it seeks out tumor cells because it's a great environment for vaccinia to replicate in. We've made a series of mutations to that vaccinia virus so that it can
only replicate in tumor cells though. So that's the specificity piece, right? It only replicates in tumor cells. And then I mentioned that if you have an oncolytic virus, you usually want to add some genetic payloads. ⁓ And Vaccinia virus is excellent at it's really flexible for adding genetic payloads and it expresses the payloads at really high level. So that was why we chose Vaccinia to start with. ⁓ It's tropic to tumor cells. ⁓ We were able to modify it so that it would only replicate in in ⁓ tumor cells ⁓ and it's really good at delivering a payload while it's replicating.
And again, if you have a if you're going to give something systemically, you want to make sure it's only going to replicate in the tumor cell. So that was a really nice ⁓ aspect of vaccinium. ⁓ To make it systemic, we did a couple things. ⁓ We know that in a normal infection with vaccinia virus, ⁓ 99.9% of the virus lacks what we call an outer membrane or an envelope. It's highly aminogenic, the immune system clears it really well. In fact, it's the basis for the smallpox vaccine. We call this the IMV form.
We selected for and engineered for and have kind of developed a manufacturing process for that 0.01% of the virus that takes on the envelope of whatever cell you grow it in. ⁓ And by taking on that membrane, that envelope, it's heavily shielded from the immune system. I sometimes give the analogy that if ⁓ you robbed a bank and as you leave, you put on a policeman's uniform, there's a much higher chance you're gonna get out. You look like you're supposed to be there, right? And that's what the envelope does for a vaccine.
So that was step one, and we've seen in all of our ⁓ animal models and all of our ex vivo human studies that ⁓ that envelope really helps avoid immune clearance. It's harder for the immune system to recognize that this is foreign because it's covered in a membrane from a normal cell. ⁓ The other thing we do though is we also genetically engineered the virus to express high levels of a protein called CD55. ⁓ So CD55 is just a protein that a lot of normal cells have that tells the immune system basically to stay away.
Eric Poma (00:08:00)
So just don't you just kind of move along, nothing to see here. ⁓ So we for the first time have created this form of vaccinia virus that has the envelope ⁓ and has high levels of CD55 expression. ⁓ And from everything we see in our animal studies, whenever we expose this ex vivo to human samples, ⁓ blood samples, complement factor, all that kind of stuff, ⁓ highly, highly protected from immune clearance. ⁓ So this is just, you know, ⁓ a decade plus of genetic engineering work and
carefully kind of looking at biology to kind of come up with ⁓ a way to do this. And now we're very, very excited.
Kevin Folta (00:08:37)
I guess that that's really a useful way to think about the shielding. So you're covering with a membrane, plus you're expressing a protein ⁓ which ⁓ says nothing to see here. ⁓ But what is it that targets a oncolytic virus specifically to a tumor cell? How does it do that? And then ⁓ yeah, let's start there and then we'll talk about payloads.
Eric Poma (00:08:46)
Yeah.
Eric Poma (00:08:52)
Yeah.
Eric Poma (00:08:55)
Yeah, so there's there's different ways of doing that. ⁓ with some of the other viruses that people have used in the past, like adenovirus, ⁓ the tumor has to express a certain receptor. If it doesn't express that receptor, it's not going to get there. And so you can also imagine that ⁓ if you're attacking the tumor via a certain receptor, ⁓ the tumor will mutate and get rid of that receptor. And so now the virus can no longer get there. The thing I mentioned about vaccinia that's interesting is that vaccinia seeks out
environments where the cells are growing rapidly, so there's a lot of metabolic activity and a lot of material for it to replicate. ⁓ So for reasons we don't fully understand but have been well documented in the field, it's highly attracted to tumor cells. So ⁓ now we use this virus that again we've modified it so that it can only replicate in tumor cells, but the minute you put it into the bloodstream, we've seen this in all of our animal studies, it ignores all the other organs that goes straight to the tumor, right? And that's where it replicates. And so
That's that was one of the reasons we chose Vaccinia because it seeks out ⁓ environments like what a tumor cell has where they can replicate really efficiently.
Kevin Folta (00:10:02)
Well you mentioned the idea of payload, ⁓ but if this thing is just by its own nature oncolytic, it's finding tumor cells going inside via some sort of receptor mediated transport. ⁓ Then ⁓ it replicates and then that's typical lytic cycle of a b of a virus. So what are you adding as a payload that makes this work especially better?
Eric Poma (00:10:24)
Yeah, and again again, I think in oncology, one of the things we've learned over the last seventy years is if you have something that works, try and combine it with something else that works and works differently. Because again, tumors are very good at coming up with resistance mechanisms. It's harder, it's harder to dodge two or three punches than it is to dodge one, right? And so what we've done here is we said, look, we have a way of just lysing the tumor cells. The virus bits of the virus that are there are drawing an immune response to begin with, but that immune response tends to be transient.
Because the immune system comes in, clears the virus, and leaves. So we've added a payload here called Ile-15 superagonist. And what that is, is a very, very potent stimulator of NK cells ⁓ and a subset of ⁓ CD8T cells that are really extraordinarily good at destroying tumor cells. So now again, you're lysing the tumor, it's drawing in an immune response, but then you're having all this IL-15 superagonist just at the tumor, just in the tumor microenvironment.
And that is putting a match to ⁓ the immune system to come in and try to clear out the rest of the tumor. ⁓ And so what we've seen when we look in animal models here is that ⁓ if you have the virus alone that doesn't express IL-15, you have a really nice benefit in terms of reducing tumor size and all that. But if you add the IL-15 expression piece to the virus, we're seeing really great tumor clearance, much, much better than just one mechanism alone. And so again, this is standard dogma in oncology.
If you can if you can have multiple mechanisms of action, there's much less of a chance for the immune s for the tumor to to ⁓ become resistant. And we're seeing that here. The difference is this is a combination of mechanisms of actions, but it's
Kevin Folta (00:12:06)
And maybe taking a step back, ⁓ just in our conversation, and kind of think about this, it kind of came to mind. When we're talking about an oncolytic virus, why do these exist? I mean, are they are they viruses that are just typically kind of latent and present in our in our bodies or in our environment ⁓ that have a higher affinity for tumor cells because they exploit the ⁓ higher replication or less ⁓ you know ⁓ inhibitory cycle with respect to replication? ⁓
that that is what drives them and that they just perform better in that environment? Or you know, what's the story on these things?
Eric Poma (00:12:41)
The the Yeah, that's exactly right. I mean there are there are obviously thousands and thousands of different kinds of viruses out there. Each of them has their own each type of virus has their own kind of ⁓ specific niche where they like to replicate. Some replicate really slowly, some are latent, but some are replicating rapidly and looking for an environment that allows them to replicate really quickly. Again, a virus is not a living thing. It requires a living thing to be able to replicate.
And so over the years, we've identified a set of viruses that replicate really nicely in tumor cells. That was kind of the building block. That was kind of where we were 20 years ago in the field. Now we've kind of said, okay, the problem is that some of these viruses replicate really nicely in tumor cells, but they also replicate in some normal cells. And so that's where genetic engineering has come in. And again, for our form of vaccinia virus, we've been able to get rid of some of the genes that allow it to replicate in a normal cell.
But those genes are compensated for in a tumor cell. So the virus can replicate really nicely in a tumor cell. So you start with what nature provides, but then you kind of bring the engineering in to kind of get to exactly.
Kevin Folta (00:13:52)
Now this is really neat. We've been talking a lot about different strategies over the last few months and ways of mitigating issues like cancers and attacking different ⁓ different types of cancers. We're speaking with Dr. Eric Poma. He's the CEO and director of Khalidi Biotherapeutics, ⁓ and we'll be back in just a moment. ⁓ And then we take a break here. We're about halfway. ⁓ from here, I got a few more questions. We'll go for then and then anything you think I should ask. But here we go. ⁓
⁓ I gotta give a few seconds of blank here.
Kevin Folta (00:14:30)
It helps the producer with some leave some blank space and clear out the background. Okay, here we go. And now we're back on the Talking Biotech podcast. We're speaking with Dr. Eric Poma. He's the CEO and director of Khalid Biotherapeutics. And we're talking about oncolytic viruses ⁓ and families of viruses which have now been genetically engineered to specifically seek and destroy tumors ⁓ and also stimulate the immune system.
Eric Poma (00:14:33)
editing and stuff. ⁓ Nice.
Kevin Folta (00:14:56)
To attract them to what's left over after the lysis is over. ⁓ And on the front side of the ⁓ break, we were talking about how these perform and why some of the advantages of these viruses. ⁓ Where is the work currently being done? Is this all preclinical right now and animal models? And and what are some of the ⁓ types of tumors that have been ⁓ corrected?
Eric Poma (00:15:20)
Yeah, so so we've been looking at ⁓ both in vitro, so cell cell-based work, but we do a lot of in vivo animal-based work ⁓ and ex vivo work. And so the in the animal-based work that we do, we're always using mice that have a normal immune system, because again, the whole challenge is can you overcome that immune system? ⁓ And we've looked at mice that have breast cancer or lung cancer, a host of different bladder cancer, like a host of different tumor types, and we've seen that effect consistently. ⁓ The other thing we do is we take
Immune cells from a patient or a donor and we put them on ⁓ you know a a dish with the virus and we see if that immune system can inactivate the virus. Again, trying to see if if this will survive ⁓ clearance by a human immune system. ⁓ So both those kind of aspects of work have have been really ⁓ great here. We've seen really nice results. ⁓ We had a discussion a few months ago with the FDA about starting clinical studies. We kind of showed them all the data, showed them our plan forward, they they agreed with the plan, and so now we're looking at
Starting our first studies in humans ⁓ first quarter of next year. So we're kind of barreling towards the clinic. There's a lot of work that has to be done there ⁓ from a manufacturing standpoint, showing that you have ⁓ consistency and stability in your manufacturing process. That's just very important here. ⁓ But we feel like we've kind of shown scientifically as much as we can with the models that are available that ⁓ virus avoids the immune system, hones into the tumor.
replicates in the tumor, destroys the tumor that way, and also expresses IL fifteen and fundamentally changes the tumor microenvironment. Apologies.
Kevin Folta (00:16:51)
Yeah, what's particularly exciting about this is that you we keep saying tumor rather than thinking about blood cancers, which are sometimes more amenable to some of these therapies because of their availability. Here you're looking at a solid tumor based approach. ⁓ And is there some type of tumor that would be more amenable to this than others, like different types of ⁓ histology that make more sense?
Eric Poma (00:17:12)
Yeah. Yeah, I mean I your distinction between between hematologic and solid is a really good one. And again, the problem with solid tumors has been that ⁓ as you say with a hematological tumor, the CAR Ts can go everywhere and destroy those cells, and there's no tumor microenvironment that excludes immune cells. Whereas solid tumor, that's the case. We know that the tumor microenvironment keeps immune cells out, very hard for them to get into the tumor microenvironment and help clear the tumor. ⁓ So ⁓
Here we've been looking at tumor types that we know like non-small cell lung, melanoma, ⁓ renal cancer, head and neck cancer. These are tumor types that ⁓ patients initially do well with immunotherapy. So they get a PD1 inhibitor, and that can really help get T cells activated against the tumor, ⁓ but over time the tumor becomes resistant. And we know the resistance mechanism usually has to do with ⁓ shedding of HLA, inhibition of of antigen presentation.
So we think that's a perfect place to go in with an oncolytic virus that breaks open the tumor cells, and then IL-15 that draws in NK cells, ⁓ gamma delta T cells, NKT cells, T cells and NK cells that work differently than traditional CD8s that are activated by ⁓ PD1. So we think this is a perfect setting to have these two kinds of mechanisms of action at play. ⁓ These are patients who have no other option therapeutically.
But the way this drug works, we think we'll be able to recalibrate their immune system ⁓ to attack the tumor as we're destroying the tumor via the virus itself. So very excited about that. It's a large patient population when you talk about non-spal cell lung, head and neck, ⁓ melanoma, those are some of the biggest tumor types in the world. ⁓ But we think these are the right tumor types ⁓ for this mechanism.
Kevin Folta (00:18:56)
What's also interesting that comes to mind is that once you've done this, haven't you trained the immune system to let me think about this for a second. Yeah, what haven't you trained it or to permanently ⁓ seek this type of tumor type?
Eric Poma (00:19:05)
No.
Eric Poma (00:19:10)
So th that's a that's a great point. And this is if you if you think about the first set of data that came out with PD1 inhibitors, this was a new way to kill cancer cells. You were getting CD8s to kill the cell instead of using chemo to kill the cell. And if in the beginning there was a debate about, well, does it really matter which way you kill the cancer cell? You're still killing the cell. But what we've seen with PD1 inhibitors and CTLA4 agents is that you have this long tail where some patients go into a response.
That is extraordinarily deep and extraordinarily long lived because their immune system now can recognize tumors in different locations and clear them as well, long after you stop giving drug. ⁓ So here we think the same thing may happen. As you get gamma delta T cells engaged, as you get NK cells engaged, ⁓ you may be triggering a memory immune response to the tumor ⁓ that can allow for clearance of microcytes that you didn't get to, that you weren't able to get to, that can give this long term.
remission. So yeah, we think that, you know, the fields learn, mechanism matters, ⁓ IO ⁓ in some patients can really make a dramatic difference. And so here we're we're really excited to try and add to the the breadth of what you can
Kevin Folta (00:20:21)
And kind of going back to the virus, you you mentioned th ⁓ this particular virus is particularly useful for design of ⁓ constructs which can have effect. And so what are some of the design limits that you have here that ⁓ may make it particularly useful for complementing other types of approaches?
Eric Poma (00:20:36)
So yeah.
Eric Poma (00:20:41)
Yeah, so we're we're ⁓ we haven't pushed up against the limits yet. We found that we can put multiple payloads. So, you know, we we designed this virus that shielded from the immune system, hones in on tumors, only replicates in tumors. The first molecule we're moving or the first virus we're moving into the clinic expresses IL fifteen superagonists. But we're seeing that we can put two or three payloads in and have multiple things being expressed. Again, cancer is extraordinarily complex.
You want multiple mechanisms of action here. And so we're we're still kind of testing the limits. How many payloads can we put in? And we've been seeing two works great, three works great. So we're still kind of pushing at that, but it's hugely exciting because ⁓ it's not just one drug. This is an entire platform where you can really kind of design some bespoke viruses here that express payloads tailored to the kind of tumor microenvironment.
Kevin Folta (00:21:35)
Yeah, I'm a big big fan of CAR T cell therapies, and I think they're so cool and I teach about them and talk about them in my classes, ⁓ but the cost of doing it and the technical barriers are huge. ⁓ And so when you contrast that against something like oncolytic viruses, how much of an advantage does the oncolytic virus have?
Eric Poma (00:21:54)
Yeah, so the the nice thing here is cost of goods is very similar to like a monoclonal antibody. So very, you know, v you know, an order or so a magnitude lower than a CAR T. You also have the potential for repeat administration, which is difficult for CARTs. CAR T's are usually, you you do the conditioning therapy, you get your treatment, and then that's it, right? Like it's very hard to come back for a second round. Here there's the potential to do multiple doses. And it's just ⁓ again, CAR Ts are a hugely important aspect, but they've been limited to hematologic.
And that's because of how difficult the tumor microenvironment of the tumor is for T cells to penetrate. ⁓ We think when you have an agent like this that's in there that's destroying tumor cells but also expressing IL-15 superagonus, which pulls in immune cells. ⁓ And you can express other payloads to help break down the TME and pull in more immune cells. ⁓ We think that can be really transformative on its own. We think that that can open doors to combination with CAR T and things like that. This idea that you have to dismantle.
the tumor microenvironment, I think, is really catching on with people. ⁓ And one way of doing that is by introducing at high concentrations the cytokines that change the tumor microenvironment, but only in the TME, because you can't express them throughout the body or you'll get huge immune reactions. ⁓ So this is again super exciting to us. We're really we we really think this is a a differentiated strategy.
Kevin Folta (00:23:13)
Yeah, that that opens up all kinds of possibilities. Cause if you can destroy that microenvironment and really open that up, you now have availability to many other types of therapy, like checkpoint inhibitors, standard chemotherapy, even probably much better. So are those ⁓ synergistic combinations that might be explored down the road or are being looked at now?
Eric Poma (00:23:32)
Yeah, we we we plan on starting the phase one, as I said, in patients who have exhausted all treatment opportunities. We're gonna do this as monotherapy because we think the drug alone is gonna have profound effects. But most drugs that get approved in oncology start as monotherapy in late line and then if they're successful, they're moved earlier by combination. If they have a reasonable side effect profile, if they have a differentiated mechanism of action. ⁓ So we think that's strategy will hold here as well. Show that the drug is safe and active on its own.
And then start combining it with ⁓ medications that make sense like a PD one inhibitor early.
Kevin Folta (00:24:08)
And so ⁓ when you compare this against other targeted therapies like ⁓ targeted lipid nanoparticles or the antibody drug conjugates, ⁓ how does this really compete? I mean, is it is it s ⁓ similar, same, I or l different? Maybe what are the advantages or disadvantages?
Eric Poma (00:24:22)
Yeah, so so ⁓ yeah, the antibody drug conjugates ⁓ are are great. ⁓ I think what they're doing is trying to replace chemotherapy, right? 'Ca th their payload is usually chemotherapeutic. And the idea with the antibody drug conjugates is right now when you give someone chemo, it goes everywhere. So you get ⁓ hepatic tox, you get renal tox, you get nausea, vomit, you get all that kind of stuff. ⁓ If you can just specifically target the chemo to the tumor, you should reduce the burden of toxicity.
But you're not adding a whole lot of efficacy, right? It's just you're just getting rid of toxicity, which is hugely important. ⁓ So here we're doing something different. It's a very different mechanism of action that involves tumor lysis and bringing in the immune system. So you could see combination with those. ⁓ The lipid nanoparticles are closer to what we're doing in the sense that you're usually trying to bring in a payload, and it can be a genetic payload, DNA or RNA, and all
those are are interesting approaches. They're usually non-replicating, so it's a kind of a you don't have a huge effect for a long period of time, whereas the virus is in there replicating and putting out payload at high levels for weeks at a time. ⁓ So those are more ⁓ potentially competitive ⁓ if if you really are trying to use ⁓ nanoparticles to deliver genetic information, but we think there's inherent advantages to the virus in that setting.
Kevin Folta (00:25:44)
And is there ⁓ you mentioned head and neck and small cell lung cancers before, ⁓ but are there particular tumor types that are a little bit more amenable to the viral therapy than others?
Eric Poma (00:25:55)
Yeah, I I think it's those. We've seen that the virus is great at lysing just about any solid tumor. ⁓ But again, ⁓ you know, would we have activity in pancreatic cancer? We might, but pancreatic cancer never responds to the IO mechanism, right? It doesn't respond to immunotherapy. So ⁓ we've been focused on saying, let's go into a disease where there'll be the oncolytic virus effect ⁓ and where the IL-15 superagnes is likely to have a huge effect as well. So that's ⁓ lung cancer and head and neck and melanoma.
renal cancer and and you know those kind of areas because we we kind of want that one-two punch. ⁓ Will we explore something like pancreatic or colorectal down the road? Yes, but for the beginning we want to see what it you know what is the best shot here and it's probably a disease like non-small cell line.
Kevin Folta (00:26:42)
What does the road look like for this? I mean I I'm very ignorant to like the timing and the pipeline to this, but you right now you're pre clinical. ⁓ How ⁓ what happens next and about when might this kind of thing find the light of day if everything goes really well?
Eric Poma (00:26:58)
Yeah, so ⁓ we hope to dose the first patient first quarter of next year. ⁓ And you know, phase one studies are dose escalation, so you're looking for the right dose, you're looking to make sure the drug is safe, and then you're hoping to see efficacy. Here we've tried to push everything towards making this an efficacy study. There's only four doses we're gonna test. We're quite certain the drug is safe, or everything we we've seen suggests that th this kind of approach is safe.
And what's exciting here is if you dose a couple of patients, say you dose three or four non-small cell lung cancer patients, ⁓ and one or two of them, you're seeing their metastatic sites resolve, you're seeing them go into a response. ⁓ It's certainly not enough to approve the drug, right? There's still all these questions about. ⁓ But what's interesting to us is that would be enough to say, well, I think they designed a drug that can be delivered systemically. It's not getting cleared by the immune system. It's showing up at the tumor and these distal sites and it's having its effect. So ⁓ this is one of those cases where
You're gonna have to wait the standard, you know, anywhere from four to eight years to get a drug approved. ⁓ But you may know, you know, six months into the phase one whether or not our our platform is working. And so there's a huge step up in valuation if the platform is working, right? And so that's what's exciting.
Kevin Folta (00:28:12)
Yeah, that's all very exciting. I think that the s you know, just kind of an interesting point that I heard somewhere a while ago. Are there veterinary applications that can kind of ease into that ⁓ f you know, ⁓ traditional phase one, phase two, phase three human trials where you really can learn a lot about what happens from the veterinarian or agricultural animal ac application.
Eric Poma (00:28:31)
Yeah.
Yeah, I mean it's a it's a good question. It's one we've kind of looked at. I think we're gonna go straight to human here, but we we were curious about some of the canine models ⁓ that that they have. Well you know, canines unfortunately get a lot of sarcoma and get some other cancers as well. it's an interesting model, but we felt like it would actually be faster to go straight into patients, so that's what we're kind of geared up for. But yes, it's been f it's been fascinating to see those models kind of evolve.
Kevin Folta (00:28:59)
Yeah, it's been kind of interesting to see how that has been ⁓ some companies have just said we're just gonna do this in veterinary and make it strictly a and then maybe transition over to humans just because of the time lag that's there and and the proof of concept. Plus dogs seem to go faster than than humans do, but you ⁓ know, very interesting stuff. So is there anything else that's in the pipeline over at ⁓ at at your company that ⁓ would be particularly exciting or maybe extensions of this work?
Eric Poma (00:29:11)
Yeah, exactly.
Eric Poma (00:29:15)
Yeah, yeah, yeah.
Eric Poma (00:29:27)
Yeah, it's it's extensions of what we talked about. The the first compound gets in, destroys tumor cells, expresses IL fifteen superagnes. We've been working on some compounds that we're really excited about. That they they s survive systemic administration, they get to the tumor, they express IL fifteen superagonus to activate the immune system, ⁓ but they also express high levels of ⁓ bi specific antibodies, right? So that you have high levels of biospecific antibodies and a tumor microenvironment that's more permissive now. ⁓ So stuff like that, just you know.
picking in and putting in different payloads to really try and get to the biology of the tumor microenvironment.
Kevin Folta (00:30:01)
Yeah, are there non cancer applications of ⁓ of ⁓ oncolytic viruses?
Eric Poma (00:30:06)
Yeah, I mean if if you know the history of oncology, a lot of drugs that start in oncology end up in autoimmune disease. And ⁓ we've been looking at that potential as well. Is there a way to target B and T cells here for not only destruction, but also to express at high levels ⁓ an immunosuppressive agent where the site of inflammation is? That's further along, that that's further down the road for us, but I think it's a really interesting area. And certainly again, there's lots of history of agents going back and forth.
Oncology and ⁓ immunologists, you know, people are looking at CAR T pretty heavily and ⁓ autoimmune disease these days.
Kevin Folta (00:30:43)
Very good. all right, Jim, I'm gonna put an put a ⁓ quick note in here to edit this part out. This is at 3049. So is there anything else I should ask you that that we covered?
Eric Poma (00:30:54)
No, this was great. This was really comprehensive. I appreciate how much homework you did on this.
Kevin Folta (00:30:57)
Well, it's it's it's it's turning into a hobby with thinking about n interesting cancer modalities. It's you know I'm a plant biologist. I don't you know, so ⁓ the only tumors we deal with are agroacterium. ⁓ okay, well that ⁓ no, very good. it's fun stuff here. I'm gonna write down a note for somebody. Okay. ⁓ so I'll just ⁓ thank you then in just a second here and then we'll go from there. Just stay with me till we get totally uploaded, but here we go.
Eric Poma (00:31:10)
Yeah, right.
Kevin Folta (00:31:25)
Well, Dr. Eric Poma, thank you so much for joining me on this. I it really was an education to learn about these oncolytic viruses. It's kind of a really interesting area. ⁓ And please, please, please contact me again when things move forward and we'll talk about where things are at and ⁓ the progress going forward.
Eric Poma (00:31:44)
Thank you so much, it was a pleasure to be on and thank you.
Kevin Folta (00:31:47)
Yeah, and just another exciting way that we're taking on cancer cells using a different approach. And what makes this so exciting is that it's working on solid tumors because we've talked about all the neat therapies that are really bound by the physical problems that solid tumors present. ⁓ So this is a good opportunity to be able to attack that specific type of tumor using an oncolytic virus. This is the Talking Biotech podcast, and we'll talk to you again next week. And that is it. Stop.
Eric Poma (00:32:04)
That's right.