transcript
Episode 2
AR Ventures Accelerator Program (Part 1): New Approach to Chemotherapy Using Liposomes
Joe Schaffner: Welcome to the BioVentures Podcast, where we discuss all things related to technology transfer, entrepreneurialism, research, intellectual property and innovation. My name is Joe Schaffner, outreach coordinator for BioVentures.
Stefanie Kennon-McGill: My name is Stefanie Kennon-McGill, the senior program manager at BioVentures. And today we are joined by Dr. Samir Jenkins, who is one of our ARHVA awardees. ARHVA is the AR Health Ventures Accelerator. It is a relatively new program that we started at BioVentures to fund and support commercialization of some of our more promising projects that we’ve got going on at UAMS. So ARHVA is different than your traditional funding mechanism. We do provide money for researchers to do their work, but we also try to provide input. We do the organizing and progress tracking for the inventors to try and take some of the burden off of their shoulders so they can just focus on doing the work. So Samir is in our first cohort of ARHVA awardees, and we’re really happy to have you here with us today. Welcome. Thank you. And so we want to learn more about your ARHVA work, what it is and what the goals are.
Samir Jenkins: So I work in the Department of Radiation Oncology, but I have a long background in nanoparticle-based drug delivery, and chemotherapeutics are typically limited by their toxicity in organs that are not tumors, and so what we’re trying to do is encapsulate chemotherapeutics and liposomes and then use ionizing radiation to release them specifically at the site of the disease, so that the drug doesn’t affect all of the other healthy tissue in the body, and because of the way that radiation treatment works, we can target a tumor very specifically.
Kennon-McGill: Can you explain what a liposome is?
Jenkins: A liposome is a ball of fat with water in it. It’s a lipid bilayer membrane with an aqueous, a water interior, and so you can load hydrophobic drugs into the membrane and hydrophilic drugs into the core. They’re about 100 nanometers across, which is meaninglessly small.
Kennon-McGill: Hence the nanotechnology term.
Jenkins: Yes. So there are several liposomes that are already actually in the clinic, but none of them use radiation as a trigger for release. They try to rely on something like an internal pH change, an external heat source, or time for the release. And this is trying to be a bit more precise and a bit more calibrated, how we’re releasing our drugs and where we’re releasing our drugs.
Schaffner: Can you describe the current status of the technology, including any successful tests or validations? Is the current state of the field what you’re trying to do?
Jenkins: So there’s not very much being done in other places, using radiation as a trigger. That’s one of the things that Arkansas happens to be really focused on. You guys can’t see it, but we just opened a big proton building behind us. Radiation is something that Arkansas always focused on. There was another company that came through BioVentures that had a similar technology, but their radiation triggered release was based on having a reactive cargo, whereas what I’m trying to do is build the trigger into the membrane itself. And so I’ve done a couple of tests loading cisplatin into it, and I’ve gotten a good release as a result of radiation, whereas it stays intact in the absence of radiation. And so we’re kind of at a point of trying to really optimize everything and get the recipe correct, and then we can move forward into the in vitro testing, the in vivo testing, which is much more – I’m a chemist by training, so biology stuff is very rote and cut and dry, right?
Schaffner: And so I’m liberal arts, so maybe continue go into cisplatin a little bit as far as what, what exactly is that?
Jenkins: Cisplatin is a dichloro diamino platinate.
Kennon-McGill: Did that help, Joe? [laughs]
Schaffner: Yes.
Jenkins: So it’s a planar molecule. It’s got a platinum ion in two-plus state with two chlorines and two ammonia groups attached to it as ligands. And the cyst part is important, because basically, if you were to take it and look at it, the ammonia are on the left side and the chlorines are on the right side – or whatever – they’re on the same side. It doesn’t matter which side they really are. And what happens is, as you put the system into the body, the body is also full of salt. Salt is sodium chloride, and so that keeps that in equilibrium. When it goes into tumor cells, those cells have a lower chlorine content than the outside. So the chlorines come off of the platinum, and they get replaced by water that then goes and gets displaced by components in DNA in the nucleus, and so that ends up putting in kind of a tire spike for the DNA polymerase, and it prevents replication.
Kennon-McGill: For cancer?
Jenkins: For cancer – well, preferentially for cancer. But then there’s off-target effects that, like in the kidney in particular, that limit the amount of cisplatin that you can actually get.
Kennon-McGill: So would your technology then allow for bigger doses of cisplatin?
Jenkins: In theory, yes, you should be able to either get larger doses of cisplatin, or at least more localized large doses of cisplatin.
Kennon-McGill: That’s huge. I mean, that would be a really great breakthrough, to be able to target that way and be able to take out the cancer without damaging the rest of the system. So this is the crux of your ARHVA project. This is what you’re really focused on, is developing radiation-activated liposomes to deliver things like cisplatin.
Jenkins: Yes, so we’re not trying to develop new chemotherapeutics and go through the horrific process that is FDA clinical trials. We’re trying to use things that are already approved, that have limitations. So cisplatin is a first-line therapy. Doxorubicin is another first-line therapy that we’re looking at, because we can use a different loading mechanism. But the crux of it is developing that correct lipid recipe to get the maximum response.
Schaffner: What current phase of your project, are you in as far as testing or, how far away are you from marketing and pushing it out? Is that too far out?
Jenkins: Depends on how the stars align. So if things go smoothly, we can get through in vitro and preclinical mouse testing in two years easily. If things go wrong, this could all be dead in the water. But if things go smoothly, I think we can be out the door in two years, with at least finding somebody to invest in it, to translate it further into the clinic.
Kennon-McGill: Is there anything else that you want to talk about in terms of whether there are any specific cancers that you’re hoping this could work on?
Jenkins: For right now, we’re looking at lung cancer as our model. And eventually it would be good to be able to look at more deep-seated tumors that are harder to treat, things like pancreatic cancer, liver cancer – anything really where you have problems cutting it out with a knife, and it’s deep enough that radiation is already going to be in use, because that radiation still has to be applied. And so this would be augmenting the radiation dose that’s already happening therapeutically in the clinic.
Kennon-McGill: Okay, just so I’m clear: so the radiation activation occurs after the liposomes are already delivered in the body?
Jenkins: Correct.
Kennon-McGill: Okay, I don’t know why I was thinking it was something that happened before they were delivered. This makes more sense. Then, if they’re already getting radiation, this is just like an added benefit.
Jenkins: So historically, a lot of the literature would tell you that you get a maximum tumor uptake of liposomes in about 24 hours. And so that works out really well from a clinical timeline. You come in, you get an infusion, come back the next day for radiation. And it’s not as good as doing it all at once, but it’s better than having a 12-hour timeline.
Kennon-McGill: Yeah. Okay, great.
Schaffner: So you mentioned difficult cancers, like pancreatic cancer. Is it difficult because the cancer itself is aggressive, and this treatment could potentially meet that aggression.
Jenkins: It’s a hard-to-treat cancer. It has a very high mortality rate and a very low remission rate. There are a lot of cancers – like breast cancer and lung cancer – where we’ve really been able to knock down the mortality, not me specifically, but the community at large. And there are others that are not really responding to the treatments that we’ve applied, and they still have a really high five-year mortality. And so those are the things that are harder to treat, and so being able to throw more at them without running into dose-limiting toxicities would be very beneficial.
Kennon-McGill: What are some of the things that you’re hoping to achieve in the short term on your path toward commercialization for this.
Jenkins: In the short term, I’d like to be able to get good in vitro and in vivo data so I’ve got good pre-clinical data that I can work with. I wouldn’t mind getting some other additional external funding. Once I can get that into place, I would really like to be able to demonstrate this on a library of compounds. The simple view of things is always you give chemotherapy to cancer, but the reality is you give a particular chemotherapy to a particular cancer, and so being able to swap in whatever you need to for whatever problem you’re dealing with would be extremely advantageous, and I think it would be a highly marketable feature.
Kennon-McGill: What do you view as the path to commercialization for this? What do you think needs to be done between now and actually getting it into the clinics and getting it to market?
Jenkins: Ex vivo, you would need to demonstrate radiation release, which we have some preliminary data that’s promising. And then from there, you would need to demonstrate that you can get it to collect in the tumor, you can get it to release in the tumor, and you have a reduction in off-target toxicities.
Kennon-McGill: You mentioned getting someone to invest in it, to kind of take over at a certain point. Where do you view that point as being? What do you expect to be able to do here, versus finding a partner or someone to license it?
Jenkins: I think we could do the small scale now study here, the n equals 10, the P value is less than 0.05, the real basic one. And then farm out to somebody, the “we did this with 100 mice” capacity people. And then if we can get the simple initial proof of concept, all good, and we can trade things out, then being able to get somebody with more funding to run the huge matrix of compounds and diseases – I think that’s where there’s real benefit for a corporate investment.
Kennon-McGill: Could you imagine starting a startup around this? It seems like something that would be good because you could test all these different compounds. I could see this being like a promising startup.
Jenkins: I could definitely see that being a direction that’s worth going. But at the same time, I would like to farm out all of the executive work and the paperwork and stuff like that. So,
Kennon-McGill: Yeah, we always talk about how what makes a good scientist doesn’t necessarily make a good CEO. What kind of next steps, future directions, do you envision?
Jenkins: One of the other long-term things is we want to be able to add targeting moieties so that we can direct specific interactions to specific cells. That should be able to further augment the efficacy and increase the amount of liposomal accumulation in the tumor.
Kennon-McGill: How do you add targeting moieties to something?
Jenkins: You have to find the correct lock and key, basically. And then, since the liposome is hydrophobic, you can use that hydrophobicity as an anchor whenever you’re in a water solution – oil and water kind of a thing.
Kennon-McGill: So how does your participation in the ARHVA program help you in achieving your goals?
Jenkins: ARHVA has been really helpful in that they’re responsive and they’re very flexible in how you can spend your funding. So if you get federal funding, it’s very rigid. It’s very regimented. I can spend three months trying to get $5 worth of washers from Lowes, whereas if we go through ARHVA, we can get it done in an afternoon.
Kennon-McGill: I’m happy to hear you say that, because that’s one of the biggest benefits that we want to be able to offer, so you aren’t bound by those restrictions with federal funding, and you’re also not having to go through 15 different people to get stuff. We want there to be as few roadblocks as possible for our inventors. That’s why we call it an accelerator: so we can get you to where you need to be faster.
Jenkins: It definitely allows for a lot more flexibility in what you want to do. It makes it a lot easier to find vendors that are not the standard vendors that are being used.
Kennon-McGill: So what other kind of funding are you looking for? You mentioned wanting to get more external funding.
Jenkins: I’m working on an R21 right now. That’s a two-year NIH grant. And if I can get a good amount of that put together, I’m hoping to work with Dr. Griffin, potentially, and some local companies to try get an SBIR, because that also gives you a lot of flexibility in how you spend your funding.
Kennon-McGill: And Dr. Griffin, for our listeners, is Rob Griffin. He’s our VP of small business concerns at BioVentures, so he’s great at working with faculty who want to explore entrepreneurship and commercialization. So glad to hear you’re thinking in that direction with Rob.
Schaffner: You know, you talked about next steps. We talked about the future outlook. At the end of the day, how far do you want to see this thing get? What is your ideal place for this project and this research to end up?
Jenkins: You mean when do I stop having to deal with it?
Kennon-McGill: [laughs]
Schaffner: Yeah, sure.
Jenkins: Well, I would like to see this implemented in the clinic, and I would like to see it reduce mortality for cancers. That’s why we’re doing this. For my from my point of view, I would be very content to get some intellectual property, to get it out the door, to get somebody with more resources, more funding, more time, more facilities, more connections, to get somebody else to do the filling-in-all-of-the-holes kind of labor. I’m perfectly happy to start the road, but I don’t want to fill in all the potholes.
Kennon-McGill: Yeah, I get that.
Jenkins: I mean, I will say that one of the advantages of ARHVA is – not just that they can do things externally to facilitate stuff – they’re also able to cover costs at UAMS cores, to do IDTs or interdepartmental transfers. And so they can facilitate things that are going on intramurally, as well as facilitating things that are going on with the broader planet Earth.
Kennon-McGill: [Laughs] Yeah. We’re trying to support you in any way that we can, and part of that is funding. If there’s somebody else who can do a part of your project, like one of the cores, then we want to be able to pay for that, because that is something that is going to help you, and they can do it faster than you trying to figure it out alone. So yes, I’m glad to hear that you’re taking advantage of that. All right. Well, thank you, Samir. We appreciate you being here today.
Jenkins: Thank you for having me.
Kennon-McGill: Great talking to you.
Schaffner: That’s it for today’s show. A very special thanks to Dr. Samir Jenkins for the good work he’s doing and for sharing his time with us. For more information about the AR Health Ventures Accelerator program, visit bioventures.tech. You can keep up with us on Facebook, X and LinkedIn. Feel free to reach out to us and let’s keep the conversation going.