James Byrne: Dr. Kamat, thank you so much for the invitation to join and to talk about this technology. So I'm a physician-scientist and radiation oncologist at the University of Iowa. I primarily treat patients with bladder and prostate cancers. My lab designed a new technology to make things easier for patients with high-risk non-muscle-invasive bladder cancer, and we called it DRIFT or Drug-Releasing Intravesical Floating Technology. For decades, and I think that the group really is well aware of this, intravesical BCG was the standard for high-risk non-muscle-invasive bladder cancer. However, a substantial fraction of patients are BCG-unresponsive, or many are either poor surgical candidates for cystectomy, or strongly wish to avoid bladder removal. So by the early 2010s, there were limited effective salvage options. Given this, Mike O'Donnell and his team at the University of Iowa investigated a gemcitabine-docetaxel regimen. And they found that in BCG-unresponsive non-muscle-invasive bladder cancer, there was a higher response rate to that gem-doce regimen. And so then they started to look at other areas within non-muscle-invasive bladder cancer where it could be useful. For the gem-doce regimen, it is pretty time-intensive for both patients and clinicians administering it, where these patients receive a Foley catheter, have the gemcitabine instilled, and wait for one to two hours, whereby the drug is then removed, and docetaxel is then instilled, and the patients will wait for a few more hours afterwards before removal.
We wanted to make the system a little bit easier on patients by administering the gemcitabine and docetaxel at the same time, but with docetaxel in a floating catheter delivered via Foley catheter. The device itself or the Foley catheter is subsequently removed so that patients would be exposed to gemcitabine first, urinate it out, and then be exposed to docetaxel from the device at a designated time. After deployment of the drug from the device, the device could be easily removed by the patient. So we created the DRIFT Technology with a goal of improving the care experience for patients receiving the gem-doce regimen. The DRIFT device is a small, flexible system that holds the docetaxel chemotherapy in a balloon. It's easily placed into the bladder through a standard Foley catheter, and it floats freely in the bladder without causing obstruction, so it floats away from the bladder neck.
The device's coded endcap dissolves slowly to release the docetaxel on a controlled schedule so the drug is delivered into the bladder after the gemcitabine has had its effect and been urinated out. After the device is inserted in the clinic, the patient would be free to go about their normal daily activities. And when the treatment is finished several hours later, the device could be easily removed by the patient at home via small string attached to the device. We tested the effectiveness of the DRIFT device in large animal models and demonstrated that it reliably contains the docetaxel chemotherapy during the two-hour or one-hour gemcitabine pretreatment period before it's released and releases the docetaxel into the bladder. With that, I'd like to thank my team at the University of Iowa, including Mike O'Donnell. I especially like to thank Vig Packiam, a urologist, urologic oncologist at Rutgers, who I created this device with. And then as well as thanking the many funders or collaborators that we have across multiple institutions and the funding bodies that generously support our work.
Ashish Kamat: Thanks so much, James. Really exciting to see this technology being developed. I'm sure you're familiar with the TAR-200 device, which obviously can release gemcitabine and other agents such as erdafitinib. But clearly that requires certain gradients, osmolarity, and it's a whole machinery behind it. Works really well. And full disclosure, we've had several people on this forum, and I'm part of the group that is part of J&J's executive team as well. But a device such as this that you guys came up with more of a, "We need this, let's do something about it." Tell us a little bit about how that thought process went about, more for folks that are listening and say, "Hey, we'd like to do something like this." How would you describe that process?
James Byrne: So it was an interesting process. And Vig Packiam, who is a fantastic urological oncologist that I worked with and treated many patients with previously, he and I were looking at different problems that he was facing with a number of his patients. And we started to look at creative solutions to try and address it. And so the inspiration from this system, actually, in fact, came from water balloons. And so, I have three boys. We enjoy a lot of activities outside. And water balloons, being one of them, we ended up considering and thinking about the way that these rapidly-deployable water balloons where you can hook it up to a faucet, get about 35 to 40 balloons popped out at a single time, used that, actually, as inspiration and the concept behind the device of DRIFT. And then have a fantastic team at the University of Iowa, been able to really take this to completion and showcase its use. And so I think it really happened over the course of really discussions with Vig and then bringing in some creative solutions that we could take inspiration from what you'd find out really outside of medicine.
Ashish Kamat: Yeah, that's great. At Iowa, you guys have had a bladder cancer powerhouse so many years. Obviously Michael O'Donnell, and then Ian, and Vig, and now we have Amanda who joined you guys, so it's a great group over there. And I'm glad that you're able to collaborate and come up with such ideas. Tell us a little bit about how exactly or where you plan to take this next.
James Byrne: So the hope is to try and really take those next steps into patients. Right now, the working idea is to start up a company and then potentially get non-dilutive funding through SBIR when the SBIR mechanism opens back up, but that's our hope. But either that or we would love to license it out to a company if we can't go down the route of starting it up as its own company and entity.
Ashish Kamat: Well, I'm sure companies will be listening to this episode, so you might be getting some phone calls. Along those lines, though, how do you control, because I know you briefly touched upon this in the paper as well, and you showed some of the animal models, but how do you exactly control for inadvertent leakage stability, at least in the animal model?
James Byrne: So it was relatively easy. There are two parts to the system that are open. One is a silicon endcap that we allow for drug filling while it's in the bladder into the device. And that pulls out, and so that will self-heal and close up. And then there's an opposite side or another side to the device itself that has a degradable polymer that over the course of a predefined time, whether it be 10 minutes, six hours-plus, we're able to, and it really dictated by the thickness of that biodegradable, bioabsorbable material, it will dissolve away and then allow for the drug to be delivered directly into the bladder fairly quickly. And we're able to find, really, the use of either an elastic material, whether it be silicone or others that are able to control and allow for expulsion of the drug fairly quickly.
Ashish Kamat: So the variables such as hydration status of the patient, urinary pH, are those relevant or is this independent of those variables, the dissolution rate?
James Byrne: Generally independent of those. So we can dictate and use bioresorbable polymers that really are pH-dependent or pH-independent as well as hydration status-dependent or hydration status-independent.
Ashish Kamat: Great. And again, it's early stages, so I don't want to put you too much on the spot. Clearly, something like this needs to be taken into humans, and then tested out, and seen. Do you foresee that this is something that could eventually incorporate both drugs in some fashion? You just put it in once and it releases the first drug exam. And then after a while releases the second one, docetaxel?
James Byrne: Totally. I think that we had envisioned this really as a grape-on-the-vine-type strategy where you could have one drug in one balloon, another drug in a second balloon, and then have it at defined release kinetics where you deliver one and then it'll deliver another at a predefined time. But there's a lot of opportunities to have multiple of these devices in place that can be easily removed by the patient.
Ashish Kamat: Great. I always say bladder cancer is one of those truly multidisciplinary cancers. And here, this is a prime example. We have a radiation oncologist who's doing intravesical drug delivery. So congratulations.
James Byrne: Thank you.
Ashish Kamat: Thanks for taking the time.
James Byrne: Of course.