Michael is actually the Head and Director of research at his practice in Bakersfield, California. And importantly, he has been involved in multiple clinical trials for decades. And we have him here today to talk about a novel agent that's placed into the bladder to treat patients with bladder cancer.
If I have it right, this is actually a salmonella that's actually placed into the bladder to help treat bladder cancer. So tell us... First of all, welcome. And now tell us a little bit about what you're presenting at the AUA.
Michael Oefelein: You bet. Thank you for the invitation. I'm presenting the phase-one data on Prokarium's lead asset called ZH9, which is an attenuated form of salmonella. It's smartly engineered such that it maintains its invasive potential, and it's a very strong immunopotentiator, but it has replication controls built in and it doesn't cause systemic side effects or sepsis.
Sam Chang: Okay.
Michael Oefelein: And part of the novelty of this agent, it's such a strong immunopotentiator that, unlike BCG, one dose seems to be sufficient for immunopotentiation, because it induces the state of chronic bacteria, which self inoculates and stimulates the immune system.
Sam Chang: So tell us about the dosing, and tell us what you found in this phase-one.
Michael Oefelein: So it's intravesically dosed, it's simple to reconstitute, and it was a classic phase-one dose-escalation study. There was no dose-limiting toxicity and patients tolerated the investigational agent quite well. There were usual issues such as frequency and dysuria, but they're all mild grade.
Sam Chang: So no systemic fevers, toxicity associated with a salmonella-type infection then?
Michael Oefelein: No, none of that happened. It was very well-tolerated, and very safe.
Sam Chang: And so this medication is just given via catheter after you reconstitute it. So, any specific safety measures that you have to do separate, does it have to be chilled? Anything different from...
Because some of these agents we have now available require either a chilled storage, require certain types of safety characteristics because they're viral therapies, et cetera. This is more of basically it's reconstituted, it's given, and then that's it?
Michael Oefelein: Correct. It's like BCG in terms of the storage and safety issues. It's reconstituted. The labeling isn't, of course, done. We used a bio containment hood just for safety reasons, but it doesn't seem to be necessary because it's a closed system. Very easy to do.
Sam Chang: And the dosing schedule's once and then that's it? Once every few months? Because as a possible patient, the first thing you hear is you have one dose that may be equivalent to multiple doses of other therapies. It's quite impressive. So with the phase-one/phase-two, tell me about the dosing schedule then.
Michael Oefelein: So the dosing was a single dose, but then there was a protocol amendment to re-dose.
The single dose was dose-escalating from a low-colony forming unit to a higher-colony forming unit looking for dose-limiting toxicity and none was found. And then the protocol amendment allowed for re-dosing. I had, I think, about 10 patients I enrolled in the clinical trial, and I re-dosed almost all of them.
And it was not set in standard, there was no experimental design for predicting the best frequency of dosing. And we know from preclinical data it's a very strong immunopotentiator. And so, in general, it thought that one dose may be sufficient, but the sponsor wanted to see how patients reacted to re-dosing.
Sam Chang: To a second dose, absolutely. And so I know it's early, it's a phase-one/phase-two. Any efficacy data that you can share, will share with people here at the AUA?
Michael Oefelein: So the patients enrolled had to be recurrent and they were all high-risk, except for a few intermediate-risk patients, but they were generally heavily pretreated BCG-exposed, but recurrent in all aspects. And the results in my population, I'm not privy to the entire data set, but they did well. In patients that were highly recurrent, they had complete responses in most circumstances.
Sam Chang: So at least, just as many of our early trials are hypothesis-generating, it's exciting. You can never stick your head out too far in terms of, "Oh, this is the next best thing."
But you have an agent that is safe, that seems to be well-tolerated, no, really, dose-limiting kind of toxicity was found, and that at least with a schedule that is favorable for a lot of patients, you've got some efficacy. So it'd be very exciting.
So where do we go now? The trials enrolling, continue to enroll patients in the phase-two aspect. Where next do you think?
Michael Oefelein: The company will probably be doing a phase 2B study to establish efficacy, and the details of that are not known to me. The phase three trial, of course, would be the next logical step. If you think about, how do you design an intravesical therapy? You want it to be one and done if possible, as opposed to BCG, which is weekly, and then maintenance. And I think the fact that BCG is weekly and then requires maintenance just highlights that it's not a very strong immunopotentiator.
I think agents like we see here with ZH9 and the salmonella variant, and the Protara strep pyogenes, indicate the potential for a higher immunopotentiation exists and these newer intravesical antimicrobial, or microbial agents, might yield that, which may, in fact, reduce the need to have another checkpoint inhibitor or an accompanied therapy like pembro or whatever there is. So these are exciting possibilities.
Sam Chang: I think from a urologic surgery standpoint, to be able to avoid the systemic immunotherapy is very appealing, to have an agent that is on a dosing schedule that is minimal compared to BCG, or other chemotherapy options, appealing. So, we look forward to the upcoming data as you continue to enroll patients, and it expands, and hopefully we'll be able to talk to you again.
Michael Oefelein: I look forward to it, Sam.