Mark Garzotto: Thank you.
Phillip Koo: So you presented data yesterday on this trial. Before we get into the actual data, can you give us an overview of this novel drug that really meets an unmet need, particularly in localized prostate cancer?
Mark Garzotto: Yeah. So CAN-2409, also known as aglatimagene is a replication-deficient adenovirus that when introduced into cells, particularly cancer cells, it expresses an enzyme called thymidine kinase. And once thymidine kinase is in the cancer cells, it converts a prodrug called valacyclovir that the patients are taking orally. It converts that into a cytotoxic nucleotide. That cytotoxic nucleotide gets incorporated into DNA, particularly when there's DNA damage, like what happened in the trial with radiation. Radiation induces double-strand DNA breaks. Opportunistically, the valacyclovir is converted to the cytotoxic nucleotide. And when the DNA tries to repair itself, it incorporates this nucleotide. And that essentially stops further DNA synthesis and that leads to cell death in that tumor cell. So that's the primary mechanism.
The secondary mechanism, which has garnered a lot of interest is the immunologic response that's generated from this. We know that radiation helps that the tumor cells express more antigens. So to increase antigen expression and interact with T cells, but the adenovirus capsid proteins are thought to stimulate a local immune response to help recruit those T cells to the tumor microenvironment. So essentially, it's like a one, two punch. You hit it with the radiation and then you don't allow the tumor cells to repair themselves and you've got the secondary immunologic response.
Phillip Koo: Yeah, that's so exciting. So you inject this into the prostate, you give a prodrug, you do radiation, which I think is so exciting because it brings back this idea of immunotherapy to the prostate cancer space. So now you have an extended data cut. I believe it was March 2026.
Mark Garzotto: Correct.
Phillip Koo: So what are some of the new data points that you're seeing now that there's more follow-up data?
Mark Garzotto: Yeah. So with the new data cut, we've got an additional eight months of follow-up beyond what we had before. We're also looking more at, in this study, the prostate cancer disease-free survival to really focus on how effective the drug is. And so what we're finding is that with additional follow-up, we're seeing greater separation of the curves between the placebo arm and the aglatimagene or CAN-2409 arm.
Phillip Koo: So can you explain to us what this prostate cancer disease-specific survival endpoint is? I think it might be new to some of us.
Mark Garzotto: Yeah. So first off, these endpoints were agreed upon with the FDA in a special protocol assessment. And so this has been agreed upon at the initiation of the trial. It was reaffirmed later on. And so what it looks like, it looks at a composite of endpoints. It looks at metastasis, local recurrence, death from prostate cancer, but it also looks at one of the things that we incorporated, which has been found to be a very predictive biomarker for prostate cancer outcomes is the two-year prostate biopsy results. And so all the patients were recommended to have this two-year biopsy to determine whether there's eradication of tumor. And so that turned out to be, in this trial, very useful for predicting clinical outcomes. It's being used more often in trials. I've seen it come up several times. So I think it's something that is going to be a marker that helps give us a very early predictive biomarker that allows us to tell a patient whether or not they're destined to recur development tests and even die of prostate cancer.
Phillip Koo: That's really interesting. I know you mentioned the follow-up biopsies. Can you share with us what was seen with a lot of those follow-up biopsies?
Mark Garzotto: Yeah. So there is a paper from the original presentation that's coming out in press very soon. And the data showed in that paper that the difference in the biopsies, it was around 80% negative biopsies in the CAN-2409 aglatimagene arm, but only about 60% in the placebo. You have to remember, this is a blinded study. So the pathologists were blinded to the outcome. All the investigators were blinded to the drug that was received versus placebo. And the investigators were obviously blinded as well.
Phillip Koo: I think that's fascinating. It's so exciting to see that pathologic response as well. So now we have this novel drug localized prostate cancer. Clearly it's showing over time, greater time, even a greater impact on prostate cancer disease-specific survival. Let's take a step back and think about from your perspective, what does this mean potentially for patients across the world?
Mark Garzotto: We know that among patients who undergo radiotherapy, at least 30% are going to recur with long-term follow-up. And those patients, when they recur, they ultimately wind up getting primarily lifelong hormonal therapy, but there are other salvage therapies that can be done. None of them are proven to prolong survival. Things like HIFU, cryo, surgery, other things can be done, but these patients are going to wind up with long-term side effects from their treatment. And what this does, it holds the promise of potentially reducing that by what we showed in terms of disease-free survival by 40%. That holds the promise of being given a greater chance for being cured with your first treatment. Because we know that in oncology, in almost every disease state, your best chance is your first chance. And so we're trying to optimize the patient's chances to achieve a long-term remission at the get-go so that they have less worry about ultimately being put on lifelong hormonal therapy and having to deal with complications of salvage therapies.
Phillip Koo: That really is so exciting because when you hear that statistic of 30 to 40% of patients having biochemical recurrence after definitive therapy, you clearly see that there's an unmet need and a huge opportunity to increase cure rates. So, so, so exciting. Really, really grateful that you were here to present this data and share it with all of us in the UroToday community, so thank you.
Mark Garzotto: Thank you.