Phillip Koo:

So let's go on to the third trial called ARASAFE.

Zach Klaassen:

Yeah. So the ARASAFE trial is actually a really interesting trial design. We know we just talked about triple therapy from ARASEN and PEACE-1. It's interesting, part of that triple therapy is chemotherapy, and chemotherapy to men with metastatic hormone-sensitive prostate cancer can be a little scary. I think there's certainly a subset of men that still benefit from a triple therapy with chemo.

We've got lots of great double therapy options. We just talked about ARANOTE. But some people that come up with aggressive features right from the start, I think a triple therapy, hitting it hard three different directions right up front really has a benefit. And so chemotherapy is a scary term, but again, this is not chemotherapy until you die. It's not chemotherapy till we don't tolerate it anymore. It's six cycles of chemotherapy.

And so what this trial looked at is there different ways to give the chemo that may be a little bit more better tolerated than the traditional way we've done it? The traditional way we've done it, you can see the yellow here. This is docetaxel. The dose is 75 milligrams per meter squared every three weeks for six cycles. The experimental arm in this population was docetaxel 50 milligrams, so a little lower dose, but every two weeks, to sort of see is there a difference in adverse events. And you can see the primary endpoint was safety. And so this was just a hypothesis-generating trial to see if we could give chemotherapy in this population and maybe decrease some of those side effects.

And in fact, we did see that in this trial. The primary endpoint grade 3 to 5 adverse events was 78.9% in the traditional chemotherapy arm versus 61.2% in the experimental arm of 50 milligram per meter squared every two weeks. And this is statistically significant P-value. When we look at grade 3 to 4 neutropenia, which is decreasing white count or death, 64% in the docetaxel sort of traditional treatment versus only 24% in the experimental arm. And I think this sort of highlights again on the adverse events, looking at specifically just grade 3 adverse events, 40.6% versus 48.8%. So a little higher in this experimental arm. But when we get to grade 4, we see a significant reduction from 33.6% in the traditional chemotherapy assessment down to 9.1%.

So what this trial tells me is that we're getting the chemotherapy into the patient, in those appropriate patients for triple therapy, and maybe this new dosing regimens slightly better tolerated than how we've been doing it in the past.

Phillip Koo:

That's very interesting. I love this idea of challenging the way things have been done. So this idea of a lower dose of chemotherapy a little bit more frequently ends up having, in general, less adverse events. I guess the biggest question becomes, is it still clinically as effective as the standard chemo regimen? And what are your thoughts there, and when will we know those answers?

Zach Klaassen:

Yeah, it's a good question. I think that's really the main question. We know it's better tolerated. Okay, great. That's our primary endpoint. But some of those secondary endpoints, which are in that trial design, they haven't read those out yet. So, I think that'll be very important to follow this up because certainly we want better tolerability, but we really want it to work still. My gut feeling, and we'll see the data at some point, is that it probably will, but until it does, this is still in the experimental phase, and we'll sort of read this trial a little bit further.

Phillip Koo:

Great. So I guess the take-home for patients are if you are going to get that triple therapy, you sort of stick to the tried-and-true and we'll see what this data shows later on as more data is presented.

Zach Klaassen:

That's right.