So we're gonna start out talking about that.

All right.

So, um, over the next few minutes, I'll cover the PROTEUS data, the EMBARC data, and the PRESTO data.

And, uh, we'll have a conversation and share some patient, um, pearls.

So this schema is well-recognized by all of you and, uh, has held up over the, the decades.

And tonight, we're gonna be focused on the left part, uh, patients with localized prostate cancer and PSA recurrence after local therapy.

And we all know that these are heterogeneous, uh, patients within these stages of prostate cancer.

And Mark.

So we're gonna start out talking about that.

All right.

So, um, over the next few minutes, I'll cover the Proteus data, the Embark data, and the Presto data, and, uh, we'll have a conversation and share some patient, um, pearls.

So this schema is well-recognized by all of you and, uh, has held up over the, the decades.

And tonight, we're gonna be focused on the left part, uh, patients with localized prostate cancer and PSA recurrence after local therapy.

And we all know that these are heterogeneous, uh, patients within these stages of prostate cancer.

And tonight, we're really gonna be focused on the patients with localized high-risk prostate cancer and the patients who have a rising PSA, who have a short PSA doubling time.

And Mark.

So we're going to start out talking about that.

All right.

So over the next few minutes, I'll cover the Proteus data, the Embark data, and the Presto data.

And we'll have a conversation and share some patient pearls.

So this schema is well recognized by all of you and has held up over the decades.

And tonight, we're going to be focused on the left part, patients with localized prostate cancer and PSA recurrence after local therapy.

And we all know that these are heterogeneous patients within these stages of prostate cancer.

Thank you, Neil.

Would you like to tell us why you decided on these two with dual primary endpoint? And then tell us what were the main results, the main findings?

We chose a dual primary endpoint of an early readout, which we've termed major pathologic response, and a later endpoint, metastasis-free survival, because, of course, in the U.S., the FDA requires metastasis-free survival, which has been validated to correlate with overall survival.

Our hope would be eventually that we would be able to validate that a major pathologic response correlates with MFS.

So future trials could read out, you know, earlier than six or seven years.

So the results for the apalutamide and ADT compared to the placebo and ADT control were positive for both primary endpoints.

So there was an almost tenfold improvement in major pathologic response measured by having no tumor or less than five millimeters of tumor.

And there was an investigational response of looking at major pathologic response by what's called residual cancer burden response.

Yeah.

We start in prostate cancer with Mary Ellen Taplin, who presents final analysis data from the Proteus style, a pivotal study examining perioperative apalutamide plus ADT versus placebo plus ADT in patients with high-risk, localized, or locally advanced prostate cancer undergoing radical prostatectomy.

So the Proteus trial had two primary endpoints and a series of secondary endpoints and a couple very important exploratory endpoints.

So the two primary endpoints for Proteus were the pathologic response of the tumor at the time of prostatectomy.

That's an early endpoint.

And an endpoint called metastasis-free survival, which is a measure of the patients who develop metastasis or die.

In this event, metastasis-free survival was compared in the two groups.

The two groups were apalutamide and ADT.

Do you think the lack of clinical effect was just related to the systemic therapy used, i.e. this is obviously before the ARPI era?

Yeah.

I think it was related to two things.

I think it was related to having a lot of Gleason 6.

Most of these trials, half of the patients had Gleason 6 cancers.

We don't even treat those anymore.

And the other was lack of...

the answer to all of your questions.

And Mary Ellen, talk us through the, the main headline results that you presented today.

Sure.

I'd be happy to.

So I like to think of it as, uh, you know, the co-primary endpoints, major pathologic response, and metastas- metastasis-free survival, MFS.

So I like to think of it as an early endpoint and a late endpoint.

So the early endpoint of the pathologic response, we measured in two ways really.

The, the primary endpoint was based on a, a composite of PCR, pathologic complete response, and what we call minimal residual disease, which was one to five millimeters of residual tumor.

There's been speculation of why and can we really change practice if it's not standard of care, and I, I defended it in the discussion, but tell us your own thoughts on why was it chosen and what your thoughts are.