Dr. Susan Galbraith

And we showed an improvement in the overall intention to treat patient population.

just as ever has done.

And the hazard ratio that we showed compared to the previous standard care for Western was good in that ITT population hazard ratio of 0.78.

And then the hazard ratio in the patients that are particularly sensitive to a SIRD

The patients that have got a mutation in the estrogen receptor, so-called ESL1 mutation, for those patients, we had a hazard ratio of 0.33.

So I think the camisestrant data compares very well with what has been seen with duodestrant, the ocean molecule in the Evera study.

But even in the wild type population in second line, those patients are still less endocrine sensitive than patients that have got newly diagnosed metastatic disease in the first line.

And that's the patient population that the Serena 4 study is aiming to improve.

There, the design of that study is a combination of camisestrin with a CDK4-6 inhibitor compared with standard of care, which is an aromatase inhibitor

with a CDK4-6 inhibitor.

And if you think about the comparison of the mechanism of action of camisestrin or oral SIRT with an aromatase inhibitor, an aromatase inhibitor actually reduces the circulating level of the ligand, the estrogen.

It's in the peripheral circulation that binds to the estrogen receptor.

It does nothing about antagonizing that transcriptional signaling downstream of the estrogen receptor, and it does nothing about the overall level of estrogen receptor.

Whereas the SIRD has two mechanisms of action, both inhibiting folly and reducing the level of the poison.

So it becomes

insensitive to the amount of ligand that's there, and therefore you get an improved activity.

And this is in a patient population that is more endocrine sensitive.

So although the vast majority of patients in that first-line metastatic setting do not have any SR1 mutation,

During the course of first-line therapy, it goes from 5% of patients to 35% to 40% of patients during that course of treatment develop an ESR1 mutation when they're on aromatase inhibitor.

And what we have already shown with the Serena 6 data is that when you treat patients that have got an ESR1 mutation,