NPM1

So we know that acute myeloid leukemia, despite the fact that it is increasingly common in our older patients, is an amazingly diverse disease, meaning that all patients coming in with AML do not have the same type of acute myeloid leukemia.

So we know that, for example, about a third of patients that have acute myeloid leukemia are going to have a mutation in this gene called nucleophosphamine 1 or NPM1.

Patients that have that particular mutation are eligible for standard upfront therapy, but in the relapse refractory setting, those patients have a poor survival with overall response rates of 10 to 20% and survival that's in weeks to maybe a few months.

For patients with AML that has an NPM1 mutation, the leukemia is driven by an abnormal genetic program.

That program is controlled by what's called a master transcriptional complex.

This complex helps regulate which genes are turned on and which genes are turned off.

We know how to manage the side effects.

We currently have... probably three or four trials of the drug in different settings, and we are collaborating with other centers to open additional combination trials of this drug.

So they could be less than 60, as long as they did not have those types of leukemias that we think we can cure with just chemotherapy.

So core binding factor leukemia is NPM1.

If you're over the age of 60, you could be NPM1 positive.

No FLT3 patients at all.

And if you're over 60, you had to be, you know, fit enough for 7 plus 3 or CPX351 because that's the intensive chemo arm at 7 plus 3 or CPX351.

However, more than half the people in the study did have AML with myelodysplastic relay changes, which probably explains for the CPX351 benefit.

About 13% total had favorable risk based on the European Leukemia Net Favorable Risk AML.

Again, we're not including folks that have core binding factor leukemias or NPM1 if they're less than 60.

And we did that academically, but perhaps you could produce a diagnostic.

In the case, as you mentioned, we found that NPM1 which is actually a cancer-associated RBP, it's upregulated in cancer, inside the cell, is also upregulated on the cell surface.

And so there's an interesting opportunity to expand the suite of antigens or targets that could be applied to all of these modalities that have been expanded for cell surface proteins And rather than only targeting transmembrane proteins or receptors, we could perhaps also target the RNA biology, including RNA binding proteins.

And so that becomes a very interesting thing to consider.

With NPM1 being unexampled, there are others actually that have been more recently described or described when we were also working on that that have been moving forward in research.

in CAR-T format or in ADC format.

And so I think really we sort of, I think our interest is better understanding how cells present or literally express their state on the surface.