IL2RA

So there's a context-specific differentiation for cholesterol.

For example, the K9 convertase didn't affect CD25 expression despite reducing CD8 positive T cell proliferation.

So some proteins aren't affected by the k- because of substrate specificity.

But nevertheless, understand CD25 marks an interleukin-2 dependent component of activation.

So I told you before that cytokines act as modulators, activators of T cell activity.

They don't-- They're not just pro-inflammatory or anti-inflammatory.

Whereas proliferation requires a more sustained overall cohering metabolic activity, which includes glycolysis, the oxidative pentose phosphate turn, the electron transport chain in the mitochondria, as well as the TCA and the malate-aspartate shuttle and the glycerol three phosphate shuttle, all the principal players in anaplerosis as well for amino acid transamination reaction to see more complexity when you start reading out long term when you're looking at proliferation of cells.

So context dependence.

It's 19 by 3, whereas all of our currently commercially available ones, Mosonituzumab, Glofitumab, Epcritumab, Ojunixumab in Europe are all CD20 targeting.

It's been developed in the trial that you're describing as a single-agent multi-histology step-up dosing strategy, similar to what we use with our CD25 specifics.

And we've seen pretty impressive activity, both in large cell, but in my opinion, even more so in follicular lymphoma.

The large cell activity is good in a quite heavily pretreated patient population, including prior CD19 CAR-exposed patients.

Um, T regs express a high-affinity IL-2 receptor.

This is CD25, uh, the alpha receptor of the IL-2-- of, uh, the alpha subunit of the IL-2 receptor, and, um, they are very responsive to IL-2.

But of course, IL-2 also activates ac- other, other cell types, cytotoxic T cells, and other, uh, activated T cell populations.

Um, and if you wanna sustain Treg function by infusing IL-2, there is a limit to, to how much you can put before you start activating also the problematic T cells.

Uh, it's a bit kind of weak activation, but it's very specific.

So you can put a lot of the mutine, and it's not gonna activate, uh, T cells that don't express this receptor.

Um, but what they find is that although it works really nice in vitro, once you put the cells in mice and you inject the, the cytokine in the mice, it doesn't seem to help increase amount, number of Tregs or the, the expression of CD25 and FoxP3, which kind of a indicator of, of proper stimulation.

Um, so they don't protect of the mice, uh, for i-in a, um, diabetes type 1, uh, mouse model.

I credit it as being worthwhile as well.

Now, there is a DSA member, Oliver Larkin, who's running for CD25 in Florida.

Everybody who's in the same party is crazy now.

What does he say?

And that's the good thing about being a chair of the Florida Democratic Party is that I don't get involved in primaries.

But certainly what we're hearing, this CD25 has been redrawn.

intentionally to make this seat more difficult for Jared Moskowitz.

But the reality is that this is one of the most concentrated seats of Jewish voters in the entire country.