Protein arginine methyltransferase 5

um but now we have 34 developmental candidates it says 31 here but we actually nominated three more since i updated my patch so many of those drugs are you know potential blockbusters so we also are going after drugs that are commercially viable and pharma likes things that are established The target is very well known.

I have pan-KRAS, I have APALYN, I have the PRMT5, next generation.

I have the NLRP3, several generations, including brain penetrant.

I've got QPCTL.

But like every other targetable drug, they're going to eventually develop resistance.

And that's... eventually where we run into trouble and so i'm really interested in figuring out um what are the next set of targets that you can give with targeted therapies that will extend the benefit from targeted therapies by targeting multiple things like directly together and so we have a couple hints of this in lung cancer there's um A group of lung cancers that have what's called MTAP deletion, and we have PRMT5 inhibitors.

That might be one way to do this.

You may be able to do this with ADCs and targeted therapies, although you have to be a little bit careful.

Yeah, I mean, the thing that I'm most hopeful about are these sort of like new, you know, I think that the success of KRAS and especially the success of the molecular glue, you know, so-called sort of tri-complex KRAS inhibitors, I hope has convinced drug discoverers that there's a lot of untapped chemical space out there that can make useful drugs for oncology.

And so what I'm most excited about in oncology in general is looking at these new drug modalities, looking at molecular glues, looking at protax, looking at rip tax, looking at new ideas in the chemical space that can unlock parts of lung cancer that were previously untargetable.

So MTAP, PRMT5 inhibitors are in a way or this, like some people have called these sort of lock attacks.

They lock a protein in a specific configuration.

And also, there are some other pathways in the cancer cell for which signaling is aberrant, and targeting that signaling with a RAS inhibitor has shown promise.

So for example, a class of drugs called PRMT5 inhibitors, they address MTAP loss, which is a gene that's involved in a metabolic pathway in pancreas cancer.

So all of this is kind of, you know, starting now to evolve rapidly.

And I think we hope the pace of change, you know, while it can't catch up for 20 years of historical modest progress, but it can certainly hopefully change very much in the next three to five years.