Ras GTPase

And that condition is associated with an inborn error of metabolism for a different gene.

That's the HRAS gene, the HRAS.

Now, those patients that are usually found early in development, young children, have about a 15% lifetime risk, but not necessarily movement into a malignant tumor.

So keep that in mind.

And it develops subsequent, it's believed, by acquiring mutations.

Now, the kind of mutations you find that are acquired are fibroblast growth factor, FGFR receptor 3.

Of course, the rash genes like the HRAS may also come on board and the telomerase.

Well, the telomerase itself is known as a reverse transcriptase, obviously, because it uses RNA to regenerate DNA to generate the telomere.

40% of patients with pancreatic cancer have the MTAP deletion.

And we have discovered here at Tango that the combination of our drug, Vopimetastat, with Dyrexone RAS, which is a pan-RAS inhibitor, has a very high level of synergy.

And so the data that we presented at the ESMO conference, which you referred to, yielded an 82% response rate for the combination and second and third line pancreatic cancer.

We had 22 patients evaluable and have seen this 82% response rate.

So, your response rates are very impressive.

How do you know what is the contribution of each individual drug? So, for example, if...

If it was just Durex on RASM alone being tested, how do you believe the efficacy would look different than yours? And part of the reason I asked the question is in drug development, one thing we've seen with FDA lately is they ask for contribution of parts and having a good understanding of that.

So how are you thinking about that?

And when they are covalently bound to palmitic acid, that allows them to tether in the membrane.

So these are going to be stimulated kinases, some of which include the RAS family GTPases, the RAB family GTPases.

And these are directly involved as molecular motors for vesicular trafficking.

And the vesicular trafficking involves other proteins that facilitate the RAS and RAB GTPases.

And these include the proteins linked in the membrane known as syntaxins.

And syntaxins associate with other proteins called the SNAPs or the SNAP proteins.

KRAS mutated cancer broadly.

I think this is a very exciting first step, but then we also have the very focused piece, but then we have the very broad piece, which is the pan-RAS.

Yeah.

Yeah.

Right.

And you have the pan-KRAS, you have on and off, you know, there's so many different aspects of this that are, and there's still open questions.

How do we combine a pan-RAS with a focused RAS? Does that help us avoid escape mechanisms? We're going to see escape mechanisms, a more targeted drug.

Yeah.

New England Journal of Medicine, Dr. Abba et al.

Dyrexonracib, our favourite on-RAS inhibitor, now being used in previously treated RAS mutant non-small cell lung cancer.

and response rates of 30%.

But Chris would like the way this abstract was written because they mentioned the adverse events rates of grade 3 or higher first of 54%.

Duration of response was around 11 months median duration of response, but some responses up to 16, 17 months.

So it's a little bit me too in terms of the other RAS inhibitors in the lung cancer space.

I was expecting those rates to be higher.

I don't know what anybody else had a thought.