During early days of Revolution Medicine, when you started to hear these first few cases or results of patients responding to direxanracib in early phase trial, what was your reaction like? What were you thinking? What were you feeling at that time?

know important to keep in mind and i know you all understand this very well that you know for decades we thought of pancreatic cancer we've been taught by the experts in pancreatic cancer that it was invincible that the tumors were full of fibrosis the desmoplastic response that drugs wouldn't be able to get in that the tumors were just impervious to these drugs.

We were all taught that, and I practiced medicine in that way in the earlier part of my career.

But we did just follow the science, and the advent of the oncogene hypothesis, which emerged in the 1970s, even though at the time it was a hypothesis about cancer-causing genes in mice and rodents, it really wasn't about humans at the time, but the first human oncogene to emerge in 1982 was RAS.

And ultimately, some half a dozen years later, it became recognized that it was really the most common human oncogene.

And then eventually recognizing that in pancreatic cancer, More than 90%, in fact, I'd even argue it's probably closer to 95% of pancreatic cancer is caused by a mutated form of RAS.

And the other several percent probably fundamentally go through wild-type RAS as well.

Mark, were you in the crowd to witness all this, and what was your reaction like?

What's the, what's the size of that population?

Uh, thank you very much for having me on.

It's a real pleasure.

The approval of RASONQ is a monumental step forward for patients with metastatic pancreatic cancer.

We believe that RASONQ introduces a practice-changing targeted medicine that's well-positioned to become a new standard of care, which is a strategic priority for our launch.

It's the first targeted medicine, uh, that's approved in pancreatic cancer to inhibit its main cause, RAS, and it's shown superior efficacy compared to, uh, chemotherapy.

As to the patient population, there are roughly 55,000 new cases of metastatic pancreatic cancer, uh, each year in the United States.

Does this change, do you think, uh, the discussion around it in aggregate about it being so, so low surviv- survivability? I mean, how high can those numbers go?

And, you know, you've had these results for some time, and I just wonder what went through your mind when you first saw what, you know, what data you presented?

Yeah.

Well, thank you for having me on, Angelica.

This is a really important moment for patients who are living with cancers caused by RAS proteins, the most common, uh, cause of pro- of, uh, c- of human cancer.

Um, we are deeply committed to bold scientific innovation, uh, in our effort to revolutionize treatment for patients, uh, living with these very difficult to treat and, and common cancers.

Um, the emotions for us when we first saw those data were very high, just as they were in the room, uh, yesterday.

The results that were reported, uh, here at this conference yesterday for the RASlute 302 trial on pancreatic cancer were unprecedented, uh, with a 60% reduction in, uh, the risk of death for patients who were receiving draxirasin.

So do you think that the FDA would actually approve it for the first line without seeing those results?

Can you say anything about the timeline of filing for approval?

Yeah.

We, we feel very much the same urgency that patients and their families feel to get, uh, diraxsonrasib out and available to patients outside of, uh, clinical trials.

We are running many clinical trials, and some patients can participate in those, but to get the drug to patients who can't, uh, access a clinical trial, we did contact the FDA very shortly after we saw the early results.

We, uh, sought their advice about an expanded access program, applied for it, and they responded very quickly and gave us clearance, uh, with our, uh, expanded access protocol.

That effort is now fully operational.

Uh, and in fact, even this month since we received that approval, we're already shipping drug to doctors on behalf of patients who have been approved in the, uh, expanded access program, and I think that will continue to grow, uh, in the coming, uh, coming days and weeks.

Wow.