And so, basically, when you start to look at the profiles and start to map out what those different response profiles are, and then compare them to also we disclosed on what we call upset plots, which are basically projections of the molecular characteristics that align with those models and patients, that you see the broadest single monotherapy response potential in KRAS pancreatic cancer, and then RAS melanoma. We also see very promising single agent monotherapy potential in KRAS mutant lung cancer as well as KRAS mutant colorectal cancer.
Benjamin Zeskind: Thanks, Brett. And I would just emphasize, Jeff, this is a really unique and proprietary capability that we have. So the 3D tumor growth assays, this is a proprietary assay that we have up and running at our labs in San Diego. And we highly encourage everyone to schedule time to come visit those labs. We give a great tour. Second only to Disney Land in popularity in Southern California, but it really enabled us to very broadly assess the response profiles of different mutational profiles. And that proprietary view, I mean, 132, right, how many companies that have run 132 models on their lead program. And then that really ties in elegantly with all the deep informatics capabilities that we’ve developed over the last 15 years to create these plots that Brett described, where we’re actually projecting onto patient populations using real patient data to really identify and prioritize, which indications we think to kind of go after first.
So, it’s really a €“ it’s a platform that I think is very unique to Immuneering that we’re quite proud of.
Jeffrey Hung: Great. Thanks so much.
Benjamin Zeskind: Thank you, Jeff. Next question, please.
Operator: Thank you. One moment to our next question. Our next question comes from the line of Mark Breidenbach from Oppenheimer.
Mark Breidenbach: Hey, good afternoon. Thanks for taking our questions. This first one kind of goes back to something Ben mentioned, this is a drug that acts on MEK, which is of course downstream from RAS. I guess, I’m finding myself wondering why we should be at all surprised that activity you’re observing is independent of specific RAS mutations, shouldn’t that be the case for any MEK inhibitor? Or is there something different with this one? And the second question is just with regard to the timing of initiation of expansion cohorts. We’re talking about identifying a recommended Phase 2 dose by middle of next year, can we assume that’s a prerequisite before initiation of expansion cohorts? Thank you.
Benjamin Zeskind: Hey, Mark. Thanks for the question. So, you’re right. In theory, MEK has always been a great target, right. But it really hasn’t lived up to its potential yet. And I think, really, that’s because the first generation MEK inhibitors really had 2 main challenges. Number one, they’ve been limited mainly to RAS-mutant disease. And, secondly, they’ve really been quite toxic, very, very poorly tolerated. And I think that’s really in part, because they’ve all been developed in this same old chronic inhibition paradigm, where you shutdown the pathway 24/7, you maintain chronic occupancy, you maintain a drug trial, you’d never let the drug €“ the level of drug get close to zero. And, again, the problem is healthy cells need the MAP kinase pathway to.
And so, these first generation MEK inhibitors really just kind of harm or create challenges for the MAP kinase pathway and healthy cells. And so, I think that combined with the fact that they’re also all susceptible to a feedback loop, called CRAF-bypass that makes it really challenging to go after RAS-mutant disease. And so those were some of the design choices we made in creating 104. We gave it the ability to block CRAF-bypass. We gave it the ability to call them manyfold higher CMAX to really hit the tumor hard. And then we gave it a very short half life. So we’ve consistently said we projected 2-hour half life in humans. And the combination of those things gives us essentially the ability to hit the tumor hard, but then allow the pathway to reset, it really the idea that as I said earlier, every day is a drug holiday for the healthy cells, and yet every day is a judgment day for the tumor.
