Joel Beatty: Great. Thank you.
Operator: Thank you. And our next question is from Noah Eisenberg with JPMorgan. Your line is open.
Noah Eisenberg: Hi guys, this is Noah on for Eric. Thanks for taking our question. Just kind of looking at the second line randomized trial for 8444 noticing that you’re stratifying by KRAS status. So based on that, we’re wondering is there any synergistic potential between DR5 activation and EGFR inhibition? And to what extent are you interested in evaluating EGFR combos or KRAS inhibitor combinations as part of the development strategy? Thank you.
Chris Takimoto: So maybe, I can start, obviously, the colorectal cancer space, there are €“ there we’re starting to see molecular profiling obviously have a big treatment impact on different treatment options. But one of the things that’s been very clear to us at least pre-clinically and also thus far in the clinic is that through our mechanism, we think we should work well in a variety of different molecular subtypes. So KRAS wild-type, KRAS mutant, we expect and what we’re seeing so far, again, small numbers and we’ll obviously look at this further, but we don’t expect to see really any differences in terms of just we expect to be active in all those subpopulations. That being said, as we think about really having a maximal impact on this disease and where do we go if we can confirm the signal and then where else do we go?
We would obviously be open to exploring other combinations in this space as we start to broaden the program. But at least the development and plans now is to try and go more broadly across different molecular subtypes. And I don’t know, there was kind of a mechanistic question there that maybe you can
Bruce Keyt: Yes. No, it’s a very good question. It’s a certainly an active area of research. We €“ as Chris mentioned, we haven’t seen differences due to KRAS positive or negative but there could likely we’d work in both, but the opportunity to combine is still a €“ is a good opportunity we’re investigating pre-clinically.
Noah Eisenberg: Thank you.
Operator: Thank you. And our next question is from Brian Abrahams with RBC Capital Markets. Your line is open.
Leonid Timashev: Hey, guys. Thanks. It’s Leo on for Brian. I had maybe a couple on the pipeline. So maybe starting with IGM-7354. Can you talk about given the initial clean safety data there in two patients? Is this a dose you think could be active? And then, I guess, when do you think we may get to doses where we’ll have more activity. And where’s the preclinical data steering you in terms of what doses you want to reach, what tumor types might be most active. And do you think you can also target low PD-1 expressing cells or is your strategy still going to be enrich? And then I had maybe a follow-up on IGM-2644 as well.
Fred Schwarzer: Chris, you want to take the €“ that question?
Chris Takimoto: Yes. So obviously, one of the things we do when we start a Phase 1 study is we €“ based on the preclinical data, make estimations of where we think efficacious exposure level is. And obviously for safety reasons and things in a dose escalation study, you generally start low and escalate. But I will say that €“ so in terms of our expectation going into the study, we would’ve that maybe in dose Cohort 3 or 4, we would be sort of entering the range that we saw clear actions in preclinical models. But I think the other factors that IL-15 is a potent agonist and we’ve shown certainly our molecules have been able to hit the target. So the safety we think is good, but we’re also through our biomarkers looking at pharmacodynamic effects even at the lowest dose levels.
And I think we’re off to a good start and we’ll have more to talk about in the future about this. But there is certainly the potential that we could start seeing evidence that we’re hitting the target even at the lowest dose levels in the study.
